AzTrials
AzTrials

HIV InfectionsPhase 3ATLAS-2MNCT03299049

Efficacy, Safety and Tolerability Study of Long-acting Cabotegravir Plus Long-acting Rilpivirine (CAB LA + RPV LA) in Human-immunodeficiency Virus-1 (HIV-1) Infected Adults

A Phase 3 study testing Cabotegravir Tablets, Rilpivirine Tablets and Cabotegravir Injectable Suspension in people with HIV Infections, run by ViiV Healthcare at 119 sites in 13 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This Antiretroviral Therapy as Long Acting Suppression every 2 Months (ATLAS-2M) study is designed to demonstrate the non-inferior antiviral activity and safety of CAB LA + RPV LA administered every 8 weeks (Q8W) compared to CAB LA + RPV LA administered every 4 weeks (Q4W) over a 48-week treatment period in… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV Infections
What is being tested?
Cabotegravir Tablets, Rilpivirine Tablets and Cabotegravir Injectable Suspension
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,049 participants
Where
119 sitesin 13 countries
Study dates
27 Oct 2017to 31 Dec 2029
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects who will be able to understand and comply with protocol requirements, instructions, and restrictions.
  • Understand the long term commitment to the study and be likely to complete the study as planned
  • Be considered as an appropriate candidate for participation in an investigative clinical trial with oral and intramuscularly injectable medications (e.g., no active substance use disorder, acute major organ disease, or planned long-term work assignments out of the country, etc.).
  • Aged 18 years or older (or >=19 where required by local regulatory agencies), at the time of signing the informed consent.
  • A female is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotropin (hCG) test at screen and a negative urine hCG test at Randomization), not lactating, and at least one of the following conditions applies:
  • Non-reproductive potential defined as: pre-menopausal females with one of the following: documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; Documented Bilateral Oophorectomy.
Show all 17Show fewer
  • Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to laboratory reference ranges for confirmatory levels)]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment.
  • Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication, throughout the study, for at least 30 days after discontinuation of all oral study medications, and for at least 52 weeks after discontinuation of CAB LA and RPV LA. The investigator is responsible for ensuring that participants understand how to properly use these methods of contraception.
  • Capable of giving signed informed consent. Eligible subjects or their legal guardians (and next of kin when locally required), must sign a written Informed Consent Form before any protocol-specified assessments are conducted. Enrollment of subjects who are unable to provide direct informed consent is optional and will be based on local legal/regulatory requirements and site feasibility to conduct protocol procedures.
  • Subjects enrolled in France must be affiliated to, or a beneficiary of, a social security category.
  • Subjects receiving oral SOC treatment for HIV-1 (not participating in ATLAS Trial) must be on uninterrupted current regimen [either the initial or second anti-retroviral (ARV) regimen] for at least 6 months prior to Screening. Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability/safety, access to medications, or convenience/simplification, and must NOT have been done for treatment failure (HIV-1 RNA >=400 copies/mL).
  • For subjects receiving oral SOC treatment for HIV-1 (not participating in ATLAS Trial) Documented evidence of at least two plasma HIV-1 RNA measurements <50 copies/mL in the 12 months prior to Screening: one within the 6 to 12-month window, and one within 6 months prior to Screening.
  • For subjects receiving oral SOC treatment for HIV-1 (not participating in ATLAS Trial): Plasma HIV-1 RNA <50 copies/mL at Screening
  • Subjects transitioning from 201585 (ATLAS) must have been on CAB LA 400 milligram (mg) + RPV LA 600 mg Q4W or "Current ART" regimen through at minimum Week 52 of the ATLAS study as per ATLAS protocol dosing requirements and until Day 1 of the ATLAS-2M study. Any disruptions in dosing during ATLAS must be discussed with the Medical Monitor for a final determination of eligibility.
  • For Participants transitioning from 201585 (ATLAS): plasma HIV-1 RNA <50 copies/mL at Screening Sub-study inclusion criteria
  • Eligible participants must have been on CAB LA + RPV LA regimen for a minimum of 152 weeks while on the ATLAS-2M study.
  • Plasma HIV-1 RNA <50 c/mL at Sub-Study Screening

Who cannot join

  • For subjects not transitioning from 201585 (ATLAS):
  • Within 6 months prior to Screening, any plasma HIV-1 RNA measurement >=50 copies/mL
  • Within the 6 to 12-month window prior to Screening, any plasma HIV-1 RNA measurement >200 copies/mL, or 2 or more plasma HIV-1 RNA measurements >=50 copies/mL
  • Any drug holiday during the window between initiating first HIV ART and 6 months prior to Screening, except for brief periods (less than 1 month) where all ART was stopped due to tolerability and/or safety concerns.
  • Any switch to a second line regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to therapy (defined as a confirmed plasma HIV 1 RNA measurement >=200 copies/mL after initial suppression to <50 copies/mL while on first line HIV therapy regimen)
  • A history of use of any regimen consisting of only mono or dual HIV-1 therapy (even if only for peri-partum treatment). Subjects who are currently participating in or anticipate to be selected for any other interventional study with the exception of the 201585 (ATLAS) study.
Show all 52Show fewer
  • For Subjects transitioning from 201585 (ATLAS):
  • During participation in ATLAS, consecutive (2 or more sequential) plasma HIV-1 RNA measurements >=50 copies/mL
  • During participation in ATLAS, any HIV-1 RNA measurement >=200 copies/mL
  • More than two total measurements of plasma HIV-1 RNA >=50 c/mL during participation in the ATLAS trial will require direct approval by the ATLAS-2M Medical Monitor and Study virologist for study participation.
  • For all subjects:
  • Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study.
  • Any evidence of a current Center for Disease Control and Prevention (CDC) Stage 3 disease except cutaneous Kaposi's sarcoma not requiring systemic therapy and CD4+ counts <200 cells/µL are not exclusionary.
  • Subjects with moderate to severe hepatic impairment.
  • Any pre-existing physical or mental condition (including substance use disorder) which, in the opinion of the Investigator, may interfere with the subject's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the subject.
  • Subjects determined by the Investigator to have a high risk of seizures, including participants with an unstable or poorly controlled seizure disorder. A subject with a prior history of seizure may be considered for enrollment if the Investigator believes the risk of seizure recurrence is low. All cases of prior seizure history should be discussed with the Medical Monitor prior to enrollment.
  • All subjects will be screened for syphilis (rapid plasma reagin [RPR]). Subjects with untreated secondary (late latent) or tertiary syphilis infection, defined as a positive RPR and a positive treponemal test without clear documentation of treatment, are excluded. Subjects with a false positive RPR (with negative treponemal test) or serofast RPR result (persistence of a reactive nontreponemal syphilis test despite history of adequate therapy and no evidence of re-exposure) may enroll after consultation with the Medical Monitor. Participants with primary syphilis or early latent secondary syphilis (acquired within the preceding year) who have a positive RPR test and have not been treated may be treated during the screening period and if completion of antibiotic treatment occurs during the screening period, may be allowed entry after consultation with the Medical Monitor. If antibiotic treatment cannot be completed before the screening window ends, subjects may be rescreened once following completion of antibiotic therapy for primary or early latent secondary syphilis.
  • Subjects who, in the investigator's judgment, pose a significant suicide risk. Subject's recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk.
  • The subject has a tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions.
  • Evidence of Hepatitis B virus (HBV) infection based on the results of testing at Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antibody (anti-HBs) and HBV deoxyribonucleic acid (DNA) as follows:
  • Subjects positive for HBsAg are excluded; Subjects negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded. Note: Participants positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not excluded.
  • Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not be excluded, however Investigators must carefully assess if therapy specific for HCV infection is required; participants who are anticipated to require HCV treatment within 12 months must be excluded. (HCV treatment on study may be permitted post Week 52, following consultation with the medical monitor).
  • Subjects with HCV co-infection will be allowed entry into this study if: liver enzymes meet entry criteria; HCV Disease has undergone appropriate work-up, and is not advanced, and will not require treatment prior to the Week 52 visit. Additional information (where available) on participants with HCV co-infection at screening should include results from any liver biopsy, Fibroscan, ultrasound, or other fibrosis evaluation, history of cirrhosis or other decompensated liver disease, prior treatment, and timing/plan for HCV treatment; In the event that recent biopsy or imaging data is not available or inconclusive, the Fib-4 score will be used to verify eligibility: Fib-4 score >3.25 is exclusionary; Fib-4 scores 1.45 - 3.25 requires Medical Monitor consultation; Fibrosis 4 Score Formula:
  • (Age x AST ) / ( Platelets x ( square [ ALT ])
  • Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).
  • History of liver cirrhosis with or without hepatitis viral co-infection.
  • Ongoing or clinically relevant pancreatitis.
  • Clinically significant cardiovascular disease, as defined by history/evidence of congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease.
  • Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study medical monitor for inclusion of the participant prior to randomization.
  • Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to receive study medication.
  • History or presence of allergy or intolerance to the study drugs or their components or drugs of their class. In addition, if heparin is used during pharmacokinetic sampling, participants with a history of sensitivity to heparin or heparin-induced thrombocytopenia must not be enrolled.
  • Current or anticipated need for chronic anti-coagulation with the exception of the use of low dose acetylsalicylic acid (<=325 mg) or hereditary coagulation and platelet disorders such as hemophilia or Von Willebrand Disease.
  • Any evidence of primary resistance based on the presence of any major known Integrase inhibitor (INI) or Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutation, except for K103N by any historical resistance test result.
  • Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening phase to verify a result.
  • Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the subject's participation in the study of an investigational compound.
  • Subjects has estimated creatine clearance <50mL/minute per 1.73 meter square (m^2) via Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) Method
  • Alanine aminotransferase (ALT) >=3 × Upper limit of normal (ULN)
  • Exposure to an experimental drug (with the exception of those in the ATLAS study including CAB, CAB LA, and RPV LA) or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to Day 1 of this study.
  • Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; tuberculosis therapy with the exception of isoniazid (isonicotinylhydrazid, INH); anti--coagulation agents; Immunomodulators that alter immune responses such as chronic systemic corticosteroids, interleukins, or interferons. Note: Subjects using short-term (e.g. <=21 days) systemic corticosteroid treatment; topical, inhaled and intranasal corticosteroids are eligible for enrollment.
  • Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening
  • Treatment with any agent, except recognized ART as allowed above, with documented activity against HIV-1 within 28 days of study Day 1. Treatment with acyclovir/valacyclovir is permitted.
  • Use of medications which are associated with Torsade de Pointes.
  • Current or prior history of etravirine (ETR) use.
  • Current use of tipranavir/ritonavir or fosamprenavir/ritonavir.
  • Subjects receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication.
  • Participation in other interventional studies or non-interventional studies that require any type of assessment outside the local standard of care practices is generally not permitted, however for eligible subjects in South Africa only, co-enrolment in the AIDS Clinical Trial Group ACTG interventional study (A5392) could be exceptionally permitted after review and approval by the Medical Monitor.
  • Sub-study exclusion criteria
  • More than 1 plasma HIV-1 RNA measurement =>50 c/mL to <200 c/mL (virologic blip) within 24 weeks prior to sub-study Screening visit.
  • Any Suspected Virologic Failure (HIV-RNA>200 c/mL)
  • Participants planning to require oral bridging during participation in the ATLAS-2M sub-study
  • Participant has a tattoo or any dermatological condition overlying the thigh region which may interfere with interpretation of injection site reactions
  • Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to receive study medication

Trial locations and contacts

119 sites in 13 countries.

119 sites in 13 countries

United States43 sites

  • GSK Investigational Site

    Allentown, Pennsylvania, 18102

  • GSK Investigational Site

    Annandale, Virginia, 22003

  • GSK Investigational Site

    Augusta, Georgia, 30912-3130

  • GSK Investigational Site

    Austin, Texas, 78705-3326

  • GSK Investigational Site

    Bakersfield, California, 93301

  • GSK Investigational Site

    Bellaire, Texas, 77401

  • GSK Investigational Site

    Beverly Hills, California, 90211

  • GSK Investigational Site

    Birmingham, Alabama, 35294

  • GSK Investigational Site

    Boston, Massachusetts, 02129

  • GSK Investigational Site

    Chapel Hill, North Carolina, 27599

  • GSK Investigational Site

    Charlotte, North Carolina, 28204

  • GSK Investigational Site

    Chicago, Illinois, 60611-2826

  • GSK Investigational Site

    Cincinnati, Ohio, 45267-0405

  • GSK Investigational Site

    Dallas, Texas, 75246-2004

  • GSK Investigational Site

    Denver, Colorado, 80246-1438

  • GSK Investigational Site

    Fort Lauderdale, Florida, 33316

  • GSK Investigational Site

    Fort Worth, Texas, 76104

  • GSK Investigational Site

    Ft. Pierce, Florida, 34982-7148

  • GSK Investigational Site

    Houston, Texas, 77098

  • GSK Investigational Site

    Long Beach, California, 90813

  • GSK Investigational Site

    Longview, Texas, 75605-2410

  • GSK Investigational Site

    Los Angeles, California, 90027

  • GSK Investigational Site

    Los Angeles, California, 90036

  • GSK Investigational Site

    Los Angeles, California, 90069

  • GSK Investigational Site

    Lynchburg, Virginia, 24501

  • GSK Investigational Site

    Macon, Georgia, 31201

  • GSK Investigational Site

    Minneapolis, Minnesota, 55415

  • GSK Investigational Site

    New York, New York, 10029

  • GSK Investigational Site

    New York, New York, 10065

  • GSK Investigational Site

    Omaha, Nebraska, 68198-8106

  • GSK Investigational Site

    Palm Springs, California, 92264-5220

  • GSK Investigational Site

    Phoenix, Arizona, 85015

  • GSK Investigational Site

    Pittsburgh, Pennsylvania, 15212

  • GSK Investigational Site

    San Francisco, California, 94109

  • GSK Investigational Site

    San Francisco, California, 94110

  • GSK Investigational Site

    San Francisco, California, 94118

  • GSK Investigational Site

    Sarasota, Florida, 34237-3116

  • GSK Investigational Site

    St Louis, Missouri, 63110-1035

  • GSK Investigational Site

    Torrance, California, 90502

  • GSK Investigational Site

    Vero Beach, Florida, 32690

  • GSK Investigational Site

    Washington D.C., District of Columbia, 20005

  • GSK Investigational Site

    Washington D.C., District of Columbia, 20007

  • GSK Investigational Site

    Washington D.C., District of Columbia, 20037

Other trials in United States

Spain14 sites

  • GSK Investigational Site

    Badalona, Barcelona, 08916

  • GSK Investigational Site

    Barcelona, 08003

  • GSK Investigational Site

    Barcelona, 08035

  • GSK Investigational Site

    Barcelona, 08036

  • GSK Investigational Site

    Córdoba, 14004

  • GSK Investigational Site

    Elche Alicante, 03203

  • GSK Investigational Site

    Madrid, 28034

  • GSK Investigational Site

    Madrid, 28041

  • GSK Investigational Site

    Madrid, 28046

  • GSK Investigational Site

    Málaga, 29010

  • GSK Investigational Site

    Santiago de Compostela, 15706

  • GSK Investigational Site

    Seville, 41013

  • GSK Investigational Site

    Valencia, 46014

  • GSK Investigational Site

    Vigo Pontevedra, 36312

Other trials in Spain

Russia13 sites

  • GSK Investigational Site

    Kazan', 420049

  • GSK Investigational Site

    Kemerovo, 650056

  • GSK Investigational Site

    Krasnodar, 350015

  • GSK Investigational Site

    Lipetsk, 398043

  • GSK Investigational Site

    Moscow, 115035

  • GSK Investigational Site

    Oryol, 302040

  • GSK Investigational Site

    Saint Petersburg, 190103

  • GSK Investigational Site

    Saint Petersburg, 193167

  • GSK Investigational Site

    Saint Petersburg, 196645

  • GSK Investigational Site

    Saratov, 410009

  • GSK Investigational Site

    Smolensk, 214006

  • GSK Investigational Site

    Toliyatti, 445846

  • GSK Investigational Site

    Yekaterinburg, 620102

Other trials in Russia

Germany10 sites

  • GSK Investigational Site

    Berlin, 10439

  • GSK Investigational Site

    Berlin, 10787

  • GSK Investigational Site

    Bonn, 53127

  • GSK Investigational Site

    Essen, North Rhine-Westphalia, 45122

  • GSK Investigational Site

    Frankfurt, 60590

  • GSK Investigational Site

    Frankfurt, 60596

  • GSK Investigational Site

    Hamburg, 20146

  • GSK Investigational Site

    Hamburg, 20246

  • GSK Investigational Site

    Hanover, Lower Saxony, 30625

  • GSK Investigational Site

    München, 80337

Other trials in Germany

France8 sites

  • GSK Investigational Site

    Montpellier, 34295

  • GSK Investigational Site

    Paris, 75012

  • GSK Investigational Site

    Paris, 75013

  • GSK Investigational Site

    Paris, 75018

  • GSK Investigational Site

    Paris, 75475

  • GSK Investigational Site

    Saint-Denis, 93200

  • GSK Investigational Site

    Toulouse, 31059

  • GSK Investigational Site

    Tourcoing, 59208

Other trials in France

South Africa7 sites

  • GSK Investigational Site

    Bloemfontein, 9300

  • GSK Investigational Site

    Cape Town, 7925

  • GSK Investigational Site

    Durban, 4001

  • GSK Investigational Site

    Durban, 4052

  • GSK Investigational Site

    Durban, 4091

  • GSK Investigational Site

    Johannesburg, 2113

  • GSK Investigational Site

    Middelburg, Mpumalanga, 1055

Other trials in South Africa

Canada6 sites

  • GSK Investigational Site

    Montreal, Quebec, H2L 4E9

  • GSK Investigational Site

    Montreal, Quebec, H4A 3J1

  • GSK Investigational Site

    Ottawa, Ontario, K1H 8L6

  • GSK Investigational Site

    Québec, Quebec, G1V 4G2

  • GSK Investigational Site

    Regina, Saskatchewan, S4P 0W5

  • GSK Investigational Site

    Toronto, Ontario, M5G 1K2

Other trials in Canada

South Korea5 sites

  • GSK Investigational Site

    Daegu, 41944

  • GSK Investigational Site

    Daejeon, 35015

  • GSK Investigational Site

    Pusan, 49241

  • GSK Investigational Site

    Seoul, 03722

  • GSK Investigational Site

    Seoul, 06591

Other trials in South Korea

Argentina4 sites

  • GSK Investigational Site

    Buenos Aires, 1141

  • GSK Investigational Site

    Buenos Aires, C1202ABB

  • GSK Investigational Site

    Ciudad Autonoma Buenos Aires, C1405CKC

  • GSK Investigational Site

    Rosario, S2000PBJ

Other trials in Argentina

Australia3 sites

  • GSK Investigational Site

    Darlinghurst, New South Wales, 2010

  • GSK Investigational Site

    Prahran, Prahran 3181

  • GSK Investigational Site

    Sydney, New South Wales, 2010

Other trials in Australia

Sweden3 sites

  • GSK Investigational Site

    Gothenburg, SE-416 85

  • GSK Investigational Site

    Stockholm, SE-118 83

  • GSK Investigational Site

    Stockholm, SE-14186

Other trials in Sweden

Italy2 sites

  • GSK Investigational Site

    Brescia, 25123

  • GSK Investigational Site

    Milan, 20157

Other trials in Italy

Mexico1 site

  • GSK Investigational Site

    Guadajalara, 44280

Other trials in Mexico

About this study

Official title: A Phase IIIb, Randomized, Multicenter, Parallel-group, Non-inferiority, Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Long-acting Cabotegravir Plus Long-acting Rilpivirine Administered Every 8 Weeks or Every 4 Weeks in HIV-1-infected Adults Who Are Virologically Suppressed

This Antiretroviral Therapy as Long Acting Suppression every 2 Months (ATLAS-2M) study is designed to demonstrate the non-inferior antiviral activity and safety of CAB LA + RPV LA administered every 8 weeks (Q8W) compared to CAB LA + RPV LA administered every 4 weeks (Q4W) over a 48-week treatment period in approximately 1020 adult HIV-1 infected subjects. Subjects will be divided in 2 groups; Group 1 will include subjects receiving current anti-retroviral (ART) standard of care (SOC) therapy whereas group 2 will include subjects currently receiving CAB LA + RPV LA Q4W in ATLAS study. Subjects in both groups will be randomized to receive CAB LA + RPV LA Q4W or Q8W. The study will be carried out in 3 phases including screening phase, maintenance phase and extension phase. Subjects choosing not to enter the Extension phase can complete their study participation at the Week 100 visit and enter into the 52-week Long-Term Follow-Up (LTFU) Phase as required. A sub-study in the ATLAS-2M study will evaluate the pharmacokinetics, tolerability and efficacy of CAB and RPV long acting injections following intramuscular administration in the Vastus Lateralis Muscle (thigh) in HIV-infected Adult Participants who have received at least three years of Gluteal Injections in this ATLAS-2M Study.

Conditions
HIV Infections
Being tested
Cabotegravir Tablets, Rilpivirine Tablets, Cabotegravir Injectable Suspension, Rilpivirine Injectable Suspension
Keywords
Long acting Cabotegravir, Safety, HIV-1, Efficacy, Tolerability, ATLAS-2M, Long acting Rilpivirine
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cabotegravir TabletsDrug

    CAB tablets are white to almost white oval shaped film coated 30 mg tablets for oral administration. CAB tablets are to be stored up to 30 degree Celsius and protected from moisture.

  • Rilpivirine TabletsDrug

    RPV tablets are 25 mg tablets that are off-white, round, biconvex, film-coated and debossed on one side with "TMC" and the other side with "25". RPV tablets should be stored at 25 degree Celsius (excursions permitted to 15 degree-30 degree Celsius) and protected from light.

  • Cabotegravir Injectable SuspensionDrug

    CAB LA injectable suspension is a sterile white to slightly pink suspension containing 200 mg/mL of GSK1265744 as free acid for administration by IM injection. CAB LA injectable suspension is to be stored at up to 30 degree Celsius and should not be frozen.

  • Rilpivirine Injectable SuspensionDrug

    RPV LA injectable suspension is a sterile white suspension containing 300 mg/mL of RPV as the free base for administration by IM injection. RPV LA injectable suspension should be kept in the outer package and stored at 2-8 degree Celsius and should not be frozen. RPV LA should also be protected from light.

Study groups in NCT03299049
Study groupRoleWhat they receive
Subjects in group 1 receiving study treatment once in 4 weeksExperimentalGroup 1 will consist of subjects randomized from current ART SOC therapy. Subjects in group 1 will be randomized to receive CAB LA plus RPV LA Q4W via intramuscular (IM) route. All subjects will receive oral therapy with CAB 30 mg + RPV 25 mg once daily prior to randomization.
Receives: Drug: Cabotegravir Tablets; Drug: Rilpivirine Tablets; Drug: Cabotegravir Injectable Suspension; Drug: Rilpivirine Injectable Suspension
Subjects in group 1 receiving study treatment once in 8 weeksExperimentalGroup 1 will consist of subjects randomized from current ART SOC therapy. Subjects in group 1 will be randomized to receive CAB LA plus RPV LA Q8W via IM route. All subjects will receive oral therapy with CAB 30 mg + RPV 25 mg once daily prior to randomization.
Receives: Drug: Cabotegravir Tablets; Drug: Rilpivirine Tablets; Drug: Cabotegravir Injectable Suspension; Drug: Rilpivirine Injectable Suspension
Subjects in group 2 receiving study treatment once in 4 weeksExperimentalGroup 2 will consist of subjects currently receiving CAB LA + RPV LA Q4W in ATLAS study. Subjects in Group 2 will be randomized to continue CAB LA plus RPV LA Q4W administration via IM route.
Receives: Drug: Cabotegravir Injectable Suspension; Drug: Rilpivirine Injectable Suspension
Subjects in group 2 receiving study treatment once in 8 weeksExperimentalGroup 2 will consist of subjects currently receiving CAB LA + RPV LA Q4W in ATLAS study. Subjects in Group 2 will be randomized to receive CAB LA plus RPV LA Q8W via IM route.
Receives: Drug: Cabotegravir Injectable Suspension; Drug: Rilpivirine Injectable Suspension

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Plasma Human Immunodeficiency Virus-ribonucleic Acid (HIV-RNA) >=50 Copies Per Milliliter (c/mL) as Per Food and Drug Administration (FDA) Snapshot Algorithm at Week 48

    Percentage of participants with HIV-1 RNA >=50 c/mL as per FDA snapshot algorithm at Week 48 was assessed to demonstrate the non-inferior antiviral activity of CAB LA+RPV LA Q8W compared to CAB LA + RPV LA Q4W regimen over 48 weeks in HIV-1 infected ART experienced participants. The HIV-1 RNA >=50 c/mL per Snapshot algorithm was determined by the last on-treatment HIV-1 RNA measurement within the Week 48 analysis visit window. Intent-to-treat-Exposed (ITT-E) Population comprised of all randomized participants who received at least one dose of study treatment. Participants were assessed according to their randomized treatment, regardless of the treatment they received.

    Measured: Week 48

Secondary outcomes (45)

  1. Percentage of Participants With Plasma HIV-1 RNA <50 c/mL Using FDA Snapshot Algorithm at Week 48

    Percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using FDA Snapshot algorithm was assessed to demonstrate antiviral activity of CAB LA+RPV LA Q8W compared to CAB LA+ RPV LA Q4W. The HIV-1 RNA <50 c/mL per Snapshot algorithm was determined by last on-treatment HIV-1 RNA measurement within the analysis visit window. The 95% CIs were derived using normal approximation (Wald CI)

    Measured: Week 48

  2. Percentage of Participants With Plasma HIV-1 RNA <50 c/mL Using FDA Snapshot Algorithm at Week 24

    Percentage of participants with plasma HIV-1 RNA <50 c/mL at Week 48 using FDA Snapshot algorithm was assessed to demonstrate antiviral activity of CAB LA+RPV LA Q8W compared to CAB LA+ RPV LA Q4W. The HIV-1 RNA <50 c/mL per Snapshot algorithm was determined by last on-treatment HIV-1 RNA measurement within the analysis visit window. The 95% CIs were derived using normal approximation (Wald CI)

    Measured: Week 24

  3. Percentage of Participants With Protocol Defined Confirmed Virologic Failure (CVF) Through Weeks 24 and 48

    CVF was defined as rebound as indicated by two consecutive plasma HIV-1-RNA levels >=200 c/mL after prior suppression to <200 c/mL. Cumulative percentage of participants with protocol defined CVF up to Weeks 24 and 48 has been presented.

    Measured: Weeks 24 and 48

  4. Percentage of Participants With HIV-RNA >=50 c/mL as Per FDA Snapshot Algorithm at Week 24

    Percentage of participants with plasma HIV-1 RNA >=50 c/mL at Week 24 using FDA Snapshot algorithm was assessed to demonstrate antiviral activity of CAB LA+RPV LA Q8W compared to CAB LA+ RPV LA Q4W. The HIV-1 RNA >=50 c/mL per Snapshot algorithm was determined by the last on-treatment HIV-1 RNA measurement within the analysis visit window. The 95% CIs were derived using normal approximation (Wald CI).

    Measured: Weeks 24

  5. Absolute Values for HIV-1 RNA at Week 48

    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Logarithm to base 10 (log10) values for plasma HIV-1 RNA has been presented.

    Measured: Weeks 48

  6. Change From Baseline Values for HIV-1 RNA at Week 48

    Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Logarithm to base 10 values for plasma HIV-1 RNA has been presented.

    Measured: Baseline (Day 1) and Week 48

  7. Absolute Values for Cluster of Differentiation 4 Plus (CD4+) at Week 48

    Blood samples were collected and CD4+ cell count assessment by flow cytometry was carried out to evaluate the immunologic activity of CAB LA+RPV LA Q8W compared to CAB LA+RPV LA Q8W.

    Measured: Week 48

  8. Change From Baseline Values for CD4+ at Week 48

    Blood samples were collected and CD4+ cell count assessment by flow cytometry was carried out to evaluate the immunologic activity of CAB LA+RPV LA Q8W compared to CAB LA+RPV LA Q4W. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1) and Week 48

  9. Number of Participants With Non-serious Adverse Events (Non-SAEs >=5% Incidence) and Serious Adverse Events (SAEs)-Maintenance Phase

    An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. Safety Population comprised of all randomized participants who received at least one dose of study treatment. Participants were assessed according to actual treatment received.

    Measured: Up to Week 48

  10. Number of Participants With Severity of Adverse Events-Maintenance Phase

    Severity of adverse events were defined as per The Division of Acquired Immunodeficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS adverse events Grading Table). Severity grades for adverse events were as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (Potentially life-threatening) and Grade 5 (all deaths related to an AE).

    Measured: Up to Week 48

  11. Number of Participants With Maximum Post-Baseline Chemistry Toxicities-Maintenance Phase

    Clinical chemistry toxicities were graded as per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table)Blood samples were collected for the analysis of following clinical chemistry parameters: alanine aminotransferase (ALT), albumin, alkaline phosphate (ALP), aspartate aminotranferase (AST), bilirubin, carbon dioxide (CO2), cholesterol, creatinine kinase, creatinine, glomerular filtration rate (GFR) from creatinine adjusted for bovine serum albumin (BSA), glucose, hyperglycemia, hyperkalemia, hypernatremia, hypoglycemia, hypokalemia, hyponatremia, low density lipoprotein (LDL) calculation, lipase, phosphate, potassium, sodium and triglycerides. Severity grades were: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening).

    Measured: Up to Week 48

  12. Number of Participants With Maximum Post-Baseline Hematology Toxicities-Maintenance Phase

    The hematology toxicities were graded as per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table). Blood samples were collected for the analysis of following hematology parameters: hemoglobin, leukocytes, neutrophils and platelets. Severity grades were as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Potentially life-threatening).

    Measured: Up to Week 48

  13. Percentage of Participants Who Discontinued Treatment Due to Adverse Events-Maintenance Phase

    An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Percentage of participants with adverse events leading to withdrawal has been presented.

    Measured: Up to Week 48

  14. Change From Baseline in Clinical Chemistry Parameters: ALT, ALP, AST and Creatinine Kinase Over Time

    Blood samples were collected for the analysis of clinical chemical parameters including ALT, ALP, AST and creatinine kinase. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1) and Weeks 4, 8, 16, 24, 32, 40 and 48

  15. Change From Baseline in Clinical Chemistry Parameter: Albumin Over Time

    Blood samples were collected for the analysis of clinical chemistry parameter: albumin. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1) and Weeks 4, 8, 16, 24, 32, 40 and 48

  16. Change From Baseline in Clinical Chemistry Parameters: Bilirubin and Creatinine Over Time

    Blood samples were collected for the analysis of clinical chemistry parameters: bilirubin and creatinine. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1) and Weeks 4, 8, 16, 24, 32, 40 and 48

  17. Change From Baseline in Clinical Chemistry Parameters: CO2, Chloride, Phosphate, Potassium, Sodium and Urea Over Time

    Blood samples were collected for the analysis of clinical chemistry parameters: CO2, chloride, phosphate, potassium, sodium and urea. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1) and Weeks 4, 8, 16, 24, 32, 40 and 48

  18. Change From Baseline in Clinical Chemistry Parameters: Cholesterol, Glucose, Direct High Density Lipoprotein (HDL) Cholesterol, LDL Cholesterol Calculation and Triglycerides at Week 48

    Blood samples were collected for the analysis of clinical chemistry parameters: cholesterol, glucose, direct HDL cholesterol, LDL cholesterol calculation and triglycerides. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1) and Week 48

  19. Change From Baseline in Clinical Chemistry Parameter: GFR From Creatinine Adjusted Using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Over Time

    Blood samples were collected for the analysis of clinical chemistry parameter: GFR from creatinine adjusted using CKD-EPI. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1) and Weeks 4, 8, 16, 24, 32, 40 and 48

  20. Change From Baseline in Clinical Chemistry Parameter: Lipase Over Time

    Blood samples were collected for the analysis of clinical chemistry parameter: Lipase. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1) and Weeks 4, 8, 16, 24, 32, 40 and 48

  21. Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets Over Time

    Blood samples were collected for the analysis of hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1) and Weeks 4, 8, 16, 24, 32, 40 and 48

  22. Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume (MCV) Over Time

    Blood samples were collected for the analysis of hematology parameter: erythrocyte MCV. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1) and Weeks 4, 8, 16, 24, 32, 40 and 48

  23. Change From Baseline in Hematology Parameter: Erythrocytes Over Time

    Blood samples were collected for the analysis of hematology parameter: erythrocytes. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1) and Weeks 4, 8, 16, 24, 32, 40 and 48

  24. Change From Baseline in Hematology Parameter: Hematocrit Over Time

    Blood samples were collected for the analysis of hematology parameter: hematocrit. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1) and Weeks 4, 8, 16, 24, 32, 40 and 48

  25. Change From Baseline in Hematology Parameter: Hemoglobin Over Time

    Blood samples were collected for the analysis of hematology parameter: hemoglobin. Baseline value is defined as latest pre-treatment assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.

    Measured: Baseline (Day 1) and Weeks 4, 8, 16, 24, 32, 40 and 48

  26. Number of Participants With Phenotypic Resistance- Maintenance Phase

    Phenotypic resistance (PR) was analyzed in participants who met CVF criteria. PR for following Baseline third agent drugs: Integrase inhibitors(INI): bictegravir (BIC), CAB, dolutegravir (DTG), elvitegravir (EVG), raltegravir(RAL); non-nucleoside reverse transcriptase inhibitors(NNRTI): delavirdine(DLV), efavirenz(EFV), etravirine(ETR), nevirapine(NVP), RPV; nucleoside reverse transcriptase inhibitor (NRTI): lamivudine(3TC), abacavir(ABC), emtricitabine(FTC), tenofovir(TDF), zidovudine(ZDV), stavudine(d4T), didanosine(ddI) and protease inhibitors(PI): atazanavir(ATV), darunavir(DRV), fosamprenavir(FPV), indinavir(IDV), lopinavir(LPV), nelfinavir(NFV), ritonavir(RTV), saquinavir(SQV) and tipranavir (TPV) is presented. Phenotypic susceptibility was defined based on the fold change (FC) value: resistant (FC>clinical higher cutoff or biological cutoff), partially sensitive (FC<=clinical higher cutoff and > clinical lower cutoff), sensitive(FC<=clinical lower cutoff or biological cutoff)

    Measured: Up to Week 48 analysis

  27. Number of Participants With Genotypic Resistance-Maintenance Phase

    Genotypic resistance was analyzed in participants who met confirmed virologic withdrawal criteria. Genotypic Resistance data for the following Baseline third agent drugs, INI: BIC, DTG, EVG, RAL; NNRTI: DLV, EFV, ETR, NVP, RPV; NRTI: 3TC, ABC, FTC, TDF, ZDV, d4T, ddI and PI: ATV, ATV/ritonavir (r), DRV/r, FPV/r, IDV/r, LPV/r, NFV, RTV, SQV/r and TPV/r in participants meeting CVF criteria has been presented.

    Measured: Up to Week 48 analysis

  28. Number of Participants With Their Treatment Preference as Assessed Using Preference Questionnaire at Week 48 Without (w/o) Prior Exposure to CAB+RPV-CAB 600 mg LA +RPV 900 mg LA Q8W Arm Only

    Participants were administered the preference questionnaire which had 3 questions. For treatment preference, participants were required to provide their response to Question 1, which stated "Based on your experience which HIV treatment do you prefer". The responses included 1) Injectable LA HIV treatment Q4W, 2) Injectable LA HIV Treatment Q8W (only select this answer if you received the 8-week injectable regimen of CAB LA + RPV LA during study), 3) Oral daily HIV treatment and 4) No preference. Oral daily HIV Treatment refers to the oral medication of CAB + RPV subjects received during the oral lead-in period. Number of participants without prior exposure to CAB+RPV who selected each of the responses based on their treatment preference is presented.

    Measured: Week 48

  29. Number of Participants With Their Treatment Preference as Assessed Using Preference Questionnaire at Week 48 With >=1 Weeks of Prior Exposure to CAB+RPV-CAB 600 mg LA +RPV 900 mg LA Q8W Arm Only

    Participants were administered the preference questionnaire which had 3 questions. For treatment preference, participants were required to provide their response to Question 1, which stated "Based on your experience which HIV treatment do you prefer". The responses included 1) Injectable LA HIV treatment Q4W, 2) Injectable LA HIV Treatment Q8W (only select this answer if you received the 8-week injectable regimen of CAB LA + RPV LA during study), 3) Oral daily HIV treatment and 4) No preference. Oral daily HIV Treatment refers to the oral medication of CAB + RPV subjects received during the oral lead-in period. Number of participants with >=1 weeks of prior exposure to CAB+RPV who selected each of the responses based on their treatment preference is presented.

    Measured: Week 48

  30. Number of Participants With Their Treatment Preference as Assessed Using Preference Questionnaire at Week 48-CAB 400 mg LA +RPV 600 mg LA Q4W Arm Only

    Participants were administered the preference questionnaire which had 3 questions. For treatment preference, participants were required to provide their response to Question 1, which stated "Based on your experience which HIV treatment do you prefer". The responses included 1) Injectable LA HIV treatment Q4W, 2) Injectable LA HIV Treatment Q8W (only select this answer if you received the 8-week injectable regimen of CAB LA + RPV LA during study), 3) Oral daily HIV treatment and 4) No preference. Oral daily HIV Treatment refers to the oral medication of CAB + RPV participants received during the oral lead-in period. Number of participants who selected each of the responses based on their treatment preference is presented.

    Measured: Week 48

  31. Change From Baseline in Life Satisfaction (LISAT) Using HIV/AIDs-targeted Quality of Life (HATQoL) Questionnaire in Participants With or Without Prior Exposure to CAB+RPV

    The HATQoL questionnaire was used to assess the health related QoL (HRQoL). It comprises of three dimensions:LISAT, medication worries (MEDWO) and disclosure worries (DISWO). Total imputed value score for LISAT is calculated on a 0-100 scale using the formula: LISAT 100=[100 divided by (20 minus 4)]*(LISAT minus 4). A response of 5 in LISAT score shows satisfaction all of the time and 1 as none of the time. The higher the score, the greater satisfaction to life and the less worry. The transformed dimension score for each domain was summarized and analyzed. Last Observation Carried Forward (LOCF) was used as primary method of analysis. Data for participants without/with prior exposure to CAB+RPV (0 Weeks [without exposure] and >=1 Weeks [with exposure]) has been presented. Baseline value is defined as last available recorded value up to and including the Maintenance treatment start. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

    Measured: Baseline (Day 1) and Weeks 24 and 48

  32. Change From Baseline in HIV Medication, MEDWO Using HATQoL Questionnaire in Participants With or Without Prior Exposure to CAB+RPV

    The HATQoL questionnaire was used to assess the HRQoL. It comprises of three dimensions:LISAT, MEDWO and DISWO. The total imputed value score for MEDWO is calculated on a 0-100 scale using the formula: MEDWO 100=[100 divided by (25 minus 5)]*(MEDWO minus 5). A response of 1 in MEDWO score shows medication worries all of the time and 5 as none of the time. The higher the score, the greater satisfaction to life and the less worry. The transformed dimension score for each domain was summarized and analyzed. LOCF was used as primary method of analysis. Participants without/with prior exposure to CAB+RPV (0 Weeks [without exposure] and >=1 Weeks [with exposure]) has been presented. Baseline value is defined as last available recorded value up to and including the Maintenance treatment start. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

    Measured: Baseline (Day 1) and Weeks 24 and 48

  33. Change From Baseline in DISWO Using HATQoL Questionnaire in Participants With or Without Prior Exposure to CAB+RPV

    The HATQoL questionnaire was used to assess the HRQoL. It comprises of three dimensions:LISAT, MEDWO and DISWO. The total imputed value score for DISWO is calculated on a 0-100 scale using the formula: DISWO 100=[100 divided by (25 minus 5)]*(DISWO minus 5). A response of 1 in DISWO score shows disclosure worries all of the time and 5 as none of the time. The higher the score, the greater satisfaction to life and the less worry. The transformed dimension score for each domain was summarized and analyzed. LOCF was used as primary method of analysis. Participants without/with prior exposure to CAB+RPV (0 Weeks [without exposure] and >=1 Weeks [with exposure]) has been presented. Baseline value is defined as last available recorded value up to and including the Maintenance treatment start. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

    Measured: Baseline (Day 1) and Weeks 24 and 48

  34. Change From Baseline in Total Treatment Satisfaction Score Using HIV Treatment Satisfaction Status Questionnaire (HIVTSQs) at Weeks 24 and 48

    The HIVTSQs treatment satisfaction questionnaire comprises of 1-12 questions and the total treatment satisfaction score is computed with items 1-11 and summed to produce a score with a possible range of 0 to 66. Higher scores represent greater treatment satisfaction as compared to the past few weeks. LOCF was used as primary method of analysis. Participants without/with prior exposure to CAB+RPV (0 Weeks [without exposure] and >=1 Weeks [with exposure]) has been presented. Baseline value is defined as last available recorded value up to and including the Maintenance treatment start. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

    Measured: Baseline (Day 1) and Weeks 24 and 48

  35. Change From Baseline in Individual Item Scores Using HIVTSQs at Weeks 24 and 48

    HIVTSQs is a 12 item questionnaire. The individual item scores on HIVTSQs scale are rated as 6 (very satisfied, convenient, flexible, etc.) to 0 (very dissatisfied, inconvenient, inflexible, etc.). Higher scores represent greater satisfaction with each aspect of treatment. LOCF was used as primary method of analysis. Participants without/with prior exposure to CAB+RPV (0 Weeks [without exposure] and >=1 Weeks [with exposure]) has been presented. Baseline value is defined as last available recorded value up to and including the Maintenance treatment start. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

    Measured: Baseline (Day 1) and Weeks 24 and 48

  36. Total Treatment Satisfaction Change Score Using HIV Treatment Satisfaction Change Questionnaire (HIVTSQc) at Week 48

    The HIVTSQc is a 1-12 items questionnaire. Each item is scored -3 to 3. Total treatment satisfaction change score is computed using items 1 to 11 and are summed to produce a score with a possible range of -33 to 33. Higher the score, greater the improvement in satisfaction with treatment; the lower the score, the greater the deterioration in satisfaction with treatment. A score of 0 represented no change. LOCF was used as primary method of analysis. Total treatment satisfaction change score for participants who entered the current study from Q4W arm of ATLAS (NCT number: NCT02951052) and from either standard of care (SOC) arms of ATLAS or the new SOC participants) has been presented.

    Measured: Week 48

  37. Change From Week 8 in Dimension Scores Using Perception of Injection (PIN) Questionnaire.

    The PIN questionnaire explores bother of pain at injection site and injection site reactions (ISR), anxiety before and after injection, willingness to receive an HIV injectable treatment the following visit and satisfaction with mode of treatment administration of individuals receiving injection and perceptions of individuals associated with receiving injections. This measure contains 21 items that measure pain at injection site, local site reactions, impact on functioning and willingness to pursue injectable treatment outside of a clinical trial. Scores range from 1 to 5, and questions are phrased in such a way as to ensure that 1 always equated with the most favourable perception of vaccination, and 5 most unfavourable. Dimension scores include bother from ISR, leg movement, sleep and acceptability. Score of a domain is calculated as mean of all items within the domain. Higher scores represent worse perception of injection. LOCF was used as primary method of analysis.

    Measured: Week 8 and Weeks 24 and 48

  38. Change From Week 8 in Individual Item Scores (Anxiety Before, Pain, Satisfaction, Anxiety After and Willingness) Using Perception of Injection (PIN) Questionnaire.

    The PIN questionnaire explores the bother of pain at the injection site and ISRs, anxiety before and after injection, willingness to receive an HIV injectable treatment the following visit and satisfaction with the mode of treatment administration of individuals receiving injection and perceptions of individuals associated with receiving injections. This measure contains 21 items that measure pain at injection site, local site reactions, impact on functioning and willingness to pursue injectable treatment outside of a clinical trial. The items in the scale are rated on a 5-point scale ranging from 1(very dissatisfied, extremely, etc.) to 5 (very satisfied, not at all, etc.). Lower scores represent worse perception of injection. LOCF was used as primary method of analysis.

    Measured: Week 8 and Weeks 24 and 48

  39. Change From Baseline in Treatment Acceptance a Using "General Acceptance" Dimension of the Chronic Treatment Acceptance (ACCEPT) Questionnaire in Participants With or Without Prior Exposure to CAB+RPV

    The ACCEPT questionnaire is a generic medication acceptance measure assessing how participants weigh advantages and disadvantages of long-term medication.The questionnaire consists of 25 items that capture six dimensions.3 questions that focus on general acceptance of study medication were analyzed.Items on the scale are rated as 1-5 scores:1:not at all acceptable,2:not very acceptable,3:somewhat acceptable, 4:totally acceptable and 5:I don't know.Total score of the dimension is calculated as the mean of recoded items of the dimension and then linearly transformed to be on a scale from 0 to 100:Total Score=(mean of the recoded items in the dimension minus1)divided by2*100. LOCF was used as primary method of analysis. Data for participants without or with prior exposure has been presented. Baseline value is defined as last available value up to and including the Maintenance treatment. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

    Measured: Baseline (Day 1) and Weeks 24 and 48

  40. Plasma Trough Concentration (Ctrough) for CAB LA Evaluable

    Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of CAB LA. PK Population comprises of all participants who received CAB and / or RPV and underwent PK sampling during the study and provide at least 1 non-missing CAB and / or RPV plasma concentration value (Non-quantifiable [NQ] values will be considered as non-missing values).

    Measured: Pre-dose at Weeks 4, 8, 16, 24, 32, 40 and 48

  41. Plasma Ctrough for RPV LA Evaluable

    Blood samples were collected at indicated time points for PK analysis of RPV LA.

    Measured: Pre-dose at Weeks 4, 8, 16, 24, 32, 40 and 48

  42. Area Under the Curve (AUC) for CAB LA

    Blood samples were collected at indicated time points to analyze concentration in plasma for CAB LA. Participants who transitioned from ATLAS (201585 - NCT02951052) into this ATLAS-2M (207966) study had been treated with CAB + RPV for at least one year, were approaching steady state exposures, and were therefore excluded in order to focus the population analysis on those without prior exposure.

    Measured: Predose at Weeks 4, 8, 13, 24, 32, 40, 48; 1 Week post-dose at Week 9 and 41

  43. AUC for RPV LA

    Blood samples were collected at indicated time points to analyze concentration in plasma for RPV LA. Participants who transitioned from ATLAS (201585 - NCT02951052) into this ATLAS-2M (207966) study had been treated with CAB + RPV for at least one year, were approaching steady state exposures, and were therefore excluded in order to focus the population analysis on those without prior exposure.

    Measured: Predose at Weeks 4, 8, 13, 24, 32, 40, 48; 1 Week post-dose at Week 9 and 41

  44. Maximum Concentration (Cmax) in Plasma for CAB LA Evaluable

    Blood samples were collected at indicated time points to analyze Cmax in plasma for CAB LA. Participants who transitioned from ATLAS (201585 - NCT02951052) into this ATLAS-2M (207966) study had been treated with CAB + RPV for at least one year, were approaching steady state exposures, and were therefore excluded in order to focus the population analysis on those without prior exposure.

    Measured: Predose at Weeks 4, 8, 13, 24, 32, 40, 48; 1 Week post-dose at Week 9 and 41

  45. Cmax in Plasma for RPV LA Evaluable

    Blood samples were collected at indicated time points to analyze Cmax in plasma for RPV LA. Participants who transitioned from ATLAS (201585 - NCT02951052) into this ATLAS-2M (207966) study had been treated with CAB + RPV for at least one year, were approaching steady state exposures, and were therefore excluded in order to focus the population analysis on those without prior exposure.

    Measured: Predose at Weeks 4, 8, 13, 24, 32, 40, 48; 1 Week post-dose at Week 9 and 41

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Oct 2017
  2. Study start27 Oct 2017
  3. Primary completion6 Jun 2019
  4. Study completion31 Dec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Two groups of subjects will be randomized to receive CAB LA + RPV LA Q4W, or CAB LA + RPV LA Q8W regimen
Masking
None (open label)
Enrolment
1,049 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03299049
Sponsor's protocol ID
207966
Other IDs
2017-002946-62, 2017
Acronym
ATLAS-2M
Status last verified
Sep 2026
First submitted
26 Sep 2017
Last updated
21 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: IPD for this study will be made available via the Clinical Study Data Request site.

Publications

  • Overton ET, Richmond G, Rizzardini G, Jaeger H, Orrell C, Nagimova F, Bredeek F, Garcia Deltoro M, Swindells S, Andrade-Villanueva JF, Wong A, Khuong-Josses MA, Van Solingen-Ristea R, van Eygen V, Crauwels H, Ford S, Talarico C, Benn P, Wang Y, Hudson KJ, Chounta V, Cutrell A, Patel P, Shaefer M, Margolis DA, Smith KY, Vanveggel S, Spreen W. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet. 2021 Dec 19;396(10267):1994-2005. doi: 10.1016/S0140-6736(20)32666-0. Epub 2020 Dec 9.

    PubMed 33308425

  • Overton ET, Richmond G, Rizzardini G, Thalme A, Girard PM, Wong A, Porteiro N, Swindells S, Reynes J, Noe S, Harrington C, Espanol CM, Acuipil C, Aksar A, Wang Y, Ford SL, Crauwels H, van Eygen V, Van Solingen-Ristea R, Latham CL, Thiagarajah S, D'Amico R, Smith KY, Vandermeulen K, Spreen WR. Long-Acting Cabotegravir and Rilpivirine Dosed Every 2 Months in Adults With Human Immunodeficiency Virus 1 Type 1 Infection: 152-Week Results From ATLAS-2M, a Randomized, Open-Label, Phase 3b, Noninferiority Study. Clin Infect Dis. 2023 May 3;76(9):1646-1654. doi: 10.1093/cid/ciad020.

    PubMed 36660819

  • Elliot ER, Polli JW, Patel P, Garside L, Grove R, Barnett V, Roberts J, Byrapuneni S, Crauwels H, Ford SL, Van Solingen-Ristea R, Birmingham E, D'Amico R, Baugh B, van Wyk J. Efficacy, Safety, and Pharmacokinetics by Body Mass Index Category in Phase 3/3b Long-Acting Cabotegravir Plus Rilpivirine Trials. J Infect Dis. 2024 Jul 25;230(1):e34-e42. doi: 10.1093/infdis/jiad580.

    PubMed 39052748

  • Moreno S, Rivero A, Ventayol P, Falco V, Torralba M, Schroeder M, Neches V, Vallejo-Aparicio LA, Mackenzie I, Turner M, Harrison C. Cabotegravir and Rilpivirine Long-Acting Antiretroviral Therapy Administered Every 2 Months is Cost-Effective for the Treatment of HIV-1 in Spain. Infect Dis Ther. 2023 Aug;12(8):2039-2055. doi: 10.1007/s40121-023-00840-y. Epub 2023 Jul 14.

    PubMed 37452174

  • Chounta V, Snedecor SJ, Wu S, Van de Velde N. Indirect comparison of 48-week efficacy and safety of long-acting cabotegravir and rilpivirine maintenance every 8 weeks with daily oral standard of care antiretroviral therapy in participants with virologically suppressed HIV-1-infection. BMC Infect Dis. 2022 May 4;22(1):428. doi: 10.1186/s12879-022-07243-3.

    PubMed 35508986

  • Jaeger H, Overton ET, Richmond G, Rizzardini G, Andrade-Villanueva JF, Mngqibisa R, Hermida AO, Thalme A, Belonosova E, Ajana F, Benn PD, Wang Y, Hudson KJ, Espanol CM, Ford SL, Crauwels H, Margolis DA, Talarico CL, Smith KY, van Eygen V, Van Solingen-Ristea R, Vanveggel S, Spreen WR. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 96-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet HIV. 2021 Nov;8(11):e679-e689. doi: 10.1016/S2352-3018(21)00185-5. Epub 2021 Oct 11.

    PubMed 34648734

  • Swindells S, Lutz T, Van Zyl L, Porteiro N, Stoll M, Mitha E, Shon A, Benn P, Huang JO, Harrington CM, Hove K, Ford SL, Talarico CL, Chounta V, Crauwels H, Van Solingen-Ristea R, Vanveggel S, Margolis DA, Smith KY, Vandermeulen K, Spreen WR. Week 96 extension results of a Phase 3 study evaluating long-acting cabotegravir with rilpivirine for HIV-1 treatment. AIDS. 2022 Feb 1;36(2):185-194. doi: 10.1097/QAD.0000000000003025.

    PubMed 34261093

  • Chounta V, Overton ET, Mills A, Swindells S, Benn PD, Vanveggel S, van Solingen-Ristea R, Wang Y, Hudson KJ, Shaefer MS, Margolis DA, Smith KY, Spreen WR. Patient-Reported Outcomes Through 1 Year of an HIV-1 Clinical Trial Evaluating Long-Acting Cabotegravir and Rilpivirine Administered Every 4 or 8 Weeks (ATLAS-2M). Patient. 2021 Nov;14(6):849-862. doi: 10.1007/s40271-021-00524-0. Epub 2021 May 31.

    PubMed 34056699

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cabotegravir Tablets, Rilpivirine Tablets and Cabotegravir Injectable Suspension in people with HIV Infections, run by ViiV Healthcare at 119 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 52 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 21 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 119 sites in United States, Spain, Russia, Germany, France and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Plasma Human Immunodeficiency Virus-ribonucleic Acid (HIV-RNA) >=50 Copies Per Milliliter (c/mL) as Per Food and Drug Administration (FDA) Snapshot Algorithm at Week 48 (time frame: Week 48). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03299049, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in