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HIV-1 InfectionPhase 2NCT02582684

Dolutegravir Plus Lamivudine Dual Therapy in Treatment Naïve HIV-1 Patients

A Phase 2 study testing Dolutegravir and Lamivudine in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 26 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study was done to see if the combination of two anti-HIV medicines, dolutegravir (DTG, Tivicay) and lamivudine (3TC, Epivir) taken once a day, provide a safe, effective, and well-tolerated treatment for HIV. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV-1 Infection
What is being tested?
Dolutegravir and Lamivudine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
122 participants
Where
26 sitesin 2 countries
Study dates
8 Dec 2015to 26 Sep 2017
Phase
Phase 2
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

  • HIV-1 infection.
  • Plasma HIV-1 RNA ≥1000 copies/mL and <500,000 copies/mL obtained within 90 days prior to study entry.
  • No evidence of any RT, any integrase, or major protease resistance mutation (according to the 2014 IAS-USA drug resistance mutations list, available at https://www.iasusa.org/sites/default/files/tam/22-3-642.pdf) based on pre-ARV (antiretroviral) treatment genotype performed any time prior to study entry.
  • ARV treatment drug-naive (defined as no previous ARV treatment at any time prior to study entry, with the exception of successful post-exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP).
  • The following laboratory values obtained within 45 days prior to study entry:
  • ANC (absolute neutrophil count) ≥750/mm^3
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  • Hemoglobin ≥10.0 g/dL
  • Platelets ≥ 50,000/mm^3
  • Calculated creatinine clearance (CrCl) ≥50 mL/min, as estimated by the Cockcroft-Gault equation
  • AST (aspartate aminotransferase) <5 x ULN (upper limit of normal)
  • ALT (alanine aminotransferase) <5x ULN
  • Total bilirubin <1.5 x ULN
  • Hepatitis B surface antigen negative within 45 days prior to study entry.
  • For women with reproductive potential, negative serum or urine pregnancy test at screening and within 48 hours prior to study entry.
  • If participating in sexual activity that could lead to pregnancy, female participants with reproductive potential must have agreed to use one form of contraceptive as listed in the protocol while receiving protocol-specified medications and for 30 days after stopping the medications.
  • Ability and willingness of participant or legal representative to provide informed consent.

Who cannot join

  • Serious illness requiring systemic treatment and/or hospitalization.
  • Treatment within 30 days prior to study entry with immune modulators such as systemic steroids, interleukins, interferons, granulocyte colony-stimulating factor (G-CSF), erythropoietin, or any investigational therapy.
  • Pregnancy or breastfeeding.
  • Receipt of systemic cytotoxic chemotherapy or dofetilide.
  • Known allergy/sensitivity to any of the study drugs or their formulations.
  • Active drug or alcohol use or dependence that may interfere with adherence to study requirements, in the opinion of the site investigator.
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  • Active hepatitis C virus (HCV) treatment or anticipated need for treatment within study period.
  • Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • Severe hepatic impairment (Class C) as determined by Child-Pugh classification.

Trial locations and contacts

26 sites in 2 countries.

26 sites in 2 countries

United States25 sites

  • The Ponce de Leon Center CRS (5802)

    Atlanta, Georgia, 30308

  • University of Colorado Hospital CRS (6101)

    Aurora, Colorado, 80045

  • Massachusetts General Hospital ACTG CRS (101)

    Boston, Massachusetts, 02114

  • Brigham and Women's Hosp. ACTG CRS (107)

    Boston, Massachusetts, 02115

  • 3201 Chapel Hill CRS

    Chapel Hill, North Carolina, 27516

  • Northwestern University CRS (2701)

    Chicago, Illinois, 60611

  • Rush Univ. Med. Ctr. ACTG CRS (2702)

    Chicago, Illinois, 60612

  • Univ. of Cincinnati CRS (2401)

    Cincinnati, Ohio, 45267

  • The Ohio State Univ. AIDS CRS (2301)

    Columbus, Ohio, 43210

  • 31443 Trinity Health and Wellness Center CRS

    Dallas, Texas, 75208

  • Greensboro CRS (3203)

    Greensboro, North Carolina, 27401

  • Houston AIDS Research Team CRS (31473)

    Houston, Texas, 77030

  • University of Southern California CRS (1201)

    Los Angeles, California, 90033

  • UCLA CARE Center CRS (601)

    Los Angeles, California, 90095

  • Univ. of Miami AIDS CRS (901)

    Miami, Florida, 33136

  • Vanderbilt Therapeutics CRS (3652)

    Nashville, Tennessee, 37204

  • Cornell CRS (7804)

    New York, New York, 10011

  • Weill Med. College of Cornell Univ., The Cornell CTU -Chelsea (7803)

    New York, New York, 10011

  • Columbia Physicians and Surgeons CRS (30329)

    New York, New York, 10032

  • Hosp. of the Univ. of Pennsylvania CRS (6201)

    Philadelphia, Pennsylvania, 19104

  • The Miriam Hospital ACTG CRS (2951)

    Providence, Rhode Island, 02906

  • University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)

    Rochester, New York, 14642

  • Ucsd, Avrc Crs (701)

    San Diego, California, 92103

  • Washington University CRS (2101)

    St Louis, Missouri, 63110

  • Harbor-UCLA Med. Ctr. CRS (603)

    Torrance, California, 90502

Other trials in United States

Puerto Rico1 site

  • Puerto Rico-AIDS CRS (5401)

    San Juan, 00935

Other trials in Puerto Rico

About this study

Official title: A Study to Evaluate Dolutegravir Plus Lamivudine Dual Therapy for the Treatment of Naïve HIV-1-infected Participants

This study was done to see if the combination of two anti-HIV medicines, dolutegravir (DTG, Tivicay) and lamivudine (3TC, Epivir) taken once a day, provide a safe, effective, and well-tolerated treatment for HIV. DTG is a type of HIV medicine called an integrase inhibitor; 3TC is a type of HIV medicine called a reverse transcriptase inhibitor. DTG works by blocking integrase and 3TC works by blocking reverse transcriptase, two HIV proteins (enzymes). This prevents HIV from multiplying and lowers the viral load (amount of HIV in the blood). Both DTG and 3TC are currently part of Food and Drug Administration (FDA) recommended regimens along with a third active drug. Since some HIV medicines have side effects and are costly, there is interest in whether HIV can be successfully controlled with fewer than three HIV drugs.

Read the detailed description

This study was a phase II, single-arm, open-label pilot study designed to estimate the efficacy of dolutegravir (DTG) plus lamivudine (3TC) as initial combination ART (antiretroviral therapy) in HIV-1 infected treatment naive participants. The target enrollment was 120 participants with a cap of N=90 participants with screening HIV-1 RNA <= 100,000 copies/mL. The study aimed to enroll >= 20% women. The expected follow-up for each participant was 52 weeks.

Visits occurred at screening, entry, and weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 from study entry. All signs/symptoms within 30 days prior to entry were recorded. Subsequently, grade 2 or higher rash and all other grade 3 or higher signs and symptoms were recorded. All participants underwent routine monitoring including plasma HIV-1 RNA levels, CD4+ cell count, hematology, chemistry, urinalysis, and pregnancy testing (for women of reproductive potential).

Population-based protease (PR), reverse transcriptase (RT) and integrase genotyping were done at the time of confirmed virologic failure. Plasma samples were stored for potential future studies to assess the impact of adherence, drug-resistant minority viral variants, and DTG exposure on virologic and CD4+ cell count responses to DTG plus 3TC. All participants also underwent UGT1A1 genotyping.

Conditions
HIV-1 Infection
Being tested
Dolutegravir, Lamivudine

What participants receive

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

  • DolutegravirDrug

    Also called DTG

    Participants were prescribed 50 mg of DTG orally daily

  • LamivudineDrug

    Also called 3TC

    Participants were prescribed 300 mg of 3TC orally daily.

Study groups in NCT02582684
Study groupRoleWhat they receive
Arm 1: DTG 50 mg + 3TC 300 mgExperimentalDolutegravir 50mg and Lamivudine 300mg, orally daily
Receives: Drug: Dolutegravir; Drug: Lamivudine

What is being measured

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

  1. Virologic Status at Week 24

    Numbers of Participants With Virologic Success, Virologic Non-Success, and no Virologic Data at Week 24 Window are provided below.

    Virologic success is defined as HIV-1 RNA <50 copies/mL and on study treatment (FDA Snapshot definition).

    Measured: At 24 weeks after study entry

Secondary outcomes (15)

  1. Virologic Status at Week 12

    Numbers of Participants With Virologic Success, Virologic Non-Success, and no Virologic Data at Week 12 Window are provided below.

    Virologic success is defined as HIV-1 RNA <50 copies/mL and on study treatment (FDA Snapshot definition).

    Measured: At 12 weeks after study entry

  2. Virologic Status at Week 48

    Numbers of Participants With Virologic Success, Virologic Non-Success, and no Virologic Data at Week 48 Window are provided below.

    Virologic success is defined as HIV-1 RNA <50 copies/mL and on study treatment (FDA Snapshot definition).

    Measured: At 48 weeks after study entry

  3. Virologic Failure

    Virologic failure is defined as follows:

    • Weeks 16 or 20: confirmed plasma HIV-1 RNA > 400 copies/mL
    • Week 24 or later: confirmed plasma HIV-1 RNA > 200 copies/mL
    1. Participants were evaluated for virologic failure regardless of whether on study treatment.
    2. Confirmation was determined based on any two consecutive evaluations meeting the virologic failure definition regardless of the time between them.
    3. Participants discontinuing the study (for any reason, including death and lost to follow-up) were considered virologic failures if their last measurement met the definition of virologic failure but no confirmatory measurement was obtained. All other participants' follow-up was censored immediately after the last available plasma HIV-1 RNA measurement.

    Measured: Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

  4. Proportion of Participants With Plasma HIV-1 RNA < 50 Copies/mL - Missing = Failure

    Proportion of participants with HIV-1 RNA < 50 copies/mL by week, ITT (Intention To Treat; missing/off study/off treatment = failure) population.

    Measured: Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

  5. Proportion of Participants With Plasma HIV-1 RNA < 200 Copies/mL - Missing = Failure

    Proportion of participants with HIV-1 RNA < 200 copies/mL by week, ITT (missing/off study/off treatment = failure) population.

    Measured: Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

  6. Proportion of Participants With Plasma HIV-1 RNA <50 Copies/mL - Missing = Ignored

    Proportion of participants with HIV-1 RNA < 50 copies/mL by week, ITT (missing = ignored) population.

    Measured: Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

  7. Proportion of Participants With Plasma HIV-1 RNA <200 Copies/mL- ITT Missing = Ignored

    Proportion of participants with HIV-1 RNA < 200 copies/mL by week, ITT (missing = ignored) population.

    Measured: Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

  8. Proportion of Participants With Plasma HIV-1 RNA <50 Copies/mL- As Treated

    Proportion of participants with HIV-1 RNA < 50 copies/mL by week, as treated population.

    Measured: Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

  9. Proportion of Participants With Plasma HIV-1 RNA <200 Copies/mL- As Treated

    Proportion of participants with HIV-1 RNA < 200 copies/mL by week, as treated population.

    Measured: Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

  10. CD4+ Cell Count

    CD4+ cell counts by study week.

    Measured: Baseline, weeks 4, 12, 24, and 48

  11. Change in CD4+ Cell Count

    Change in CD4+ cell counts by study week. Change was calculated as value at the later visit minus the value at baseline.

    Measured: Baseline, weeks 4, 12, 24, and 48

  12. Number of HIV-1 Drug Resistance Mutation Occurrences in Participants

    Number of HIV-1 drug resistance mutation occurrences participants with virologic failure and FDA snapshot non-successes. Participants that had one drug class resistance mutation may have one or more mutations.

    Measured: at the time of virologic failure

  13. Fasting Lipids and Glucose

    Fasting lipids include: total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, and glucose. Fasting was set to be 8 hours prior to the sample collection.

    Measured: Baseline and week 48

  14. Creatinine Clearance

    Creatinine clearance was estimated by the Cockcroft-Gault equation.

    Measured: Baseline, weeks 4, 12, 24, 32, 40 and 48

  15. Number of Participants With Grade 3 of Higher Adverse Events

    Number of participants who experienced an AE (sign/symptom or laboratory abnormality) of Grade 3 or higher. The AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see reference in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening.

    Measured: from study treatment dispensation through up to week 52 or until study discontinuation

Timeline

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

  1. First posted21 Oct 2015 (estimated)
  2. Study start8 Dec 2015
  3. Primary completion28 Feb 2017
  4. Study completion26 Sep 2017

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
122 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02582684
Sponsor's protocol ID
ACTG A5353
Other IDs
2UM1AI068636
Status last verified
Apr 2018
First submitted
20 Oct 2015
Last updated
9 May 2018
Data monitoring committee
Yes

Publications

  • Nyaku AN, Zheng L, Gulick RM, Olefsky M, Berzins B, Wallis CL, Godfrey C, Sax PE, Acosta EP, Haas DW, Smith KY, Sha BE, Van Dam CN, Taiwo BO; ACTG A5353 Study Team. Dolutegravir plus lamivudine for initial treatment of HIV-1-infected participants with HIV-1 RNA <500 000 copies/mL: week 48 outcomes from ACTG 5353. J Antimicrob Chemother. 2019 May 1;74(5):1376-1380. doi: 10.1093/jac/dky564.

    PubMed 30668695

  • Taiwo BO, Zheng L, Stefanescu A, Nyaku A, Bezins B, Wallis CL, Godfrey C, Sax PE, Acosta E, Haas D, Smith KY, Sha B, Van Dam C, Gulick RM. ACTG A5353: A Pilot Study of Dolutegravir Plus Lamivudine for Initial Treatment of Human Immunodeficiency Virus-1 (HIV-1)-infected Participants With HIV-1 RNA <500000 Copies/mL. Clin Infect Dis. 2018 May 17;66(11):1689-1697. doi: 10.1093/cid/cix1083.

    PubMed 29253097

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dolutegravir and Lamivudine in people with HIV-1 Infection, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 26 sites in 2 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 16 inclusion and 9 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: finished, as of the sponsor's last update on 9 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, Puerto Rico. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 30 Mar 2018). 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?

Virologic Status at Week 24 (time frame: At 24 weeks after study entry). 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 NCT02582684, which also lists 2 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 9 May 2018.

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