HIV-1 InfectionPhase 2NCT03272347
Islatravir (MK-8591) With Doravirine and Lamivudine in Participants Infected With Human Immunodeficiency Virus Type 1 (MK-8591-011)
A Phase 2 study testing Islatravir, Doravirine and Lamivudine in people with HIV-1 Infection, run by Merck Sharp & Dohme LLC at 26 sites in 4 countries.
Trial summary
This study will evaluate the safety, tolerability, antiretroviral activity, and pharmacokinetics of 3 doses of islatravir (MK-8591) in combination with doravirine (DOR) and lamivudine (3TC) administered to antiretroviral treatment-naïve adult participants with human immunodeficiency virus type 1 (HIV-1) infection. 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?
- Islatravir, Doravirine and Lamivudine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 123 participants
- Where
- 26 sitesin 4 countries
- Study dates
- 27 Nov 2017to 9 Mar 2022
- 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
- Has HIV-1 infection
- Is naïve to anti-retroviral therapy (ART).
- Is clinically stable, with no signs or symptoms of acute infection, at the time of entry into the study
- Female is not pregnant, not breastfeeding, not a woman of childbearing potential (WOCBP); but if WOCBP agrees to follow the contraceptive guidance
- All participants, male and female, agree to use barrier methods of contraception when engaged in any sexual activity during treatment and for 6 weeks following treatment.
Who cannot join
- Is a user of recreational or illicit drugs or has had a history of drug or alcohol abuse or dependence that may interfere with trial participation
- Has significant hypersensitivity or other contraindication to any of the components of the study drugs
- Has a history of malignancy ≤5 years prior
- Female expects to donate eggs at any time during the study
- Is breastfeeding or expecting to conceive
- A WOCBP who has a positive urine pregnancy test on Day 1 before the first dose of study treatment
Show all 14Show fewer
- Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1
- Has used systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study
- Requires any of the following prohibited medications: Carbamazepine, Phenobarbital, Phenytoin, Rifabutin, Rifampin, Herbal remedies, St. John's Wort, Modafinil, Bosentan, Nafcillin, Pentostatin
- Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 30 days of signing informed consent to participate in this current trial
- Has a documented or known virologic resistance to any approved HIV-1 reverse transcriptase inhibitor, protease inhibitor, integrase inhibitor
- Has active hepatitis C virus (HCV) coinfection defined as detectable HCV RNA or HBV co-infection defined as hepatitis B surface antigen [HBsAg]-positive
- Has a current (active) diagnosis of acute hepatitis due to any cause
- Has previously been randomized in a study and received islatravir (MK-8591), DOR, Doravirine, Tenofovir, Lamivudine, or 3TC.
Trial locations and contacts
26 sites in 4 countries.
26 sites in 4 countries
United States10 sites
Saint Hope Foundation, Inc. ( Site 0116)
Bellaire, Texas, 77401
Northstar Medical Center ( Site 0102)
Chicago, Illinois, 60657
North Texas Infectious Diseases Consultants, PA ( Site 0103)
Dallas, Texas, 75246
Tarrant County Infectious Disease Associates ( Site 0112)
Fort Worth, Texas, 76104
The Crofoot Research Center, Inc. ( Site 0118)
Houston, Texas, 77098
Kansas City CARE Clinic ( Site 0106)
Kansas City, Missouri, 64111
Orlando Immunology Center (OIC) ( Site 0105)
Orlando, Florida, 32803
Pueblo Family Physicians ( Site 0119)
Phoenix, Arizona, 85015
University California / Davis ( Site 0101)
Sacramento, California, 95817
Whitman Walker Clinic ( Site 0108)
Washington D.C., District of Columbia, 20005
France8 sites
Hopital Avicenne ( Site 2302)
Bobigny
Hopital Saint-Andre ( Site 2307)
Bordeaux
CHU Hotel Dieu ( Site 2308)
Nantes
CHU de Nice Hopital Archet 1 ( Site 2303)
Nice
Hopital Bichat - Claude Bernard ( Site 2309)
Paris
Hopital Pitie Salpetriere ( Site 2305)
Paris
Hopital Saint Louis ( Site 2306)
Paris
Centre Hospitalier de Tourcoing ( Site 2301)
Tourcoing
United Kingdom5 sites
Brighton and Sussex University Hospitals NHS Trust ( Site 2105)
Brighton, East Sussex
Chelsea and Westminster Hospital ( Site 2101)
London
Royal London Hospital ( Site 2103)
London
The Royal Free London NHS Foundation Trust ( Site 2102)
London
North Manchester General Hospital ( Site 2104)
Manchester
Chile3 sites
Clinica Arauco Salud ( Site 0200)
Santiago, RM
Biomedica Research Group ( Site 0202)
Santiago
Hospital Dr. Hernan Henriquez Aravena ( Site 0203)
Temuco
About this study
Official title: A Phase 2B, Randomized, Double-Blind, Active-Comparator-Controlled, Dose-Ranging Clinical Trial to Evaluate the Safety, Tolerability, Antiretroviral Activity, and Pharmacokinetics of MK-8591 Given in Combination With Doravirine (DOR) and Lamivudine (3TC) in HIV-1-Infected Treatment-Naïve Adults
This study will evaluate the safety, tolerability, antiretroviral activity, and pharmacokinetics of 3 doses of islatravir (MK-8591) in combination with doravirine (DOR) and lamivudine (3TC) administered to antiretroviral treatment-naïve adult participants with human immunodeficiency virus type 1 (HIV-1) infection.
- Conditions
- HIV-1 Infection
- Being tested
- Islatravir, Placebo to Islatravir, Doravirine, Placebo to Doravirine, Lamivudine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IslatravirDrug
Also called MK-8591
Islatravir at 0.25 mg, 0.75 mg or 2.25 mg is orally administered QD in capsule form for up to 52 weeks. After Week 60 a selected open label dose may be administered.
Placebo to IslatravirDrug
Placebo to islatravir is orally administered QD in capsule form for up to 52 weeks
DoravirineDrug
Also called MK-1439
Doravirine 100 mg is orally administered QD in tablet form for up to 144 weeks
Placebo to DoravirineDrug
Placebo to Doravirine is orally administered QD in tablet form for up to 52 weeks
LamivudineDrug
Also called 3TC
Lamivudine 300 mg is orally administered QD in tablet form for up to 52 weeks
Placebo to LamivudineDrug
Placebo to Lamivudine is orally administered QD in tablet form for up to 52 weeks
Doravirine/Lamivudine/Tenofovir Disoproxil FumarateDrug
Also called MK-1439A
Fixed dose combination of 100 mg doravirine + 300 mg lamivudine + 300 mg tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 144 weeks.
Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil FumarateDrug
Placebo to doravirine/lamivudine/tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 52 weeks
Doravirine/IslatravirDrug
Also called MK-8591A
Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks
| Study group | Role | What they receive |
|---|---|---|
| Islatravir 0.25 mg | Experimental | Participants will be treated once daily (QD) with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to DOR/3TC/TDF may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192. Receives: Drug: Islatravir; Drug: Doravirine; Drug: Lamivudine; Drug: Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate; Drug: Doravirine/Islatravir |
| Islatravir 0.75 mg | Experimental | Participants will be treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to DOR/3TC/TDF may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and will continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192. Receives: Drug: Islatravir; Drug: Doravirine; Drug: Lamivudine; Drug: Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate; Drug: Doravirine/Islatravir |
| Islatravir 2.25 mg | Experimental | Participants will be treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to DOR/3TC/TDF may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and will continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192. Receives: Drug: Islatravir; Drug: Doravirine; Drug: Lamivudine; Drug: Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate; Drug: Doravirine/Islatravir |
| DOR/3TC/TDF | Active comparator | Participants will be treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments may be discontinued and participants will receive only DOR/3TC/TDF QD open label up to Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192. Receives: Drug: Placebo to Islatravir; Drug: Placebo to Doravirine; Drug: Placebo to Lamivudine; Drug: Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate; Drug: Doravirine/Islatravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 24
Blood samples were collected and plasma human immunodeficiency virus 1 (HIV-1) ribonucleic acid (RNA) were quantified using a real time polymerase chain reaction (PCR) assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.
Measured: Week 24
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.
Measured: Week 48
Number of Participants Experiencing Adverse Events (AEs) up to Week 144
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Measured: Up to 144 weeks
Number of Participants Discontinuing Study Drug Due to AEs up to Week 144
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Measured: Up to 144 weeks
Secondary outcomes (14)
Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL, and missing values were counted as failure. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
Measured: Up to 24 weeks after 3TC and Placebo are discontinued from the regimen (up to approximately 60 weeks after initiating treatment)
Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After 3TC and Placebo Are Discontinued From the Regimen
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL, and missing values were counted as failure. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
Measured: Up to 48 weeks
Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After Starting Open-label Doravirine/Islatravir Regimen (Part 4)
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure. The percentage of participants with HIV-1 RNA <50 copies in Part 4 are reported.
Measured: Up to Week 192
Change From Baseline in Mature T-helper (CD4+ T)-Cell Count at Week 24
Blood samples were collected and cluster of differentiation (CD4)+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
Measured: Baseline and Week 24
Change From Baseline in CD4+ T-cell Count at Week 48
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
Measured: Baseline and Week 48
Change From Baseline in CD4+ T-cell Count at Week 96
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
Measured: Baseline and Week 96
Change From Baseline in CD4+ T-cell Count at Week 144
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Day 1 value, and baseline values were carried forward for participants who discontinue due to lack of efficacy. Post-baseline data were collected after the first dose of study medication through 14 days after the last dose of study medication.
Measured: Baseline and Week 144
Change From Baseline in CD4+ T-cell Count at Week 192 (Part 4)
Blood samples were collected and CD4+ T-cell counts were performed, where baseline measurements are defined as the Week 144 value. The change from baseline in CD4+ T-cell count at Week 192 (Part 4) are reported.
Measured: Baseline and Week 192
Number of Participants Experiencing AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
Measured: Up to 24 weeks
Number of Participants Discontinuing Study Drug Due to AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. 3TC and placebo are discontinued from the regimen from Week 24 up to Week 52.
Measured: Up to 24 weeks
Number of Participants Experiencing AEs From Week 96 Through Study Duration
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Measured: Week 96 up to Week 192
Number of Participants Discontinuing Study Drug Due to AEs From Week 96 Through Study Duration
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Measured: Week 96 up to Week 192
Number of Participants Experiencing AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who experienced AEs during Part 4 are reported.
Measured: Week 144 up to Week 192
Number of Participants Discontinuing Study Drug Due to AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4)
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. The number of participants who discontinued the study drug due to AEs in Part 4 are reported.
Measured: Week 144 up to Week 192
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2017
- Study start27 Nov 2017
- Primary completion8 Mar 2021
- Study completion9 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIV-1 InfectionStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03272347
- Sponsor's protocol ID
- 8591-011
- Other IDs
- 2017-000437-32, 2017
- Status last verified
- Feb 2023
- First submitted
- 1 Sep 2017
- Last updated
- 29 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Publications
Molina JM, Yazdanpanah Y, Afani Saud A, Bettacchi C, Chahin Anania C, Klopfer SO, Grandhi A, Eves K, Hepler D, Robertson MN, Hwang C, Hanna GJ, Correll T. Brief Report: Efficacy and Safety of Oral Islatravir Once Daily in Combination With Doravirine Through 96 Weeks for Treatment-Naive Adults With HIV-1 Infection Receiving Initial Treatment With Islatravir, Doravirine, and Lamivudine. J Acquir Immune Defic Syndr. 2022 Sep 1;91(1):68-72. doi: 10.1097/QAI.0000000000002879. Epub 2021 Dec 8.
PubMed 35972855Molina JM, Yazdanpanah Y, Afani Saud A, Bettacchi C, Chahin Anania C, DeJesus E, Olsen Klopfer S, Grandhi A, Eves K, Robertson MN, Correll T, Hwang C, Hanna GJ, Sklar P. Islatravir in combination with doravirine for treatment-naive adults with HIV-1 infection receiving initial treatment with islatravir, doravirine, and lamivudine: a phase 2b, randomised, double-blind, dose-ranging trial. Lancet HIV. 2021 Jun;8(6):e324-e333. doi: 10.1016/S2352-3018(21)00021-7. Epub 2021 May 14.
PubMed 34000227
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2B, Randomized, Double-Blind, Active-Comparator-Controlled, Dose-Ranging Clinical Trial to Evaluate the Safety, Tolerability, Antiretroviral Activity, and Pharmacokinetics of MK-8591 Given in Combination With Doravirine (DOR) and Lamivudine (3TC) in HIV-1-Infected Treatment-Naïve Adults
- ClinicalTrials.gov ID
- NCT03272347
- Acronym / sponsor ID
- 8591-011
- Conditions
- HIV-1 Infection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 27 Nov 2017 (actual)
- Primary completion
- 8 Mar 2021 (actual)
- Study completion
- 9 Mar 2022 (actual)
- First posted
- 5 Sep 2017 (actual)
- Results
- Posted 27 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety, tolerability, antiretroviral activity, and pharmacokinetics of 3 doses of islatravir (MK-8591) in combination with doravirine (DOR) and lamivudine (3TC) administered to antiretroviral treatment-naïve adult participants with human immunodeficiency virus type 1 (HIV-1) infection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Islatravir 0.25 mg | Experimental | Drug: Islatravir, Drug: Doravirine, Drug: Lamivudine, Drug: Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate, Drug: Doravirine/IslatravirParticipants will be treated once daily (QD) with 0.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to DOR/3TC/TDF may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192. |
| Islatravir 0.75 mg | Experimental | Drug: Islatravir, Drug: Doravirine, Drug: Lamivudine, Drug: Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate, Drug: Doravirine/IslatravirParticipants will be treated QD with 0.75 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to DOR/3TC/TDF may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and will continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192. |
| Islatravir 2.25 mg | Experimental | Drug: Islatravir, Drug: Doravirine, Drug: Lamivudine, Drug: Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate, Drug: Doravirine/IslatravirParticipants will be treated QD with 2.25 mg islatravir, 100 mg DOR, 300 mg 3TC, and placebo to DOR/3TC/TDF for a minimum of 24 weeks. Between week 24 through week 52, 3TC and placebo to DOR/3TC/TDF may be discontinued. Around Week 60, participants may be switched to a selected open label dose of islatravir and DOR 100 mg QD and will continue treatment until Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192. |
| DOR/3TC/TDF | Active comparator | Drug: Placebo to Islatravir, Drug: Placebo to Doravirine, Drug: Placebo to Lamivudine, Drug: Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate, Drug: Doravirine/IslatravirParticipants will be treated QD with placebo to islatravir, placebo to DOR, placebo to 3TC, and a fixed dose combination of DOR/3TC/TDF consisting of 100 mg DOR + 300 mg 3TC + 300 mg TDF for a minimum of 24 weeks. Between week 24 through week 52 placebo treatments may be discontinued and participants will receive only DOR/3TC/TDF QD open label up to Week 144. At Week 144 participants will receive the fixed dose combination of doravirine (100mg)/islatravir (0.75mg) QD open label and will continue treatment until Week 192. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Has HIV-1 infection
- Is naïve to anti-retroviral therapy (ART).
- Is clinically stable, with no signs or symptoms of acute infection, at the time of entry into the study
- Female is not pregnant, not breastfeeding, not a woman of childbearing potential (WOCBP); but if WOCBP agrees to follow the contraceptive guidance
- All participants, male and female, agree to use barrier methods of contraception when engaged in any sexual activity during treatment and for 6 weeks following treatment.
Key exclusion criteria (14 listed)
- Is a user of recreational or illicit drugs or has had a history of drug or alcohol abuse or dependence that may interfere with trial participation
- Has significant hypersensitivity or other contraindication to any of the components of the study drugs
- Has a history of malignancy ≤5 years prior
- Female expects to donate eggs at any time during the study
- Is breastfeeding or expecting to conceive
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IslatravirAlso: MK-8591Islatravir at 0.25 mg, 0.75 mg or 2.25 mg is orally administered QD in capsule form for up to 52 weeks. After Week 60 a selected open label dose may be administered. | Drug | Islatravir 0.25 mg, Islatravir 0.75 mg, Islatravir 2.25 mg |
| Placebo to IslatravirPlacebo to islatravir is orally administered QD in capsule form for up to 52 weeks | Drug | DOR/3TC/TDF |
| DoravirineAlso: MK-1439Doravirine 100 mg is orally administered QD in tablet form for up to 144 weeks | Drug | Islatravir 0.25 mg, Islatravir 0.75 mg, Islatravir 2.25 mg |
| Placebo to DoravirinePlacebo to Doravirine is orally administered QD in tablet form for up to 52 weeks | Drug | DOR/3TC/TDF |
| LamivudineAlso: 3TCLamivudine 300 mg is orally administered QD in tablet form for up to 52 weeks | Drug | Islatravir 0.25 mg, Islatravir 0.75 mg, Islatravir 2.25 mg |
| Placebo to LamivudinePlacebo to Lamivudine is orally administered QD in tablet form for up to 52 weeks | Drug | DOR/3TC/TDF |
| Doravirine/Lamivudine/Tenofovir Disoproxil FumarateAlso: MK-1439AFixed dose combination of 100 mg doravirine + 300 mg lamivudine + 300 mg tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 144 weeks. | Drug | DOR/3TC/TDF |
| Placebo to Doravirine/Lamivudine/Tenofovir Disoproxil FumaratePlacebo to doravirine/lamivudine/tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 52 weeks | Drug | Islatravir 0.25 mg, Islatravir 0.75 mg, Islatravir 2.25 mg |
| Doravirine/IslatravirAlso: MK-8591AFixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks | Drug | DOR/3TC/TDF, Islatravir 0.25 mg, Islatravir 0.75 mg, Islatravir 2.25 mg |
Primary outcome
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 24
Time frame: Week 24
Blood samples were collected and plasma human immunodeficiency virus 1 (HIV-1) ribonucleic acid (RNA) were quantified using a real time polymerase chain reaction (PCR) assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.
Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48
Time frame: Week 48
Blood samples were collected and plasma HIV-1 RNA were quantified using a real time PCR assay with a lower limit of detection of 40 copies/mL. Missing values were counted as failure.
Number of Participants Experiencing Adverse Events (AEs) up to Week 144
Time frame: Up to 144 weeks
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Number of Participants Discontinuing Study Drug Due to AEs up to Week 144
Time frame: Up to 144 weeks
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
14 secondary outcomes
Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
Time frame: Up to 24 weeks after 3TC and Placebo are discontinued from the regimen (up to approximately 60 weeks after initiating treatment)
Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After 3TC and Placebo Are Discontinued From the Regimen
Time frame: Up to 48 weeks
Percentage of Participants With HIV-1 RNA <50 Copies/mL up to 48 Weeks After Starting Open-label Doravirine/Islatravir Regimen (Part 4)
Time frame: Up to Week 192
Change From Baseline in Mature T-helper (CD4+ T)-Cell Count at Week 24
Time frame: Baseline and Week 24
Change From Baseline in CD4+ T-cell Count at Week 48
Time frame: Baseline and Week 48
Change From Baseline in CD4+ T-cell Count at Week 96
Time frame: Baseline and Week 96
Change From Baseline in CD4+ T-cell Count at Week 144
Time frame: Baseline and Week 144
Change From Baseline in CD4+ T-cell Count at Week 192 (Part 4)
Time frame: Baseline and Week 192
Number of Participants Experiencing AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
Time frame: Up to 24 weeks
Number of Participants Discontinuing Study Drug Due to AEs Through 24 Weeks After 3TC and Placebo Are Discontinued From the Regimen
Time frame: Up to 24 weeks
Number of Participants Experiencing AEs From Week 96 Through Study Duration
Time frame: Week 96 up to Week 192
Number of Participants Discontinuing Study Drug Due to AEs From Week 96 Through Study Duration
Time frame: Week 96 up to Week 192
Number of Participants Experiencing AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4)
Time frame: Week 144 up to Week 192
Number of Participants Discontinuing Study Drug Due to AEs During Open Label Doravirine/Islatravir Treatment After Week 144 up to Week 192 (Part 4)
Time frame: Week 144 up to Week 192
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35972855Molina JM, Yazdanpanah Y, Afani Saud A, Bettacchi C, Chahin Anania C, Klopfer SO, Grandhi A, Eves K, Hepler D, Robertson MN, Hwang C, Hanna GJ, Correll T. Brief Report: Efficacy and Safety of Oral Islatravir Once Daily in Combination With Doravirine Through 96 Weeks for Treatment-Naive Adults With HIV-1 Infection Receiving Initial Treatment With Islatravir, Doravirine, and Lamivudine. J Acquir Immune Defic Syndr. 2022 Sep 1;91(1):68-72. doi: 10.1097/QAI.0000000000002879. Epub 2021 Dec 8.
- Derived from this study: PubMed 34000227Molina JM, Yazdanpanah Y, Afani Saud A, Bettacchi C, Chahin Anania C, DeJesus E, Olsen Klopfer S, Grandhi A, Eves K, Robertson MN, Correll T, Hwang C, Hanna GJ, Sklar P. Islatravir in combination with doravirine for treatment-naive adults with HIV-1 infection receiving initial treatment with islatravir, doravirine, and lamivudine: a phase 2b, randomised, double-blind, dose-ranging trial. Lancet HIV. 2021 Jun;8(6):e324-e333. doi: 10.1016/S2352-3018(21)00021-7. Epub 2021 May 14.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
26 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Islatravir, Doravirine and Lamivudine in people with HIV-1 Infection, run by Merck Sharp & Dohme LLC at 26 sites in 4 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 5 inclusion and 14 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 29 Mar 2023. 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, France, United Kingdom, Chile. 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 27 Apr 2022). 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 HIV-1 RNA <50 Copies/mL at Week 24 (time frame: Week 24). The study lists 4 primary outcomes in all. 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 NCT03272347, 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 29 Mar 2023.