Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT04564547 | Dose Ranging, Switch Study of Islatravir (MK-8591) and Ulonivirine (MK-8507) Once-Weekly in Virologically-Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) [MK-8591-013] | PHASE2 | COMPLETED | 161 | — | — | Mar 9, 2021 | Jan 30, 2025 | Jan 26, 2026 | 23 | United States, France +1 |
| NCT04003103 | Safety and Pharmacokinetics of Oral Islatravir (MK-8591) Once Monthly in Participants at Low Risk of Human Immunodeficiency Virus 1 (HIV-1) Infection (MK-8591-016) | PHASE2 | COMPLETED | 242 | — | — | Sep 19, 2019 | Nov 24, 2022 | Jul 18, 2025 | 9 | United States, Israel +1 |
| NCT03272347 | Islatravir (MK-8591) With Doravirine and Lamivudine in Participants Infected With Human Immunodeficiency Virus Type 1 (MK-8591-011) | PHASE2 | COMPLETED | 123 | — | — | Nov 27, 2017 | Mar 9, 2022 | Mar 29, 2023 | 26 | United States, Chile +2 |
| NCT04568603 | Islatravir and Methadone Pharmacokinetics (MK-8591-029) | PHASE1 | COMPLETED | 14 | — | — | Oct 16, 2020 | Jul 9, 2021 | Jan 28, 2025 | 2 | United States |
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. As pre-specified in the protocol and supplemental statistical analysis plan (sSAP), presented here is the percentage of participants who experienced one or more AEs during the Double-blind Treatment Period and includes the 42 days following the final dose of double-blind study intervention.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. As pre-specified in the protocol and sSAP, presented here is the percentage of participants who discontinued double-blind study intervention due to an AE during the Double-Blind Treatment Period.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. As pre-specified in the protocol and sSAP, presented here is the percentage of participants who experienced one or more AEs during the Unblinded Safety Monitoring Period, beginning 42 days following the final dose of double-blind study intervention.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study therapy.
A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, that is considered related to the study intervention.
An 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 or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study therapy, whether or not considered related to the study intervention. Toxicity grading was according to the National Institutes of Health Division of AIDS (NIH DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events version 2.1 (Grade 3 is 'severe'; Grade 4 is 'potentially life-threatening'; and Grade 5 'results in death').
An drug-related 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 or significant disability/incapacity; is a congenital anomaly/birth defect; or is an other important medical event, that is considered related to study therapy.
A drug-related Grade 3 to Grade 5 AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention; has a toxicity Grade 3 (severe), 4 (potentially life-threatening), or 5 (results in death); and is considered related to study therapy. Toxicity grading was according to the NIH DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (v. 2.1).
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
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.
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.
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.
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 AUC0-24 of R-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.
The AUC0-24hr of S-methadone was determined on Day 1 (methadone) and Day 2 (methadone + ISL). Back-transformed least-squares mean and confidence interval from mixed effects model were performed on natural log-transformed values; data show the geometric least squares mean.
| Arm | Type | Description |
|---|---|---|
| Group 1: ISL 20 mg + Ulonivirine 100 mg | EXPERIMENTAL | Participants receive ISL 20 mg + ulonivirine 100 mg once weekly (QW) and placebo to BIC/FTC/TAF once daily (QD). Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART. |
| Group 2: ISL 20 mg + Ulonivirine 200 mg | EXPERIMENTAL | Participants receive ISL 20 mg + ulonivirine 200 mg QW and placebo to BIC/FTC/TAF QD. Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART. |
| Group 3: ISL 20 mg + Ulonivirine 400 mg | EXPERIMENTAL | Participants receive ISL 20 mg + ulonivirine 400 mg QW and placebo to BIC/FTC/TAF QD. Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART. |
| Group 4: BIC/FTC/TAF | ACTIVE_COMPARATOR | Participants receive placebo to ISL + placebo to ulonivirine QW and BIC/FTC/TAF 50 mg/200 mg/25 mg QD. |
| Islatravir 60 mg | EXPERIMENTAL | 60 mg islatravir + placebo for islatravir administered once monthly, orally in capsule form for 24 weeks |
| Islatravir 120 mg | EXPERIMENTAL | 120 mg islatravir administered once monthly, orally in capsule form for 24 weeks |
| Placebo | PLACEBO_COMPARATOR | Placebo for islatravir administered once monthly, orally in capsule form for 24 weeks |
| 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. |
| 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. |
| 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. |
| 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. |
| Methadone + ISL | EXPERIMENTAL | Methadone-maintained participants (20 to 200 mg \[locally-provided\] once daily \[QD\] from Day -14 to Day -1 and Day 10 to Day 15) receive methadone 20 to 200 mg QD on Day 1 to Day 9; ISL 60 mg is co-administered with methadone on Day 2. |
| Name | Type | Description |
|---|---|---|
| Islatravir | DRUG | ISL capsule taken by mouth. |
| Ulonivirine | DRUG | Ulonivirine tablet taken by mouth. |
| BIC/FTC/TAF | DRUG | BIC/FTC/TAF tablet taken by mouth. |
| Placebo to ISL | DRUG | Placebo capsule matched to ISL taken by mouth. |
| Placebo to Ulonivirine | DRUG | Placebo tablet matched to ulonivirine taken by mouth. |
| Placebo to BIC/FTC/TAF | DRUG | Placebo tablet matched to BIC/FTC/TAF taken by mouth. |
| Placebo | DRUG | Placebo capsules taken by mouth. |
| Placebo to Islatravir | DRUG | Placebo to islatravir is orally administered QD in capsule form for up to 52 weeks |
| Doravirine | DRUG | Doravirine 100 mg is orally administered QD in tablet form for up to 144 weeks |
| Placebo to Doravirine | DRUG | Placebo to Doravirine is orally administered QD in tablet form for up to 52 weeks |
| Lamivudine | DRUG | Lamivudine 300 mg is orally administered QD in tablet form for up to 52 weeks |
| Placebo to Lamivudine | DRUG | Placebo to Lamivudine is orally administered QD in tablet form for up to 52 weeks |
| Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate | DRUG | 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 Fumarate | DRUG | Placebo to doravirine/lamivudine/tenofovir disoproxil fumarate is orally administered QD in tablet form for up to 52 weeks |
| Doravirine/Islatravir | DRUG | Fixed dose combination of islatravir 0.75 mg/doravirine 100 mg orally administered QD in tablet form for 48 weeks |
Inclusion Criteria: * Is HIV-1 positive with plasma human immunodeficiency virus type 1 (HIV-1) RNA \<50 copies/mL at screening * Has been virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) for ≥6 months * Has a screening CD4+ T-cell count \>200 cells/mm\^3 (c...