HIV-1 Infection
Conditions
Brief summary
This is a randomized, active-controlled, double-blind clinical study designed to evaluate the antiretroviral activity, safety, and tolerability of doravirine/islatravir (DOR/ISL \[MK-8591A\]) in treatment-naïve participants with human immunodeficiency virus type 1 (HIV-1) infection. It is hypothesized that DOR/ISL is non-inferior to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) \<50 copies/mL at Week 48.
Interventions
DRUGDOR/ISL
Fixed dose combination tablet containing DOR/ISL 100 mg/0.25 mg taken by mouth.
DRUGBIC/FTC/TAF
Fixed dose combination tablet containing BIC/FTC/TAF 50 mg/200 mg/25 mg taken by mouth.
Placebo tablet matched to DOR/ISL tablet taken by mouth.
Placebo tablet matched to BIC/FTC/TAF tablet taken by mouth.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Is HIV-1 positive with plasma HIV-1 RNA ≥500 copies/mL at screening * Is naïve to antiretroviral therapy (ART) defined as having received no prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection * If female, is not a participant of childbearing potential (POCBP); or if a POCBP, is not pregnant or breastfeeding, and is willing to use an acceptable contraceptive method or abstain from heterosexual intercourse for study duration
Exclusion criteria
* Has HIV-2 infection * Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator * Has a diagnosis of an active AIDS-defining opportunistic infection within 30 days prior to screening * Has active hepatitis B infection (defined as hepatitis B surface antigen \[HBsAg\]-positive or HBV deoxyribonucleic acid \[DNA\]-positive). * Has chronic hepatitis C virus (HCV) infection (detectable HCV ribonucleic acid \[RNA\]) and lab values are consistent with cirrhosis * Has a history of malignancy ≤5 years prior to providing documented informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma * Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality, or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants experiencing ≥1 adverse event (AE) through Week 48 | Up to 48 weeks | 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. |
| Percentage of participants with human immunodeficiency virus type 1 (HIV-1) ribonucleic acid (RNA) <50 copies/mL at Week 48 | Week 48 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a polymerase chain reaction (PCR) assay with a lower limit of detection of \<50 copies/mL. |
| Percentage of participants discontinuing from study treatment due to an AE through Week 48 | Up to 48 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96 | Week 96 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of \<50 copies/mL. |
| Percentage of participants with HIV-1 RNA <200 copies/mL at Week 144 | Week 144 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of \<50 copies/mL. |
| Change from baseline in cluster of differentiation 4+ (CD4+) T-cells at Week 48 | Baseline (Day 1) and Week 48 | CD4+ T-cells are quantified with a T and B lymphocyte and natural killer cell (TBNK) panel. |
| Change from baseline in CD4+ T-cells at Week 96 | Baseline (Day 1) and Week 96 | CD4+ T-cells are quantified with a TBNK panel. |
| Change from baseline in CD4+ T-cells at Week 144 | Baseline (Day 1) and Week 144 | CD4+ T-cells are quantified with a TBNK panel. |
| Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 | Week 96 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of \<50 copies/mL. |
| Change from baseline in body weight at Week 48 | Baseline (Day 1) and Week 48 | Body weight will be collected throughout the study. |
| Change from baseline in body weight at Week 96 | Baseline (Day 1) and Week 96 | Body weight will be collected throughout the study. |
| Change from baseline in body weight at Week 144 | Baseline (Day 1) and Week 144 | Body weight will be collected throughout the study. |
| Percentage of participants experiencing ≥1 AE through Week 144 | Up to 144 weeks | 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. |
| Percentage of participants discontinuing from study treatment due to an AE through Week 144 | Up to 144 weeks | 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. |
| Incidence of viral drug resistance | Up to 96 weeks | Plasma samples will be collected for genotypic and phenotypic HIV-1 viral drug resistance testing and used to assess resistance-associated substitutions and viral susceptibility as applicable during the study. |
| Percentage of participants with HIV-1 RNA <50 copies/mL at Week 144 | Week 144 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of \<50 copies/mL. |
| Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48 | Week 48 | Plasma HIV-1 RNA quantification will be performed at the central laboratory using a PCR assay with a lower limit of detection of \<50 copies/mL. |
Countries
Argentina, Canada, Chile, Colombia, Dominican Republic, France, Germany, Guatemala, Israel, Japan, Kenya, Malaysia, Mexico, Puerto Rico, South Africa, Spain, Switzerland, Thailand, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed