Proof of Concept Treatment Study of Orally Administered VH4004280 or VH4011499 in HIV-1 Infected Adults

Study Overview
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Brief Summary
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The primary purpose of the study is to evaluate the antiviral activity of orally administered VH4004280 and VH4011499 monotherapy over 10 days in human immunodeficiency virus (HIV-1) infected Treatment-Naïve (TN) participants.

Official Title
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A Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled, Phase 2a Trial to Investigate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of Orally Administered Investigational Capsid Inhibitor Monotherapy in HIV-1 Infected Treatment-Naïve Adults

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: VH4004280
* Drug: VH4011499
* Drug: VH4004280 Matching Placebo
* Drug: VH4011499 Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who are overtly healthy (other than HIV-1 infection). Screening cluster of differentiation-4 (CD4+) T-cell count greater than or equal to (≥)200 cells/microliter (µL). Documented HIV-1 infection and Screening plasma HIV-1 RNA ≥3000 copies/milliliter (mL). Treatment-naïve: Defined as no antiretroviral therapy received after the diagnosis of HIV-1 infection. Prior use of oral pre-exposure prophylaxis (PreP) is permitted. Prior use of parenteral PreP is exclusionary. Has body mass index (BMI) within the range of 18.5-31.0 kilograms per meter square (kg/m^2). Participants male at birth must use male condoms and participants female at birth who are of childbearing potential must be using acceptable forms of birth control. Participants capable of giving signed informed consent. Participant must be willing and able to start locally accessible and commercially available combination antiretroviral therapy after the monotherapy period. Exclusion Criteria: Women who are breastfeeding or plan to become pregnant or breast feed during the study. Participants with acute HIV infection. Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease. Untreated syphilis infection. Ongoing malignancy other than certain localised malignancies. Treatment with immunomodulating agents or any agent with known anti-HIV activity. Has exclusionary psychiatric, hepatic, cardiovascular gastrointestinal, renal condition. Participant having 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 take oral medication. Participants having exclusionary electrocardiogram (ECG) findings. Participants who have been exposed to any prohibited medication or vaccine. Participant positive for hepatitis B or hepatitis C. Participants with exclusionary safety laboratory (e.g Grade 3 or greater abnormality). Participants who have positive results for illicit drug use, regular use of drugs of abuse and/or excessive alcohol use.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1a - Participants Receiving VH4004280 Dose 1<br> | Drug: VH4004280<br>* VH4004280 will be administered.<br>|
| Experimental: Part 1a - Participants Receiving VH4004280 Dose 2<br> | Drug: VH4004280<br>* VH4004280 will be administered.<br>|
| Placebo Comparator: Part 1a - Participants Receiving VH4004280 Matching Placebo<br> | Drug: VH4004280 Matching Placebo<br>* VH4004280 matching placebo will be administered.<br>|
| Experimental: Part 1b - Participants Receiving VH4011499 Dose 1<br> | Drug: VH4011499<br>* VH4011499 will be administered.<br>|
| Experimental: Part 1b - Participants Receiving VH4011499 Dose 2<br> | Drug: VH4011499<br>* VH4011499 will be administered.<br>|
| Placebo Comparator: Part 1b - Participants Receiving VH4011499 Matching Placebo<br> | Drug: VH4011499 Matching Placebo<br>* VH4011499 matching placebo will be administered.<br>|
| Experimental: Part 2a - Participants Receiving VH4004280 Dose 3<br> | Drug: VH4004280<br>* VH4004280 will be administered.<br>|
| Placebo Comparator: Part 2a - Participants Receiving VH4004280 Matching Placebo<br> | Drug: VH4004280 Matching Placebo<br>* VH4004280 matching placebo will be administered.<br>|
| Experimental: Part 2b - Participants Receiving VH4011499 Dose 3<br> | Drug: VH4011499<br>* VH4011499 will be administered.<br>|
| Placebo Comparator: Part 2b - Participants Receiving VH4011499 Matching Placebo<br> | Drug: VH4011499 Matching Placebo<br>* VH4011499 matching placebo will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Change from Baseline (Day 1) in Plasma HIV-1 Ribonucleic Acid (RNA) |  | Baseline (Day 1) and up to Day 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AE) as per Severity and AEs Leading to Study Treatment Discontinuation |  | Up to Day 39 | 
| Change from Baseline for Liver Panel Laboratory Parameters: Total Bilirubin and Direct Bilirubin (Micromoles per Liter [umol/L]) |  | Baseline (Day 1) and up to Day 39 | 
| Change from Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT) Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) (International Units per Liter) |  | Baseline (Day 1) and up to Day 39 | 
| Change in Maximum Toxicity Grade from Baseline for Liver Panel Laboratory Parameters: Total Bilirubin and Direct Bilirubin (umol/L) |  | Baseline (Day 1) and up to Day 39 | 
| Change in Maximum Toxicity Grade from Baseline for Liver Panel Laboratory Parameters: ALT, ALP, and AST (International Units per Liter) |  | Baseline (Day 1) and up to Day 39 | 
| Maximum Observed Plasma Drug Concentration (Cmax) for VH4004280 |  | Up to Day 39 | 
| Maximum Observed Plasma Drug Concentration (Cmax) for VH4011499 |  | Up to Day 39 | 
| Time to Maximum Observed Plasma Drug Concentration (tmax) for VH4004280 (Hours) |  | Up to Day 39 | 
| Time to Maximum Observed Plasma Drug Concentration (tmax) for VH4011499 (Hours) |  | Up to Day 39 | 
| Plasma Concentrations of VH4004280 |  | At Day 11 | 
| Plasma Concentrations of VH4011499 |  | At Day 11 | 
| Change from baseline in plasma HIV-1 RNA relative to concentration on Day 11 (C11) for VH4004280 (copies per milliliter) | Plasma samples will be collected for quantitative analysis of HIV-1 RNA. | Baseline (Day 1) and up to Day 11 | 
| Change from baseline in plasma HIV-1 RNA relative to concentration on Day 11 (C11) for VH4011499 (copies per milliliter) | Plasma samples will be collected for quantitative analysis of HIV-1 RNA | Baseline (Day 1) and up to Day 11 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, VH4004280, VH4011499, Treatment Naïve, Phase 2a, Monotherapy