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

Phase 2

Completed

Conditions: HIV Infections

Interventions: Drug: VH4004280
Drug: VH4004280 Matching Placebo
Drug: VH4011499
Drug: Antiretroviral therapy
Drug: VH4011499 Matching Placebo

Registration Number: NCT06039579

Lead Sponsor: ViiV Healthcare

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 43

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 1a: VH4004280 Dose Level 1	VH4004280	Participants received a single dose of VH4004280 Dose Level 1 (low concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label antiretroviral therapy (ART) up to day 39.
Part 1a: VH4004280 Dose Level 1	Antiretroviral therapy	Participants received a single dose of VH4004280 Dose Level 1 (low concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label antiretroviral therapy (ART) up to day 39.
Part 1a: VH4004280 Dose Level 2	VH4004280	Participants received a single dose of VH4004280 Dose Level 2 (medium concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
Part 2a: VH4004280 pre-specified dose	VH4004280	Participants received a single pre-specified dose of VH4004280 (high concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
Part 1a: VH4004280 Dose Level 2	Antiretroviral therapy	Participants received a single dose of VH4004280 Dose Level 2 (medium concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
Part 2a: VH4004280 pre-specified dose	Antiretroviral therapy	Participants received a single pre-specified dose of VH4004280 (high concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
Matching placebo for VH4004280	VH4004280 Matching Placebo	Participants received a matching placebo for VH4004280 on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
Matching placebo for VH4004280	Antiretroviral therapy	Participants received a matching placebo for VH4004280 on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
Part 1b: VH4011499 Dose Level 1	VH4011499	Participants received a single dose of VH4011499 Dose Level 1 (low concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants had the option to switch to an open-label ART up to day 39.
Part 1b: VH4011499 Dose Level 1	Antiretroviral therapy	Participants received a single dose of VH4011499 Dose Level 1 (low concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants had the option to switch to an open-label ART up to day 39.
Part 1b: VH4011499 Dose Level 2	VH4011499	Participants received a single dose of VH4011499 Dose Level 2 (medium concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
Part 1b: VH4011499 Dose Level 2	VH4011499 Matching Placebo	Participants received a single dose of VH4011499 Dose Level 2 (medium concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
Part 1b: VH4011499 Dose Level 2	Antiretroviral therapy	Participants received a single dose of VH4011499 Dose Level 2 (medium concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
Matching placebo for VH4011499	Antiretroviral therapy	Participants received a matching placebo for VH4011499 on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
Part 2b: VH4011499 pre-specified dose	VH4011499	Participants received a single pre-specified dose of VH4011499 (high concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
Part 2b: VH4011499 pre-specified dose	Antiretroviral therapy	Participants received a single pre-specified dose of VH4011499 (high concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.

Primary Outcome Measures

Name	Time	Method
Monotherapy, VH4011499: Maximum Change From Baseline (Day 1) in Plasma HIV-1 RNA log10	From Baseline (Day 1) and up to Day 11	Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. Maximum change from baseline was calculated by subtracting the baseline value from the post-dose visit value when the plasma HIV-1 RNA reached its minimum level up to Day 11 (inclusive). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Monotherapy, VH4004280: Maximum Change From Baseline (Day 1) in Plasma HIV-1 Ribonucleic Acid (RNA) log10	From Baseline (Day 1) and up to Day 11	Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. Maximum change from baseline was calculated by subtracting the baseline value from the post-dose visit value when the plasma HIV-1 RNA reached its minimum level up to Day 11 (inclusive). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. The results were expressed as log10 copies per milliliter (log10 c/mL).

Secondary Outcome Measures

Name	Time	Method
Monotherapy: Number of Participants With Any Adverse Events (AEs)	From Baseline (Day 1) and up to Day 11	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any = occurrence of the event regardless of intensity grade or relation to the study intervention.
Follow-up: Number of Participants With Any AEs	From Day 11 and up to Day 39	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any = occurrence of the event regardless of intensity grade or relation to the study intervention.
Monotherapy: Number of Participants With AEs by Severity	From Baseline (Day 1) and up to Day 11	Severity was rated according to the Division of Acquired Immunodeficiency Syndrome (DAIDS) grading criteria, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death.
Follow-up: Number of Participants With AEs by Severity	From Day 11 and up to Day 39	Severity was rated according to the DAIDS grading criteria, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death.
Monotherapy: Number of Participants With AEs Leading to Study Treatment Discontinuation	From Baseline (Day 1) and up to Day 11	'Discontinuation' of study intervention refers to any participant who has not received all planned doses of study intervention.
Monotherapy and Follow-up, VH4004280: Change From Baseline for Liver Panel Laboratory Parameters - Total Bilirubin and Direct Bilirubin	At Baseline (Day 1) and at Days 2, 4, 6, 7, 9, 11, 18, 25, 32 and 39	Change from Baseline values for liver panel laboratory parameters total bilirubin and direct bilirubin were summarised. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.Standard deviation (SD) = 0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000.
Monotherapy and Follow-up, VH4011499: Change From Baseline for Liver Panel Laboratory Parameters - Total Bilirubin and Direct Bilirubin	At Baseline (Day 1) and at Days 2, 4, 6, 7, 9, 11, 18, 25, 32 and 39	Change from Baseline values for liver panel laboratory parameters total bilirubin and direct bilirubin were summarised. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value. SD = 0.0000 is defined as following: if all participants analyzed for a specific parameter at a specific time point have the same value, then SD is equal with 0.0000.
Monotherapy and Follow-up, VH4004280: Change From Baseline for Liver Panel Laboratory Parameters - Alanine Aminotransferace (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)	At Baseline (Day 1) and at Days 2, 4, 6, 7, 9, 11, 18, 25, 32 and 39	Change from Baseline values for liver panel laboratory parameters ALT, ALP and AST were summarised. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Monotherapy and Follow-up, VH4011499: Change From Baseline for Liver Panel Laboratory Parameters - ALT, ALP and AST	At Baseline (Day 1) and at Days 2, 4, 6, 7, 9, 11, 18, 25, 32 and 39	Change from Baseline values for liver panel laboratory parameters ALT, ALP and AST were summarised. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Monotherapy and Follow-up, VH4004280: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Laboratory Parameters - Total Bilirubin and Direct Bilirubin	From Baseline (Day 1) and up to Day 39	Laboratory abnormalities were graded according to DAIDS grading table Version 2.1 where grades were defined based on numeric criteria as follows Grade 0: participants with missing baseline values; Grade 1: Mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences.
Monotherapy and Follow-up, VH4011499: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Laboratory Parameters - Total Bilirubin and Direct Bilirubin	From Baseline (Day 1) and up to Day 39	Laboratory abnormalities were graded according to DAIDS grading table Version 2.1 where grades were defined based on numeric criteria as follows Grade 0: participants with missing baseline values; Grade 1: Mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences.
Monotherapy and Follow-up, VH4004280: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Laboratory Parameters - ALT, ALP and AST	From Baseline (Day 1) and up to Day 39	Laboratory abnormalities were graded according to DAIDS grading table Version 2.1 where grades were defined based on numeric criteria as follows Grade 0: participants with missing baseline values; Grade 1: Mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences.
Monotherapy and Follow-up, VH4011499: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Laboratory Parameters - ALT, ALP and AST	From Baseline (Day 1) and up to Day 39	Laboratory abnormalities were graded according to DAIDS grading table Version 2.1 where grades were defined based on numeric criteria as follows Grade 0: participants with missing baseline values; Grade 1: Mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences.
Monotherapy, VH4004280: Maximum Observed Plasma Drug Concentration (Cmax)	After dose administration at Day 1	Cmax is defined as the maximum concentration of the drug in plasma.
Monotherapy, VH4011499: Cmax	After dose administration at Day 1 and Day 6	Cmax is defined as the maximum concentration of the drug in plasma.
Monotherapy, VH4004280: Time to Maximum Observed Plasma Drug Concentration (Tmax)	After dose administration at Day 1	Tmax is a measure of the time required to reach the maximum concentration of the drug.
Monotherapy, VH4011499: Tmax	After dose administration at Day 1 and Day 6	Tmax is a measure of the time required to reach the maximum concentration of the drug.
Monotherapy, VH4004280: Plasma Concentration at Day 11 (C11)	At Day 11	C11 is defined as the concentration of the drug in plasma at Day 11.
Monotherapy, VH4011499: C11	At Day 11	C11 is defined as the concentration of the drug in plasma at Day 11.
Monotherapy, VH4004280: Change in Plasma HIV-1 RNA From Baseline	At Baseline (Day 1) and Day 11	Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.
Monotherapy, VH4011499: Change in Plasma HIV-1 RNA From Baseline	At Baseline (Day 1) and Day 11	Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from baseline was calculated by subtracting the baseline value from the post-dose visit value.