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

ViiV Healthcare44 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

HIV Infections

Interventions

VH4004280DRUG

VH4004280 was administered as tablets orally at Day 1.

VH4011499DRUG

VH4011499 was administered as tablets orally at Day 1 and Day 6.

VH4004280 Matching PlaceboDRUG

VH4004280 Matching Placebo was administered as tablets orally at Day 1.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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.

Locations (20)

GSK Investigational Site

Bakersfield, California, United States

GSK Investigational Site

DeLand, Florida, United States

Outcomes

Primary Outcomes

Monotherapy, VH4004280: Maximum Change From Baseline (Day 1) in Plasma HIV-1 Ribonucleic Acid (RNA) log10

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).

Time frame: From Baseline (Day 1) and up to Day 11

Monotherapy, VH4011499: Maximum Change From Baseline (Day 1) in Plasma HIV-1 RNA log10

Time frame: From Baseline (Day 1) and up to Day 11

Secondary Outcomes

Monotherapy: Number of Participants With Any Adverse Events (AEs)

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.

Time frame: From Baseline (Day 1) and up to Day 11

Follow-up: Number of Participants With Any AEs

Time frame: From Day 11 and up to Day 39

Data from ClinicalTrials.gov

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VH4011499 Matching Placebo was administered as tablets orally at Day 1 and Day 6.

Antiretroviral therapyDRUG

Antiretroviral therapy was administered as available and as per investigator's recommendation.

GSK Investigational Site

Newark, New Jersey, United States

GSK Investigational Site

Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, Argentina

GSK Investigational Site

Ciudad Autonoma de Bueno, Argentina

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Marseille, France

GSK Investigational Site

Nantes, France

...and 10 more locations

Monotherapy: Number of Participants With AEs by Severity

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.

Time frame: From Baseline (Day 1) and up to Day 11

Follow-up: Number of Participants With AEs by Severity

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.

Time frame: From Day 11 and up to Day 39

Monotherapy: Number of Participants With AEs Leading to Study Treatment Discontinuation

'Discontinuation' of study intervention refers to any participant who has not received all planned doses of study intervention.

Time frame: From Baseline (Day 1) and up to Day 11

Monotherapy and Follow-up, VH4004280: Change From Baseline for Liver Panel Laboratory Parameters - Total Bilirubin and Direct Bilirubin

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.

Time frame: At Baseline (Day 1) and at Days 2, 4, 6, 7, 9, 11, 18, 25, 32 and 39

Monotherapy and Follow-up, VH4011499: Change From Baseline for Liver Panel Laboratory Parameters - Total Bilirubin and Direct Bilirubin

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.

Time frame: At Baseline (Day 1) and at Days 2, 4, 6, 7, 9, 11, 18, 25, 32 and 39

Monotherapy and Follow-up, VH4004280: Change From Baseline for Liver Panel Laboratory Parameters - Alanine Aminotransferace (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)

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.

Time frame: At Baseline (Day 1) and at Days 2, 4, 6, 7, 9, 11, 18, 25, 32 and 39

Monotherapy and Follow-up, VH4011499: Change From Baseline for Liver Panel Laboratory Parameters - ALT, ALP and AST

Time frame: At Baseline (Day 1) and at Days 2, 4, 6, 7, 9, 11, 18, 25, 32 and 39

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

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.

Time frame: From Baseline (Day 1) and up to Day 39

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

Time frame: From Baseline (Day 1) and up to Day 39

Monotherapy and Follow-up, VH4004280: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Laboratory Parameters - ALT, ALP and AST

Time frame: From Baseline (Day 1) and up to Day 39

Monotherapy and Follow-up, VH4011499: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Laboratory Parameters - ALT, ALP and AST

Time frame: From Baseline (Day 1) and up to Day 39

Monotherapy, VH4004280: Maximum Observed Plasma Drug Concentration (Cmax)

Cmax is defined as the maximum concentration of the drug in plasma.

Time frame: After dose administration at Day 1

Monotherapy, VH4011499: Cmax

Cmax is defined as the maximum concentration of the drug in plasma.

Time frame: After dose administration at Day 1 and Day 6

Monotherapy, VH4004280: Time to Maximum Observed Plasma Drug Concentration (Tmax)

Tmax is a measure of the time required to reach the maximum concentration of the drug.

Time frame: After dose administration at Day 1

Monotherapy, VH4011499: Tmax

Tmax is a measure of the time required to reach the maximum concentration of the drug.

Time frame: After dose administration at Day 1 and Day 6

Monotherapy, VH4004280: Plasma Concentration at Day 11 (C11)

C11 is defined as the concentration of the drug in plasma at Day 11.

Time frame: At Day 11

Monotherapy, VH4011499: C11

C11 is defined as the concentration of the drug in plasma at Day 11.

Time frame: At Day 11

Monotherapy, VH4004280: Change in Plasma HIV-1 RNA From Baseline

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.

Time frame: At Baseline (Day 1) and Day 11

Monotherapy, VH4011499: Change in Plasma HIV-1 RNA From Baseline

Time frame: At Baseline (Day 1) and Day 11