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First-Time-in-Human (FTIH) Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of VH4004280 in Healthy Participants

Primary Purpose

HIV Infections

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

VH4004280

Placebo

Midazolam

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring First-time-in-human, GSK4004280, VH4004280, HIV-1 capsid inhibitor, Single ascending doses, Multiple ascending doses

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion criteria:

Participant must be 18 to 50 years of age inclusive.
Participants who are overtly healthy.
Male or female participants of non-childbearing potential.
Capable of giving signed informed consent.

Exclusion criteria:

History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, neurological or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study drug or interfering with the interpretation of data.
Abnormal blood pressure.
Symptomatic herpes zoster.
Evidence of active or latent tuberculosis (TB).
Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
Breast cancer within the past 10 years.
Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
QT interval corrected for heart rate according to Fridericia's formula (QTcF) greater than (>)450 milliseconds (msec).
Past or intended use of over-the-counter or prescription medication including herbal medications.
Live vaccine(s) within 1 month prior to screening or plans to receive such vaccines during the study.
Exposure to more than 4 new investigational products within 12 months prior to the first dosing day.
Current enrollment or past participation in another investigational study.
ALT >1.5 times upper limit of normal (ULN), total bilirubin >1.5 times ULN, and/or estimated serum creatinine clearance less than 60 milliliters per minute.
History of or current infection with hepatitis B or hepatitis C.
Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test, having signs and symptoms, or having contact with known Coronavirus Disease-2019 (COVID-19) positive person/s.
Positive HIV antibody test.
User of tobacco or nicotine-containing products, regular alcohol consumption and/or regular use of known drugs of abuse.
Sensitivity to the study drug, or components thereof.

Sites / Locations

GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Arm Label

Part 1 (SAD): Participants receiving VH4004280

Part 1 (SAD): Participants receiving placebo

Part 2 (MAD) Non Drug-Drug Interaction (DDI) cohort: Participants receiving VH4004280

Part 2 (MAD) Non DDI cohort: Participants receiving placebo

Part 2 (MAD) DDI cohort: Participants receiving VH4004280 and Midazolam

Part 2 (MAD) DDI cohort: Participants receiving Placebo and Midazolam

Part 3 (Single dose): Participants receiving VH4004280 (new formulation)

Arm Description

Outcomes

Primary Outcome Measures

Part 1: Number of participants with adverse events (AEs)

Part 2: Number of participants with AEs

Part 3: Number of participants with AEs

Part 1: Number of participants with AEs by severity

Part 2: Number of participants with AEs by severity

Part 3: Number of participants with AEs by severity

Part 2: Percentage of participants discontinuing treatment due to AEs

Part 1: Absolute values of liver panel parameters: Direct and total bilirubin (Micromoles per liter)

Part 1: Absolute values of liver panel parameters: Alanine aminotransferase (ALT), Alkaline phosphatase (ALP) and Aspartate aminotransferase (AST) (International units per Liter)

Part 2: Absolute values of liver panel parameters: Direct and total bilirubin (Micromoles per liter)

Part 2: Absolute values of liver panel parameters: ALT, ALP and AST (International units per Liter)

Part 3: Absolute values of liver panel parameters: Direct and total bilirubin (Micromoles per liter)

Part 3: Absolute values of liver panel parameters: ALT, ALP and AST (International units per Liter)

Part 1: Change from Baseline in liver panel parameters: Direct and total bilirubin (Micromoles per liter)

Part 1: Change from Baseline in liver panel parameters: ALT, ALP and AST (International units per Liter)

Part 2: Change from Baseline in liver panel parameters: Direct and total bilirubin (Micromoles per liter)

Part 2: Change from Baseline in liver panel parameters: ALT, ALP and AST (International units per Liter)

Part 3: Change from Baseline in liver panel parameters: Direct and total bilirubin (Micromoles per liter)

Part 3: Change from Baseline in liver panel parameters: ALT, ALP and AST (International units per Liter)

Part 1: Percentage of participants with maximum toxicity grade increase from Baseline for liver panel parameters

Part 2: Percentage of participants with maximum toxicity grade increase from Baseline for liver panel parameters

Part 3: Percentage of participants with maximum toxicity grade increase from Baseline for liver panel parameters

Part 1: Area under the plasma concentration time curve from time zero to infinity (AUC[0-infinity]) following single dose administration of VH4004280

Part 2: Area under the plasma concentration time curve over a dosing interval from time of dosing to the time of the subsequent dose (AUC[0-tau]) following repeat dose administration of VH4004280

Part 1: Maximum observed plasma concentration (Cmax) following single dose administration of VH4004280

Part 1: Time to maximum observed plasma concentration (Tmax) and Apparent terminal half-life (T1/2) following single dose administration of VH4004280 (Hours)

Part 2: Cmax following repeat dose administration of VH4004280

Part 2: Tmax and T1/2 following repeat dose administration of VH4004280 (Hours)

Secondary Outcome Measures

Full Information

NCT ID

NCT05163522

First Posted

December 6, 2021

Last Updated

August 29, 2023

Sponsor

ViiV Healthcare

1. Study Identification

Unique Protocol Identification Number

NCT05163522

Brief Title

First-Time-in-Human (FTIH) Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of VH4004280 in Healthy Participants

Official Title

A Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Orally Administered VH4004280 in Healthy Participants

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Completed

Study Start Date

December 13, 2021 (Actual)

Primary Completion Date

June 21, 2023 (Actual)

Study Completion Date

June 21, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ViiV Healthcare

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This FTIH study aims to evaluate the safety, tolerability and PK of the novel investigational Human immunodeficiency virus (HIV)-1 capsid inhibitor VH4004280 in healthy adults. The study will be conducted in 3 parts: Part 1 will investigate single ascending doses (SAD), Part 2 will investigate multiple ascending doses and drug-drug interaction (MAD/MAD DDI) Part 3 will investigate single dose relative bioavailability (RBA) of a new formulation of VH4004280.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections

Keywords

First-time-in-human, GSK4004280, VH4004280, HIV-1 capsid inhibitor, Single ascending doses, Multiple ascending doses

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

ParticipantInvestigator

Masking Description

This is a double-blind (sponsor unblinded) study.

Allocation

Randomized

Enrollment

73 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1 (SAD): Participants receiving VH4004280

Arm Type

Experimental

Arm Title

Part 1 (SAD): Participants receiving placebo

Arm Type

Placebo Comparator

Arm Title

Part 2 (MAD) Non Drug-Drug Interaction (DDI) cohort: Participants receiving VH4004280

Arm Type

Experimental

Arm Title

Part 2 (MAD) Non DDI cohort: Participants receiving placebo

Arm Type

Placebo Comparator

Arm Title

Part 2 (MAD) DDI cohort: Participants receiving VH4004280 and Midazolam

Arm Type

Experimental

Arm Title

Part 2 (MAD) DDI cohort: Participants receiving Placebo and Midazolam

Arm Type

Placebo Comparator

Arm Title

Part 3 (Single dose): Participants receiving VH4004280 (new formulation)

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

VH4004280

Other Intervention Name(s)

GSK4004280

Intervention Description

VH4004280 will be administered.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo will be administered.

Intervention Type

Drug

Intervention Name(s)

Midazolam

Intervention Description

Midazolam will be administered

Primary Outcome Measure Information:

Title

Part 1: Number of participants with adverse events (AEs)

Time Frame

Up to Day 49

Title

Part 2: Number of participants with AEs

Time Frame

Up to Day 63

Title

Part 3: Number of participants with AEs

Time Frame

Up to Day 49

Title

Part 1: Number of participants with AEs by severity

Time Frame

Up to Day 49

Title

Part 2: Number of participants with AEs by severity

Time Frame

Up to Day 63

Title

Part 3: Number of participants with AEs by severity

Time Frame

Up to Day 49

Title

Part 2: Percentage of participants discontinuing treatment due to AEs

Time Frame

Up to Day 14

Title

Part 1: Absolute values of liver panel parameters: Direct and total bilirubin (Micromoles per liter)

Time Frame

Up to Day 49

Title

Part 1: Absolute values of liver panel parameters: Alanine aminotransferase (ALT), Alkaline phosphatase (ALP) and Aspartate aminotransferase (AST) (International units per Liter)

Time Frame

Up to Day 49

Title

Part 2: Absolute values of liver panel parameters: Direct and total bilirubin (Micromoles per liter)

Time Frame

Up to Day 63

Title

Part 2: Absolute values of liver panel parameters: ALT, ALP and AST (International units per Liter)

Time Frame

Up to Day 63

Title

Part 3: Absolute values of liver panel parameters: Direct and total bilirubin (Micromoles per liter)

Time Frame

Up to Day 49

Title

Part 3: Absolute values of liver panel parameters: ALT, ALP and AST (International units per Liter)

Time Frame

Up to Day 49

Title

Part 1: Change from Baseline in liver panel parameters: Direct and total bilirubin (Micromoles per liter)

Time Frame

Baseline and up to Day 49

Title

Part 1: Change from Baseline in liver panel parameters: ALT, ALP and AST (International units per Liter)

Time Frame

Baseline and up to Day 49

Title

Part 2: Change from Baseline in liver panel parameters: Direct and total bilirubin (Micromoles per liter)

Time Frame

Baseline and up to Day 63

Title

Part 2: Change from Baseline in liver panel parameters: ALT, ALP and AST (International units per Liter)

Time Frame

Baseline and up to Day 63

Title

Part 3: Change from Baseline in liver panel parameters: Direct and total bilirubin (Micromoles per liter)

Time Frame

Baseline and up to Day 49

Title

Part 3: Change from Baseline in liver panel parameters: ALT, ALP and AST (International units per Liter)

Time Frame

Baseline and up to Day 49

Title

Part 1: Percentage of participants with maximum toxicity grade increase from Baseline for liver panel parameters

Time Frame

Up to Day 49

Title

Part 2: Percentage of participants with maximum toxicity grade increase from Baseline for liver panel parameters

Time Frame

Up to Day 63

Title

Part 3: Percentage of participants with maximum toxicity grade increase from Baseline for liver panel parameters

Time Frame

Up to Day 49

Title

Part 1: Area under the plasma concentration time curve from time zero to infinity (AUC[0-infinity]) following single dose administration of VH4004280

Time Frame

Up to Day 49

Title

Part 2: Area under the plasma concentration time curve over a dosing interval from time of dosing to the time of the subsequent dose (AUC[0-tau]) following repeat dose administration of VH4004280

Time Frame

Up to Day 63

Title

Part 1: Maximum observed plasma concentration (Cmax) following single dose administration of VH4004280

Time Frame

Up to Day 49

Title

Part 1: Time to maximum observed plasma concentration (Tmax) and Apparent terminal half-life (T1/2) following single dose administration of VH4004280 (Hours)

Time Frame

Up to Day 49

Title

Part 2: Cmax following repeat dose administration of VH4004280

Time Frame

Up to Day 63

Title

Part 2: Tmax and T1/2 following repeat dose administration of VH4004280 (Hours)

Time Frame

Up to Day 63

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: Participant must be 18 to 55 years of age inclusive. Participants who are overtly healthy. Male or female participants of non-childbearing potential. Capable of giving signed informed consent. Exclusion criteria: History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, neurological or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study drug or interfering with the interpretation of data. Abnormal blood pressure. Symptomatic herpes zoster. Evidence of active or latent tuberculosis (TB). Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years. Breast cancer within the past 10 years. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). QT interval corrected for heart rate according to Fridericia's formula (QTcF) greater than (>)450 milliseconds (msec). Past or intended use of over-the-counter or prescription medication including herbal medications. Live vaccine(s) within 1 month prior to screening or plans to receive such vaccines during the study. Exposure to more than 4 new investigational products within 12 months prior to the first dosing day. Current enrollment or past participation in another investigational study. ALT >1.5 times upper limit of normal (ULN), total bilirubin >1.5 times ULN, and/or estimated serum creatinine clearance less than 60 milliliters per minute. History of or current infection with hepatitis B or hepatitis C. Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test, having signs and symptoms, or having contact with known Coronavirus Disease-2019 (COVID-19) positive person/s. Positive HIV antibody test. User of tobacco or nicotine-containing products, regular alcohol consumption and/or regular use of known drugs of abuse. Sensitivity to the study drug, or components thereof.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

ViiV Healthcare

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89113

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

IPD for this study will be made available via the Clinical Study Data Request site.

IPD Sharing Time Frame

IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.

IPD Sharing Access Criteria

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

IPD Sharing URL

http://clinicalstudydatarequest.com

Learn more about this trial

First-Time-in-Human (FTIH) Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of VH4004280 in Healthy Participants

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