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

ViiV Healthcare

Status and phase

Completed

Phase 1

Conditions

HIV Infections

Treatments

Drug: VH4004280

Drug: Midazolam

Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT05163522

217058

Details and patient eligibility

About

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.

Enrollment

73 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Sequential Assignment

Masking

Double Blind

73 participants in 11 patient groups, including a placebo group

Part 1 Single Ascending Dose (SAD): Placebo Powder-in-bottle (PiB)

Placebo Comparator group

Description:

Healthy participants were given a single oral dose of placebo on Day 1 and were followed up to approximately Day 49.

Treatment:

Drug: Placebo

Part 1 (SAD): VH4004280 10 mg PiB

Experimental group

Description:

Healthy participants were given a single oral dose of 10 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.

Treatment:

Drug: VH4004280

Part 1 (SAD): VH4004280 50 mg PiB

Experimental group

Description:

Healthy participants were given a single oral dose of 50 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.

Treatment:

Drug: VH4004280

Part 1 (SAD): VH4004280 150 mg PiB

Experimental group

Description:

Healthy participants were given a single oral dose of 150 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.

Treatment:

Drug: VH4004280

Part 1 (SAD): VH4004280 450 mg PiB

Experimental group

Description:

Healthy participants were given a single oral dose of 450 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.

Treatment:

Drug: VH4004280

Part 1 (SAD): VH4004280 900 mg PiB

Experimental group

Description:

Healthy participants were given a single oral dose of 900 mg VH4004280 PiB on Day 1 and were followed up to approximately Day 49.

Treatment:

Drug: VH4004280

Part 2 Multiple Ascending Dose (MAD): Placebo PiB

Placebo Comparator group

Description:

Healthy participants were given a dose of placebo once daily (QD) for a 14-day period and were followed up to approximately Day 63.

Treatment:

Drug: Placebo

Part 2 (MAD): VH4004280 100 mg PiB

Experimental group

Description:

Healthy participants were given a dose of 100 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.

Treatment:

Drug: VH4004280

Part 2 (MAD): VH4004280 250 mg + Midazolam (MDZ) PiB

Experimental group

Description:

Healthy participants were given a dose of 250 mg VH4004280 PiB QD for a 14-day period, and a single dose of Midazolam on days 1, 2, and 15, and were followed up to approximately Day 63.

Treatment:

Drug: Midazolam

Drug: VH4004280

Part 2 (MAD): VH4004280 350 mg PiB

Experimental group

Description:

Healthy participants were given a dose of 350 mg VH4004280 PiB QD for a 14-day period and were followed up to approximately Day 63.

Treatment:

Drug: VH4004280

Part 3 (Single dose): VH4004280 450 mg tablet

Experimental group

Description: