First-Time-in-Human (FTIH) Study to Evaluate the Safety, Tolerability and Pharmacokinetics (PK) of VH4011499 in Healthy Participants

ViiV Healthcare

Status and phase

Completed

Phase 1

Conditions

HIV Infections

Treatments

Drug: VH4011499

Drug: Placebo

Drug: Midazolam

Study type

Interventional

Funder types

Industry

Identifiers

NCT05393271

218490

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 VH4011499 in healthy adults. The study will be conducted in 3 parts: Part 1 will investigate single ascending doses (SAD) and Part 2 will investigate multiple ascending doses (MAD). Part 3 will investigate single dose of a new formulation of VH4011499. The transition from SAD to MAD will be based on the assessment of the Safety and Dose Escalation Committee.

Enrollment

73 patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Participants who are overtly healthy.
Participants must have two consecutive Severe Acute Respiratory Syndrome Coronavirus 2 (SARs-CoV-2) Polymerase chain reaction (PCR) negative results prior to dosing.
Participants must have body weight > 50 kilograms (kg) and body mass index (BMI) within the range 19-32 kilograms per meter square (kg/m^2).
Male or female participants (either of non-childbearing potential or of child-bearing potential and using acceptable contraception).
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.
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 within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to dosing and for the duration of the study, unless in the opinion of the Investigator and Sponsor, the medication will not interfere with the study medications, procedures, or compromise participant safety.
Live vaccine(s) within 1 month prior to screening or plans to receive such vaccines during the study.
Exposure to more than 4 investigational products within 12 months prior to dosing.
Current enrollment or recent 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 within 14 days.
Positive HIV antibody test.
Use 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 midazolam, excipients contained therein, benzodiazepines, or drug or other allergy that, contraindicates participation in the study.

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-a-bottle (PiB)

Placebo Comparator group

Description:

Healthy participants were given a single dose of placebo on Day 1 and were followed up until Day 28.

Treatment:

Drug: Placebo

Part 1 (SAD): VH4011499 25 mg PiB

Placebo Comparator group

Description:

Healthy participants were given a single dose of 25 mg VH4011499 on Day 1 and were followed up until Day 28.

Treatment:

Drug: VH4011499

Part 1 (SAD): VH4011499 125 mg PiB

Experimental group

Description:

Healthy participants were given a single dose of 125 mg VH4011499 on Day 1 and were followed up until Day 28.

Treatment:

Drug: VH4011499

Part 1 (SAD): VH4011499 200 mg PiB

Experimental group

Description:

Healthy participants were given a single dose of 200 mg VH4011499 on Day 1 and were followed up until Day 28.

Treatment:

Drug: VH4011499

Part 1 (SAD): VH4011499 625 mg PiB

Experimental group

Description:

Healthy participants were given a single dose of 625 mg VH4011499 on Day 1 and were followed up until Day 28.

Treatment:

Drug: VH4011499

Part 1 (SAD): VH4011499 1875 mg PiB

Experimental group

Description:

Healthy participants were given a single dose of 1875 mg VH4011499 on Day 1 and were followed up until Day 28.

Treatment:

Drug: VH4011499

Part 2 Multiple Ascending Dose (MAD): Placebo PiB

Placebo Comparator group

Description:

Healthy participants were given a dose of placebo once daily for a 14-day period and were followed up until Day 42.

Treatment:

Drug: Placebo

Part 2 (MAD): VH4011499 200 mg PiB

Experimental group

Description:

Healthy participants were given a dose of VH4011499 200 mg PiB once daily for a 14-day period and were followed up until Day 42.

Treatment:

Drug: VH4011499

Part 2 (MAD): VH4011499 300 mg + Midazolam (MDZ) PiB

Experimental group

Description:

Healthy participants were given a dose of VH4011499 300 mg once daily and a single dose of Midazolam on Days 1, 2, and 15, and were followed up until Day 42.

Treatment:

Drug: Midazolam

Drug: VH4011499

Part 2 (MAD): VH4011499 400 mg PiB

Experimental group

Description:

Healthy participants were given a dose of VH4011499 400 mg PiB once daily for a 14-day period and were followed up until Day 42.

Treatment:

Drug: VH4011499

Part 3 (Single dose): VH4011499 200 mg tablet

Experimental group

Description: