VH3739937 Phase 1 Multiple Ascending Dose (MAD) Study in Healthy Volunteers Including Relative Bioavailability (RBA), Optional Food Effect (FE), and Drug-drug Interaction (DDI)

NCT06533280 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 221773
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study will assess safety, tolerability and pharmacokinetic (PK) of VH3739937 in healthy participants.

Conditions

HIV Infections

Keywords

VH3739937; Multiple ascending dose; Relative bioavailability; Food effect; Drug-drug interaction

Outcome Measures

Primary Outcomes (20)

• Part A: Number of participants with any adverse events (AEs)

  Up to Day 25 for Cohorts A1 and A2 and Day 30 for Cohort A3

• Part B: Number of participants with any adverse events (AEs)

  Up to Day 15

• Part C: Number of participants with any adverse events (AEs)

  Up to Day 42

• Part D: Number of participants with any adverse events (AEs)

  Up to Day 28

• Part A: Number of participants with adverse events (AEs) by grade of severity

  The severity grade is defined as following: Grade 1= mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threatening.

  Up to Day 25 for Cohorts A1 and A2, and Day 30 for Cohort A3

• Part B: Number of participants with adverse events (AEs) by grade of severity

  The severity grade is defined as following: Grade 1= mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threatening.

  Up to Day 15 (Periods 2 and 4 only)

• Part C: Number of participants with adverse events (AEs) by grade of severity

  The severity grade is defined as following: Grade 1= mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threatening.

  Up to Day 42

• Part D: Number of participants with adverse events (AEs) by grade of severity

  The severity grade is defined as following: Grade 1= mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threatening.

  Up to Day 28

• Part A: Number of participants with any serious adverse events (SAEs)

  Up to Day 25 for Cohort A1 and A2 and Day 30 for Cohort A3

• Part B: Number of participants with any serious adverse events (SAEs)

  Up to Day 15 (Periods 2 and 4 only)

• Part C: Number of participants with any serious adverse events (SAEs)

  Up to Day 42

• Part D: Number of participants with any serious adverse events (SAEs)

  Up to Day 28

• Part A: Number of participants with serious adverse events (SAEs) by grade of severity

  The severity grade is defined as following: Grade 1= mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threatening.

  Up to Day 25 for Cohort A1 and A2, and Day 30 for Cohort A3

• Part B: Number of participants with serious adverse events (SAEs) by grade of severity

  The severity grade is defined as following: Grade 1= mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threatening.

  Up to Day 15 (Periods 2 and 4 only)

• Part C: Number of participants with serious adverse events (SAEs) by grade of severity

  The severity grade is defined as following: Grade 1= mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threatening.

  Up to Day 42

• Part D: Number of participants with serious adverse events (SAEs) by grade of severity

  The severity grade is defined as following: Grade 1= mild, Grade 2=moderate, Grade 3=severe, Grade 4=potentially life-threatening.

  Up to Day 28

• Part B: Area under the plasma concentration over a dosing interval from time of dosing to the time of the subsequent dose (AUC[0-t])

  At Days 1 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)

• Part B: AUC time curve from time zero to infinity (AUC[0-infinity])

  At Days 1 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)

• Part B: Time to maximum observed plasma concentration (Tmax)

  At Days 1 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)

• Part B: Maximum observed plasma concentration (Cmax) after VH3739937 administration

  At Days 1 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)

Secondary Outcomes (32)

• Part B: AUC to the end of the dosing period (AUC[0-tau]) after VH3739937 administration

  At Days 1, 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)

• Part B: AUC[0-infinity] after VH3739937 administration

  At Days 1, 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)

• Part B: Tmax after VH3739937 administration

  At Days 1, 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)

• Part B: Apparent terminal half-life (T1/2) after VH3739937 administration

  At Days 1, 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)

• Part B: Apparent Oral Clearance (CL/F) after VH3739937 administration

  At Days 1, 2, 3, 4, 6, 8, 12, 15 (Period 2 and Period 3 only)

Study Arms (6)

Part A MAD: VH3739937

EXPERIMENTAL

Part A MAD: VH3739937 group will contain 3 ascending repeat-dose cohorts (Cohorts A1- A3), where participants will receive a twice daily (BID) dose of VH3739937 for 1 (Cohort A1), 2 (Cohort A2) or 3 (Cohort A3) days in fed conditions.

Drug: Part A, C and D: VH3739937 500 mg; Drug: Part A: VH3739937 100 mg

Part A MAD: Placebo

PLACEBO COMPARATOR

Part A MAD: Placebo group will include participants that will receive BID dose of placebo in fed conditions

Drug: Part A and C: Placebo

Part B RBA/ optional FE: VH3739937

EXPERIMENTAL

Part B RBA/FE: VH3739937 group will include participants that will receive treatment sequences (Treatment AB or BA) alternatively in Period 1 and Period 2 of the treatment. In Period 3 and Period 4, participants will receive 1 of 6 treatment sequences (CD, CE, ED, EC, DE, DC) in fed or fasted conditions.

Drug: Part B: Treatment A; Drug: Part B: Treatment B; Drug: Part B: Treatment C; Drug: Part B: Treatment D; Drug: Part B: Treatment E

Part C: Optional QW VH3739937

EXPERIMENTAL

Participants in this group will receive a weekly administration (QW) of VH3739937 during a 3-week period in fed conditions.

Drug: Part A, C and D: VH3739937 500 mg

Part C: Optional QW Placebo

PLACEBO COMPARATOR

Participants in this group will receive a weekly administration (QW) of placebo during a 3-week period in fed conditions.

Drug: Part A, C and D: VH3739937 500 mg; Drug: Part A and C: Placebo

Part D: Optional DDI

EXPERIMENTAL

Participants in this group will receive a dose of the probe cocktail (Midazolam, Digoxin, Total Dabigatran etexilate, Rosuvastatin) alone on Day 1, followed by a subsequent dose of probe cocktail together with a single dose of VH3739937 on Day 10, in fed conditions.

Drug: Part A, C and D: VH3739937 500 mg; Drug: Part D: Probe cocktail

Interventions

Part A, C and D: VH3739937 500 mg DRUG

Oral administration of VH3739937 in moderate fat/moderate calorie conditions

Part A MAD: VH3739937; Part C: Optional QW Placebo; Part C: Optional QW VH3739937; Part D: Optional DDI

Part A: VH3739937 100 mg DRUG

Oral administration of VH3739937 in moderate fat/moderate calorie conditions.

Part A MAD: VH3739937

Part A and C: Placebo DRUG

Oral administration of Placebo in moderate fat/moderate calorie conditions

Part A MAD: Placebo; Part C: Optional QW Placebo

Part B: Treatment A DRUG

VH3739937, 500 mg(single dose given as 5 x 100 mg tablets). administered under moderate fat/moderate calorie conditions (reference)

Part B RBA/ optional FE: VH3739937

Part B: Treatment B DRUG

VH3739937, 500 mg (single dose given as 500 mg tablet) administered under moderate fat/moderate calorie conditions (test)

Part B RBA/ optional FE: VH3739937

Part B: Treatment C DRUG

VH3739937, 500 mg single tablet administered under fasted conditions.

Part B RBA/ optional FE: VH3739937

Part B: Treatment D DRUG

VH3739937, 500 mg single tablet administered under low-fat/ low calorie conditions.

Part B RBA/ optional FE: VH3739937

Part B: Treatment E DRUG

VH3739937, 500 mg single tablet administered under high-fat/ high calorie conditions.

Part B RBA/ optional FE: VH3739937

Part D: Probe cocktail DRUG

Oral administration of probe cocktail (Midazolam, Digoxin, Total Dabigatran etexilate, Rosuvastatin) in moderate fat/moderate calorie conditions.

Part D: Optional DDI

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants who are overtly healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and ECG).
• Participants who can understand and comply with protocol requirements and timetables, instructions, and protocol-stated restrictions.
• Age
• Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
• Weight
• Body weight \>=50.0 kg (110 lbs) for men and \>=45.0 kg (99 lbs) for women, and BMI within the range 18.5 to 32.0 kg/m2 (inclusive).
• Sex
• Participants male at birth and participants female at birth:
• Participants male at birth:
• Participants male at birth are eligible to participate if they agree to the following during the study intervention period and for at least 90 days (a spermatogenesis cycle) after the last dose of study intervention:
• Refrain from donating sperm
• PLUS either:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent.
• Must agree to use contraception as detailed below: Agree to use a male condom and, if their partner is a person who is able to become pregnant, and who is not currently pregnant, they should also be advised of the benefit for their partner to use a highly effective method of contraception when having sexual intercourse, as a condom may break or leak.
• Participants female at birth:

You may not qualify if:

• Medical conditions
• History or presence of cardiovascular, respiratory, hepatic, renal, GI, endocrine, hematologic, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of data.
• Unstable liver disease known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per Investigator assessment).
• Known history of cirrhosis with or without viral hepatitis co-infection.
• History of clinically relevant hepatitis within last 6 months.
• Patients with chronic hepatitis B (HBsAg positive) infection (see HBV diagnostic criteria described below and in the study laboratory manual).
• Have a history of malignant neoplasm (excepting definitively treated non-melanoma skin cancer or carcinoma in situ of the uterine cervix, which may be enrolled at any time) within the last 5 years.
• Clinically significant cardiovascular disease.
• A sustained semi-supine systolic blood pressure \>150 mm Hg or \<90 mm Hg or a semi-supine diastolic blood pressure \>95 mm Hg or \<50 mm Hg at Screening or Check-in.
• A resting HR of \<50 bpm or \>100 bpm when vital signs are measured at Screening or Check-in. A HR from 100 bpm to 110 bpm can be rechecked by ECG or vital signs within up to 2 hours to verify eligibility.
• An uninterpretable ECG or any significant arrhythmia or ECG finding which, in the opinion of the Investigator or VH/GSK Medical Monitor, will interfere with the safety of the individual participant.
• Abnormalities on Screening ECG is allowed for eligibility determination: QTcF \> 450 msec., QRS \> 120 msec, PR \> 220 msec
• Any history of significant underlying psychiatric disorder, in the opinion of the Investigator or Medical Monitor; or a clinical assessment of suicidality based on the responses on the C-SSRS (Columbia Suicidality Scale). Participants' history of suicidal behaviour and/or suicidal ideation should be considered when evaluating for suicide risk.
• Any history of major depressive disorder with or without suicidal features, or anxiety disorders that required medical intervention such as hospitalization or other inpatient treatment and/or chronic (\>6 months) outpatient treatment. Participants with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy (\<6 months) without inpatient treatment and are currently well-controlled clinically or resolved may be considered for entry after discussion and agreement with the VH/GSK Medical Monitor.
• Any pre-existing physical or other psychiatric condition which could interfere with the participant's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the participant.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (1)

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blind (sponsor-unblinded) study.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2024
• First Posted: August 1, 2024
• Study Start: August 2, 2024
• Primary Completion: August 14, 2024
• Study Completion: August 14, 2024
• Last Updated: April 22, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.

Locations

US (1)