PH2a, VH4524184 Proof-of-Concept in Treatment-Naïve Adults Living with HIV-1

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Viiv Healthcare UK Limited, Viiv Healthcare UK Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

9 Apr 2024 → 12 Jul 2024

Decision date (initial)

2024-04-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ViiV Healthcare UK Ltd

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Efficacy, Pharmacokinetic, Safety, Others

To evaluate the antiviral activity of VH4524184 in Treatment Naïve participants with HIV-1 during 10 days of monotherapy

Secondary objectives 5

1. To assess the safety and tolerability of VH4524184
2. To characterize the pharmacokinetic profile of VH4524184
3. To evaluate any relationship between VH4524184 exposure and change in plasma HIV-1 RNA (Ribonucleic Acid)
4. To assess the occurrence of emergent genotypic or phenotypic resistance after 10 days of monotherapy with VH4524184
5. To assess the immunologic effects of VH4524184 when administered over 10 days in participants living with HIV Objective

Conditions and MedDRA coding

HIV Infections

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Participant must be 18 to 65 years of age inclusive at the time of signing the informed consent.
2. Participants who are overtly healthy (other than HIV infection) as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
3. Positive HIV antibody test
4. Documented HIV infection and Screening plasma HIV-1 RNA ≥ 3,000 copies/mL. A single repeat of this test is allowed within a single Screening period to determine eligibility.
5. Screening CD4+ T-cell count ≥200 cells/mm3
6. Treatment-naïve: No antiretrovirals (ARVs, in combination or monotherapy) received after the diagnosis of HIV-1 infection.
7. HIV Pre-exposure or post-exposure prophylaxis: No prior use of any INSTI (including cabotegravir) for HIV pre-exposure or post-exposure prophylaxis.
8. Body weight ≥50.0 kg (110 lbs.) for men and ≥45.0 kg (99 lbs) for women and BMI within the range 18.5-31.0 kg/m2 (inclusive - applies to males and females).
9. A participant of childbearing potential must have a negative serum hCG test at screening, and negative urine hCG test at Day 1, before the first dose of study intervention.
10. If a urine test cannot be confirmed as negative (e.g. ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
11. The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease risk for inclusion of a female with an early undetected pregnancy.
12. Capable of giving signed informed consent
13. Participant must be willing and able to start standard-of-care ART as selected with the investigator on Study Day 10.

Exclusion criteria 18

1. Participants with primary HIV infection.
2. Any evidence of an active CDC Stage 3 disease, except cutaneous Kaposi’s sarcoma not requiring systemic therapy during the study.
3. Untreated syphilis infection [positive RPR at screen] without documentation of treatment.
4. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; or other localized malignancies
5. Any pre-existing physical or mental condition which, in the opinion of the Investigator, may interfere with the participant’s ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
6. Any history of significant underlying psychiatric disorder, or a clinical assessment of suicidality based on the responses on the eCSSRS.
7. Any history of major depressive disorder with or without suicidal features, or anxiety disorders, that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient treatment.
8. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
9. Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome or sudden cardiac death. Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days of study drug administration.
10. 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. Specific medications listed in Section 6.9.1 may be allowed.
11. Participants who require concomitant medications known to be associated with a prolonged QTc.
12. Participants receiving any protocol-prohibited medication(s) and who are unwilling or unable to switch to an alternate medication).
13. The participant has ever received an investigational HIV vaccine (immunotherapeutic or immunomodulatory).
14. Exposure to an experimental drug or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of study intervention.
15. Participation in the study would result in donation of blood in excess of 500 mL within 56 days.
16. Exposure to more than four new investigational drugs or vaccines within 12 months prior to the first dosing day.
17. Current enrollment or past participation within the last 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) before signing of consent in any other clinical study involving an investigational study intervention or any other type of medical research.
18. Diagnostic Assessments: • Presence of HBsAg or HBcAb at screening • Positive Hepatitis C antibody test result at Screening • Positive Hepatitis C RNA test result at Screening. • Creatinine clearance (eGFR) of < 60 mL/min/1.73 m2 using CKD-EPI equation (2021)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Maximum Change from Baseline in logarithm in 10 base (log10) Plasma HIV-1 Ribonucleic Acid (RNA) Through Day 10

Secondary endpoints 14

1. Number of Participants with Adverse Events (AEs)
2. Number of Participants with AEs by severity
3. Number of Participants with AEs Leading to Study Treatment Discontinuation
4. Change from Baseline for Liver Panel Laboratory Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ASP) (International units per liter)
5. Change from Baseline for Liver Panel Laboratory Parameters: Total bilirubin, Direct bilirubin (Micromoles per liter [umol/L])
6. Change from Baseline for Liver Panel Laboratory Parameters: Albumin and Total Protein (Grams per liter [g/L])
7. Percentage of Participants with Maximum Toxicity Grade Increase Relative to Baseline in liver panel laboratory parameters: ALT, AST, total bilirubin, direct bilirubin, alkaline phosphatase, albumin and total protein
8. Maximum Observed Plasma Drug Concentration (Cmax) of VH4524184
9. Time to Maximum Observed Plasma Drugs Concentration (tmax) of VH4524184
10. Plasma Concentration of VH4524184 on Day 10
11. Correlation of VH4524184 PK Parameters with Maximum Plasma HIV-1 RNA change from baseline through Day 10
12. Number of Participants with Treatment-emergent Genotypic Resistance
13. Number of Participants with Treatment-emergent Phenotypic Resistance
14. Change From Baseline in Cluster of Differentiation 4 (CD4+) T-cell Counts at Day 10

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Viiv Healthcare UK Limited

Sponsor organisation

Viiv Healthcare UK Limited

Address

980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Viiv Healthcare UK Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Viiv Healthcare UK Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 10

Viiv Healthcare UK Limited

Sponsor organisation

Viiv Healthcare UK Limited

Address

79 New Oxford Street

City

London

Postcode

WC1A 1DG

Country

United Kingdom

Locations

2 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications