A Study to Investigate the Virologic Efficacy and Safety of VH3810109 + Cabotegravir Compared to Standard of Care (SOC) in Male and Female Adults Living With Human Immunodeficiency Virus (HIV)

Study Overview
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Brief Summary
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The study aims at evaluating the efficacy of VH3810109, dosed in accordance with the dosing schedule as either intravenous (IV) infusion or subcutaneous (SC) infusion with recombinant hyaluronidase (rHuPH20), in combination with cabotegravir (CAB) intramuscular (IM) dosed in accordance with the dosing schedule in virologically suppressed, Antiretroviral therapy (ART)-experienced adult participants living with HIV.

Official Title
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A Phase 2b Multicenter, Randomized, Open-Label Study Comparing the Efficacy, Safety, PK, and Tolerability of VH3810109, Administered Either Intravenously Or As A Subcutaneous Infusion With rHuPH20, in Combination With CAB LA to Standard of Care in Virologically Suppressed Adults Living With HIV

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: VH3810109
* Drug: Cabotegravir
* Drug: Standard of care (SOC)
* Biological: rHuPH20


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: •Participants must be on uninterrupted current regimen (either the initial or second Antiretroviral (ARV) regimen) for at least 6 months prior to Screening. Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability/safety, access to medications, or convenience/simplification, and must NOT have been done for treatment failure (HIV-1 RNA ≥200 c/mL). Acceptable stable (initial or second) ARV regimens prior to Screening include at least one Nucleoside reverse transcriptase inhibitor (NRTI) plus: Integrase inhibitor (INI) (either the initial or second combination ART (cART) regimen) Non-nucleoside reverse transcriptase inhibitors (NNRTI) (either the initial or second cART regimen) Boosted Protease Inhibitor (PI) (or atazanavir [ATV] unboosted) (must be either the initial cART regimen or one historical within class switch is permitted due to safety/tolerability) Excludes current use of cabotegravir or fostemsavir Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: one within the 6 to 12-month window, and one within 6 months prior to Screening Participants with plasma HIV-1 RNA <50 c/mL at Screening Screening CD4+ T-cell count ≥350 cells/cubic millimetre (mm^3) Body weight ≥ 50 kilograms (kg) to ≤115 kg QTc Interval <450 milliseconds (msec) Participants with viral phenotypic sensitivity to VH3810109 based on IC90 of ≤2 micrograms (μg)/millilitre (mL) and a Maximum Percent Inhibition >98% using the Monogram PhenoSense monoclonal antibody (mAb) Assay on sample obtained at a screening visit Participants capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol Participants female at birth should either not be of childbearing potential or using acceptable contraceptive method Exclusion Criteria: Participants who are pregnant, breastfeeding, plan to become pregnant or breastfeed during the study Participants having skin disease or disorder (i.e. infection, inflammation, dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy, urticaria) or tattoo overlying potential injection sites which may interfere with interpretation of injection site reactions or administration of VH3810109 or CAB Participant has a gluteal implant/enhancement (including fillers) overlying the gluteus area or any other area which may significantly interfere with interpretation of injection site reactions Participants with known history of cirrhosis with or without viral hepatitis co-infection Participants with ongoing or clinically relevant pancreatitis Untreated syphilis infection (positive rapid plasma reagin (RPR) at screening) without documentation of treatment. Participants who are at least 7 days post completed treatment are eligible if recruitment is open Prior receipt of licensed or investigational HIV monoclonal antibody Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease except cutaneous Kaposi's sarcoma not requiring systemic therapy. Historical or current CD4 cell counts less than 200 cells/mm^3 are not exclusionary History of sensitivity to any of the study medications or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation Any condition which, in the opinion of the investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs, cART or render the participant unable to take oral medication Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening Previous exposure to cabotegravir Participant enrolled in a prior or concurrent clinical study that includes a drug intervention within the last 30 days Participants with ongoing chronic hepatitis B virus infection Participants with hepatitis C co-infection Participants who in the investigator's judgment, pose a significant suicidality risk Participants with a positive coronavirus disease- 2019 (COVID-19) test at screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants Receiving VH3810109 Plus Cabotegravir<br> | Biological: VH3810109<br>* VH3810109 will be administered.<br>Drug: Cabotegravir<br>* Cabotegravir will be administered.<br>|
| Experimental: Participants Receiving VH3810109 Plus rHuPH20 Plus Cabotegravir<br> | Biological: VH3810109<br>* VH3810109 will be administered.<br>Drug: Cabotegravir<br>* Cabotegravir will be administered.<br>Biological: rHuPH20<br>* rHuPH20 will be administered.<br>|
| Active Comparator: Participants Receiving Standard of Care (SOC) Antiretroviral Therapy (ART)<br> | Drug: Standard of care (SOC)<br>* Pre-baseline SOC antiretroviral therapy (ART) will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Plasma HIV-1 Ribonucleic acid (RNA) Greater Than or Equal to (≥)50 Copies per Millilitre (c/mL) per Snapshot Algorithm at Month 6 |  | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Serious Adverse Events (SAEs), Deaths, and Adverse Events (AEs) Leading to Discontinuation of Investigational Product (IP) |  | Up to Month 24 | 
| Number of Participants with Grade 3-4 AEs |  | Up to Month 24 | 
| Number of Participants with Laboratory Abnormalities |  | Up to Month 24 | 
| Number of Participants with Grade 1-4 Injection Site Reactions |  | Up to Month 24 | 
| Number of Participants Meeting Confirmed Virologic Failure (CVF) Criteria Through Month 24 |  | Up to Month 24 | 
| Number of Participants with Plasma HIV-1 RNA ≥50 c/mL per Snapshot Algorithm Over Time |  | Up to Month 24 | 
| Number of Participants with Plasma HIV-1 RNA Less Than (<)50 c/mL per Snapshot Algorithm Over Time |  | Up to Month 24 | 
| Number of Participants with HIV Disease Progression |  | Up to Month 24 | 
| Serum Concentrations of VH3810109 |  | Up to Month 24 | 
| Plasma Concentrations of Cabotegravir |  | Up to Month 24 | 
| Absolute Value for Cluster of Differentiation 4 (CD4+) T-Cell Count |  | Up to Month 24 | 
| Change From Baseline in CD4+ T-Cell Count |  | Baseline (Day 1) and up to Month 24 | 
| Absolute Value for Cluster of Differentiation 8 (CD8+) T-Cell Count |  | Up to Month 24 | 
| Change From Baseline in CD8+ T-Cell Count |  | Baseline (Day 1) up to Month 24 | 
| Number of Participants with Anti-VH3810109 Antibodies |  | Up to Month 24 | 
| Number of Participants with Neutralizing Antibodies Against VH3810109 |  | Up to Month 24 | 
| Number of Participants with Treatment-emergent Genotypic Resistance |  | Up to Month 24 | 
| Number of Participants with Treatment-emergent Phenotypic Resistance |  | Up to Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, VH3810109, Cabotegravir, Standard of care, Long acting, Virologically Suppressed