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)

HIV Infections Clinical Trial

— EMBRACE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05996471
• Other study ID #: 209639
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 17, 2023
• Est. completion date: May 15, 2026

Study information

• Verified date: March 2024
• Source: ViiV Healthcare
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 45
• Est. completion date: May 15, 2026
• Est. primary completion date: November 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion criteria Age

1. Participant must be 18 to 70 years of age inclusive, at the time of signing the informed consent. Type of Participant and Disease Characteristics

2. Must be on uninterrupted current 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 - ARV regimens prior to Screening include at least one NRTI plus:

• INI
• NNRTI
• Boosted PI (or atazanavir [ATV] unboosted)
• Excludes current use of cabotegravir or fostemsavir The addition, removal, or switch of a drug(s) that has been used to treat HIV based on antiretroviral properties of the drug constitutes a change in ART with the following

limited exceptions:

• Historical changes in formulations of ART drugs or booster drugs will not constitute a change in ART regimen if the data support similar exposures and efficacy, and the change must have been at least 3 months prior to Screening.
• Historical maternal perinatal use of an NRTI when given in addition to an ongoing HAART will not be considered a change in ART regimen.
• A change in dosing scheme of the same drug from twice daily to once daily will not be considered a change in ART regimen if data support similar exposures and efficacy.

3. 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;

4. Plasma HIV-1 RNA <50 c/mL at Screening;

5. Screening CD4+ T-cell count =350 cells/mm3:

Weight

6. Body weight >=50 kg to <=115 kg. Sex

7. Male and/or female Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies, assuring minimal contraception requirements noted below. All participants participating in the study should be counselled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g. male condom) and on the risk of HIV transmission to an uninfected partner.

1. Participants who are female at birth are eligible to participate if at least one of

the following conditions applies:

• Not pregnant or breastfeeding and at least one of the following conditions

applies:

• Is not a participant of childbearing potential (POCBP). OR
• Is a POCBP and using an acceptable contraceptive method during the intervention period (at a minimum until after the last dose of study intervention). The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
• A POCBP must have a negative highly sensitive (see Section 10.4) pregnancy test (urine or serum as required by local regulations) on Day 1, prior to the first dose of study intervention.
• If a urine test cannot be confirmed as negative (e.g., an 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.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a POCBP with an early undetected pregnancy. QTc 8. QTc Interval <450 msec. Phenotypic Sensitivity 9. Viral phenotypic sensitivity to VH3810109 based on IC90 of <=2 ug/mL and a Maximum Percent Inhibition >98% using the Monogram PhenoSense mAb Assay on sample obtained at a screening visit. Informed Consent 10. 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. Exclusion Criteria:

Medical conditions:

• 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
• Contraindications, as per the current Prescribing Information for cabotegravir.
• Previous hypersensitivity reaction to cabotegravir or
• Contraindicated co-administered drugs:
• Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin
• Antimycobacterials: Rifabutin, rifampin, rifapentine
• Glucocorticoid (systemic): Dexamethasone (more than a single-dose treatment)
• Herbal product: St John's wort (Hypericum perforatum)

Prior/Concomitant Therapy:

• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
• Previous exposure to cabotegravir.
• Treatment with any of the following agents within 60 days of screening:

-radiation therapy; -cytotoxic chemotherapeutic agents; -any systemic immune suppressant.

• Exposure to an experimental drug or experimental vaccine within either 28 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 medication.
• Current or anticipated need for chronic anti-coagulants.
• Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication. Prior/Concurrent Clinical Study Experience • Participant enrolled in a prior or concurrent clinical study that includes a drug intervention within the last 30 days. Diagnostic Assessments
• Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the participants inclusion in the study of an investigational compound.
• Any evidence of viral resistance based on the presence of any major cabotegravir resistance-associated mutation [IAS-USA, 2022] in any historic resistance test result.
• Any verified Grade 4 laboratory abnormality with the exception of Grade 4 triglycerides or lipid abnormalities. A single repeat test is allowed during the Screening period to verify a result.
• Alanine aminotransferase (ALT) .3 times the upper limit of normal (ULN)
• Creatinine clearance of <50 mL/min/1.73 m2 via using the refitted, race-neutral Chronic Kidney Disease Epidemiology Collaboration (CKD-EPIcr_R) method.
• PT .Grade 2 (.1.25 ULN). A single repeat test is allowed during the Screening period to verify a result. Other Exclusion Criteria
• To assess any potential impact on participant eligibility with regard to safety, the investigator must refer to the IB and supplements, approved product labels, and/or local prescribing information for detailed information regarding warnings, precautions, contraindications, AEs, drug interactions, and other significant data pertaining to the study drugs.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Biological:
• VH3810109
VH3810109 will be administered.

Drug:
• Cabotegravir
Cabotegravir will be administered.
• Standard of care (SOC)
Pre-baseline SOC antiretroviral therapy (ART) will be administered.

Biological:
• rHuPH20
rHuPH20 will be administered.

Locations

Country	Name	City	State
Puerto Rico	GSK Investigational Site	San Juan
Puerto Rico	GSK Investigational Site	San Juan
United States	GSK Investigational Site	Albuquerque	New Mexico
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Bakersfield	California
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Bronx	New York
United States	GSK Investigational Site	Bronx	New York
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Columbia	Missouri
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Decatur	Georgia
United States	GSK Investigational Site	El Paso	Texas
United States	GSK Investigational Site	Fort Lauderdale	Florida
United States	GSK Investigational Site	Fort Pierce	Florida
United States	GSK Investigational Site	Greensboro	North Carolina
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Manhasset	New York
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Milwaukee	Wisconsin
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	New Haven	Connecticut
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Newark	New Jersey
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Palm Springs	California
United States	GSK Investigational Site	Pensacola	Florida
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	Santa Fe	New Mexico
United States	GSK Investigational Site	Sarasota	Florida
United States	GSK Investigational Site	Southfield	Michigan
United States	GSK Investigational Site	Springfield	Massachusetts
United States	GSK Investigational Site	Vero Beach	Florida
United States	GSK Investigational Site	Washington	District of Columbia
United States	GSK Investigational Site	Washington	District of Columbia
United States	GSK Investigational Site	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
ViiV Healthcare

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

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