EMBRACE: 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)

Sponsor

ViiV Healthcare (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05996471

Collaborator

(none)

150

Enrollment

Locations

Arms

32.2

Anticipated Duration (Months)

3.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Biological: VH3810109 Drug: Cabotegravir Drug: Standard of care (SOC) Biological: rHuPH20	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Aug 10, 2023

Anticipated Primary Completion Date :

Oct 23, 2024

Anticipated Study Completion Date :

Apr 17, 2026

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Participants Receiving VH3810109 Plus Cabotegravir

Biological: VH3810109

VH3810109 will be administered.

Drug: Cabotegravir

Cabotegravir will be administered.

Experimental: Participants Receiving VH3810109 Plus rHuPH20 Plus Cabotegravir

Biological: VH3810109

VH3810109 will be administered.

Drug: Cabotegravir

Cabotegravir will be administered.

Biological: rHuPH20

rHuPH20 will be administered.

Active Comparator: Participants Receiving Standard of Care (SOC) Antiretroviral Therapy (ART)

Drug: Standard of care (SOC)

Pre-baseline SOC antiretroviral therapy (ART) will be administered.

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35294
2	GSK Investigational Site	Bakersfield	California	United States	93301
3	GSK Investigational Site	Los Angeles	California	United States	90027
4	GSK Investigational Site	Palm Springs	California	United States	92262
5	GSK Investigational Site	Sacramento	California	United States	95825
6	GSK Investigational Site	San Francisco	California	United States	94110
7	GSK Investigational Site	New Haven	Connecticut	United States	06510
8	GSK Investigational Site	Washington	District of Columbia	United States	20007
9	GSK Investigational Site	Washington	District of Columbia	United States	20037
10	GSK Investigational Site	Fort Lauderdale	Florida	United States	33308
11	GSK Investigational Site	Fort Pierce	Florida	United States	34982
12	GSK Investigational Site	Miami	Florida	United States	33133
13	GSK Investigational Site	Orlando	Florida	United States	32803
14	GSK Investigational Site	Pensacola	Florida	United States	32504
15	GSK Investigational Site	Sarasota	Florida	United States	34237
16	GSK Investigational Site	Vero Beach	Florida	United States	32960
17	GSK Investigational Site	West Palm Beach	Florida	United States	33401
18	GSK Investigational Site	Decatur	Georgia	United States	30033
19	GSK Investigational Site	Boston	Massachusetts	United States	02115
20	GSK Investigational Site	Springfield	Massachusetts	United States	01105
21	GSK Investigational Site	Southfield	Michigan	United States	48075
22	GSK Investigational Site	Columbia	Missouri	United States	65212
23	GSK Investigational Site	Newark	New Jersey	United States	07102
24	GSK Investigational Site	Albuquerque	New Mexico	United States	87109
25	GSK Investigational Site	Santa Fe	New Mexico	United States	87505
26	GSK Investigational Site	Bronx	New York	United States	10461
27	GSK Investigational Site	Bronx	New York	United States	10467
28	GSK Investigational Site	Manhasset	New York	United States	11030
29	GSK Investigational Site	New York	New York	United States	10029
30	GSK Investigational Site	New York	New York	United States	10032
31	GSK Investigational Site	Chapel Hill	North Carolina	United States	27599
32	GSK Investigational Site	Greensboro	North Carolina	United States	27401-1209
33	GSK Investigational Site	Cincinnati	Ohio	United States	45267
34	GSK Investigational Site	Portland	Oregon	United States	97239
35	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19104
36	GSK Investigational Site	Nashville	Tennessee	United States	37208
37	GSK Investigational Site	Austin	Texas	United States	78705
38	GSK Investigational Site	Dallas	Texas	United States	75246
39	GSK Investigational Site	El Paso	Texas	United States	79902
40	GSK Investigational Site	Houston	Texas	United States	77098
41	GSK Investigational Site	Milwaukee	Wisconsin	United States	53226
42	GSK Investigational Site	San Juan		Puerto Rico	00909
43	GSK Investigational Site	San Juan		Puerto Rico	909