Clinical trial NCT05996471: 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)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: HIV Infections
Keywords: VH3810109
Cabotegravir
Standard of care
HIV
Long acting
Virologically Suppressed
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2023-08-18
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

VH3810109 plus rHuPH20 plus Cabotegravir arm of the study has been discontinued based on preliminary results.


Eligibility criteria: 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 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 m\^2 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.

Primary outcomes:
measure: 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
timeFrame: Month 6
Secondary outcomes:
measure: Number of Participants with Serious Adverse Events (SAEs), Deaths, and Adverse Events (AEs) Leading to Discontinuation of Investigational Product (IP)
timeFrame: Up to Month 24
measure: Number of Participants with Grade 3-4 AEs
timeFrame: Up to Month 24
measure: Number of Participants with Grade 3-4 Laboratory Abnormalities
timeFrame: Up to Month 24
measure: Number of Participants with Grade 1-4 Injection/infusion Site Reactions
timeFrame: Up to Month 24
measure: Number of Participants Meeting Confirmed Virologic Failure (CVF) Criteria Through Month 24
timeFrame: Up to Month 24
measure: Number of Participants with Plasma HIV-1 RNA ≥50 c/mL per Snapshot Algorithm Over Time
timeFrame: Up to Month 24
measure: Number of Participants with Plasma HIV-1 RNA Less Than (<)50 c/mL per Snapshot Algorithm Over Time
timeFrame: Up to Month 24
measure: Number of Participants with HIV Disease Progression
timeFrame: Up to Month 24
measure: Serum Concentrations of VH3810109
timeFrame: Up to Month 24
measure: Plasma Concentrations of Cabotegravir
timeFrame: Up to Month 24
measure: Absolute Value for Cluster of Differentiation 4 (CD4+) T-Cell Count
timeFrame: Up to Month 24
measure: Change From Baseline in CD4+ T-Cell Count
timeFrame: Baseline (Day 1) and up to Month 24
measure: Absolute Value for Cluster of Differentiation 8 (CD8+) T-Cell Count
timeFrame: Up to Month 24
measure: Change From Baseline in CD8+ T-Cell Count
timeFrame: Baseline (Day 1) up to Month 24
measure: Number of Participants with Anti-VH3810109 Antibodies
timeFrame: Up to Month 24
measure: Number of Participants with Neutralizing Antibodies Against VH3810109
timeFrame: Up to Month 24
measure: Number of Participants with Treatment-emergent Genotypic Resistance
timeFrame: Up to Month 24
measure: Number of Participants with Treatment-emergent Phenotypic Resistance
timeFrame: Up to Month 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Bakersfield
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Palm Springs
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: New Haven
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: GSK Investigational Site
state: Florida
city: Fort Pierce
country: United States
facility: GSK Investigational Site
state: Florida
city: Fort Pierce
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Pensacola
country: United States
facility: GSK Investigational Site
state: Florida
city: Sarasota
country: United States
facility: GSK Investigational Site
state: Florida
city: Vero Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Decatur
country: United States
facility: GSK Investigational Site
state: Georgia
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Springfield
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Southfield
country: United States
facility: GSK Investigational Site
state: Michigan
city: Columbia
country: United States
facility: GSK Investigational Site
state: Missouri
city: Newark
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Santa Fe
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Bronx
country: United States
facility: GSK Investigational Site
state: New York
city: Manhasset
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Greensboro
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: El Paso
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Watertown
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
Study officials:
References: