A Study to Evaluate the Antiviral Effect, Safety and Tolerability of GSK3810109A in Viremic Human Immunodeficiency Virus (HIV)-1 Infected Adults

NCT ID: NCT04871113

Last Updated: 2024-10-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-22
• Study Completion Date: 2023-09-21

Brief Summary

This study is to evaluate antiviral activity, efficacy, safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of GSK3810109A in HIV-1 infected treatment naive adults. Participants will receive a single dose of GSK3810109A administered either intravenously (IV) or subcutaneously (SC). The study includes a screening phase, a randomized monotherapy phase and a standard of care follow-up phase.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1:GSK3810109A 40milligram(mg)/kilogram intravenously (IV)

Participants with human immunodeficiency viruses-1 (HIV-1) received GSK3810109A as a single intravenous (IV) infusion of 40 milligrams per kilogram (mg/kg) dose based on individual bodyweight on Day 1 in part 1.

Group Type: EXPERIMENTAL

GSK3810109A

Intervention Type: BIOLOGICAL

GSK3810109A available as sterile aqueous solution.

Part 1: GSK3810109A 280 mg IV

Participants with HIV-1 received GSK3810109A as a single IV infusion of 280 mg dose on Day 1 in part 1.

Group Type: EXPERIMENTAL

GSK3810109A

Intervention Type: BIOLOGICAL

GSK3810109A available as sterile aqueous solution.

Part 2: GSK3810109A 700 mg IV

Participants with HIV-1 received GSK3810109A as a single IV infusion of 700 mg dose on Day 1 in part 2. This included dose level determined based on the data of part 1.

Group Type: EXPERIMENTAL

GSK3810109A

Intervention Type: BIOLOGICAL

GSK3810109A available as sterile aqueous solution.

Part 2: GSK3810109A 70 mg IV

Participants with HIV-1 received GSK3810109A as a single IV infusion of 70 mg dose on Day 1 in part 2. This included dose level determined based on the data of part 1.

Group Type: EXPERIMENTAL

GSK3810109A

Intervention Type: BIOLOGICAL

GSK3810109A available as sterile aqueous solution.

Part 2: GSK3810109A 700 mg subcutaneously (SC)

Participants with HIV-1 received GSK3810109A as a subcutaneous (SC) injection of total 700 mg dose administered as three equally divided SC injections of 2.33 mL each (approximately 7 mL) in quick succession at same time on Day 1 in part 2. This included dose level determined based on the data of part 1.

Group Type: EXPERIMENTAL

GSK3810109A

Intervention Type: BIOLOGICAL

GSK3810109A available as sterile aqueous solution.

Standard of care (SOC) - GSK3810109A 40mg/kg IV

Participants who completed the monotherapy phase of treatment of GSK3810109A 40mg/kg IV entered SOC phase to receive dolutegravir + lamivudine regimen as a SOC treatment on SOC Day 1 if deemed appropriate by the investigator and consistent with local guidelines.

Group Type: EXPERIMENTAL

Dolutegravir+lamivudine SOC regimen

Intervention Type: BIOLOGICAL

Dolutegravir+lamivudine regimen administered in consistence with investigator input and local guidelines

SOC - GSK3810109A 280 mg IV

Participants who completed the monotherapy phase of treatment of GSK3810109A 280 mg IV entered SOC phase to receive dolutegravir + lamivudine regimen as a SOC treatment on SOC Day 1 if deemed appropriate by the investigator and consistent with local guidelines.

Group Type: EXPERIMENTAL

Dolutegravir+lamivudine SOC regimen

Intervention Type: BIOLOGICAL

Dolutegravir+lamivudine regimen administered in consistence with investigator input and local guidelines

SOC - GSK3810109A 700 mg IV

Participants who completed the monotherapy phase of treatment of GSK3810109A 700 mg IV entered SOC phase to receive dolutegravir + lamivudine regimen as a SOC treatment on SOC Day 1 if deemed appropriate by the investigator and consistent with local guidelines.

Group Type: EXPERIMENTAL

Dolutegravir+lamivudine SOC regimen

Intervention Type: BIOLOGICAL

Dolutegravir+lamivudine regimen administered in consistence with investigator input and local guidelines

SOC - GSK3810109A 70 mg IV

Participants who completed the monotherapy phase of treatment of GSK3810109A 70 mg IV entered SOC phase to receive dolutegravir + lamivudine regimen as a SOC treatment on SOC Day 1 if deemed appropriate by the investigator and consistent with local guidelines.

Group Type: EXPERIMENTAL

Dolutegravir+lamivudine SOC regimen

Intervention Type: BIOLOGICAL

Dolutegravir+lamivudine regimen administered in consistence with investigator input and local guidelines

SOC - GSK3810109A 700 mg SC

Participants who completed the monotherapy phase of treatment of GSK3810109A 700 mg SC entered SOC phase to receive dolutegravir + lamivudine regimen as a SOC treatment on SOC Day 1 if deemed appropriate by the investigator and consistent with local guidelines.

Group Type: EXPERIMENTAL

Dolutegravir+lamivudine SOC regimen

Intervention Type: BIOLOGICAL

Dolutegravir+lamivudine regimen administered in consistence with investigator input and local guidelines

Interventions

GSK3810109A

GSK3810109A available as sterile aqueous solution.

Intervention Type: BIOLOGICAL

Dolutegravir+lamivudine SOC regimen

Dolutegravir+lamivudine regimen administered in consistence with investigator input and local guidelines

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
• Participants must have HIV-1 infection within 45 days of the Screening Visit: Plasma HIV-1 RNA greater than or equal to (>=) 5000 copies/mL (c/mL).
• Confirmed screening CD4+ T-cell count >= 350 cells per cubic millimeter (cells/mm3).
• Antiretroviral naïve: No Antiretroviral therapy (ARTs) (in combination or monotherapy) received after the diagnosis of HIV-1 infection.
• Body weight >= 50 kg to less than or equal to (<=) 115 kg.
• 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. 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; a. 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 (example [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.
• Corrected QT interval (QTc) Interval <= 450 milliseconds (msec)
• Capable of giving signed informed consent.

Exclusion Criteria

• Participants with primary HIV infection, evidenced by acute retroviral syndrome (e.g., fever, malaise, fatigue, etc) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion.
• Participants who are pregnant, breastfeeding, plan to become pregnant or breastfeed during the study.
• The participant has an underlying skin disease or disorder (example i.e. infection, inflammation, dermatitis, eczema, drug rash, drug allergy, psoriasis, food allergy, urticaria) that would interfere with assessment of injection sites.
• Known history of cirrhosis with or without viral hepatitis co-infection.
• History of clinically relevant hepatitis within last 6 months.
• Evidence of Hepatitis B virus (HBV) infection based on the results of testing at screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antigen antibody (anti-HBs) and HBV Deoxyribonucleic acid (DNA) as follows: Participants positive for HBsAg are excluded; Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded. Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and negative for HBV DNA are not excluded.
• Participants with Hepatitis C co-infection.
• Untreated syphilis infection (positive rapid plasma reagin [RPR] at screening) without documentation of treatment. Participants who are one month post completed treatment are eligible if recruitment is open.

Rescreening is allowed after treatment.

• Prior receipt of licensed or investigational 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.
• Known or suspected moderate or severe hepatic impairment (Class C as determined by Child-Pugh Classification) coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Clinically significant cardiovascular disease, as defined by history/evidence of congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease at the discretion of the investigator.
• 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; other localized malignancies require agreement between the investigator and the study medical monitor for inclusion of the participant prior to randomization.
• 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.
• Participants with substance abuse disorders or social restraints that the investigator considers to be possible deterrents to successful completion of the study.
• Participants who in the investigator's judgment, pose a significant suicidality risk. Participants' history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk.
• 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, combination ART or render the participant unable to take oral medication.
• Participants with a positive Corona Virus Disease 2019 (COVID-19) test at Screening. Participants with known COVID-19 positive contacts within the past 14 days, or with symptoms suggestive of active COVID-19 (fever, cough, myalgias, shortness of breath, loss of taste or smell), should be excluded. Participants who remain symptom-free for at least 14 days after a COVID-19 exposure are allowed.
• Has received any HIV-1 immunotherapeutic vaccine or prophylactic vaccine.
• Treatment with any of the following agents within 28 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 IP.
• Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication.
• Participant enrolled in a prior or concurrent clinical study that includes a drug intervention within the last 30 days.
• Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the participant's inclusion in the study of an investigational compound.
• Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening period to verify a result.
• ALT >= 3 times the upper limit of normal (ULN).
• Creatinine clearance of <50 mL/minute/1.73 meter^2) via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method.
• The participant has a tattoo or other dermatological condition overlying potential injection sites which may interfere with interpretation of injection site reactions or administration of GSK3810109A.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ViiV Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

GSK Investigational Site

Long Beach, California, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Orlando, Florida, United States

GSK Investigational Site

Berkley, Michigan, United States

GSK Investigational Site

Manhasset, New York, United States

GSK Investigational Site

Dallas, Texas, United States

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Ciudad Autonoma de Bueno, , Argentina

GSK Investigational Site

Mar del Plata, , Argentina

GSK Investigational Site

Rosario, , Argentina

GSK Investigational Site

San Juan, , Argentina

GSK Investigational Site

Rio de Janeiro, , Brazil

GSK Investigational Site

São Paulo, , Brazil

GSK Investigational Site

Ottawa, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Regina, Saskatchewan, Canada

GSK Investigational Site

Mérida, , Mexico

GSK Investigational Site

Monterrey, , Mexico

GSK Investigational Site

Lima, , Peru

Countries

United States; Argentina; Brazil; Canada; Mexico; Peru

References

Leone P, Ferro A, Rolle CP, Lupo S, McGowan J, Klein M, Cahn P, Benson P, Griesel R, Warwick-Sanders M, Sanchez M, D'Agostino R, Bettacchi C, Schneider S, Wannamaker P, Dorey D, Wilches V, Gartland M, Brown K, Gandhi Y, Donatti C, Losos J. VH3810109 Efficacy, Safety, Pharmacokinetics, and Incidence of Anti-drug Antibodies in Adults With HIV-1 Naive to Antiretroviral Therapy: BANNER Study Results. J Infect Dis. 2025 Sep 2:jiaf450. doi: 10.1093/infdis/jiaf450. Online ahead of print.

Reference Type: DERIVED

PMID: 40892985 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

207959

Identifier Type: -

Identifier Source: org_study_id