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

NCT04871113 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 207959
• Study Type: interventional
• Target: 62
• Locations: 6 countries
• Sites: 24

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

Keywords

Antiretroviral-naïve; Broadly neutralizing antibody; GSK3810109A; HIV; N6LS

Outcome Measures

Primary Outcomes (5)

• Maximum Decline From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) Levels - Monotherapy Phase

  Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. Maximum decline from baseline in plasma HIV-1 RNA were measured in participants. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. End of Monotherapy Phase is defined as the timepoint when a participant had reached the monotherapy endpoint criteria or a maximum of 84 days follow-up, whichever occurred first.

  Baseline (Day 1) and up to Day 84 or end of Monotherapy Phase

• Number of Participants With Adverse Events (AEs) - Monotherapy Phase

  An adverse event (AE) is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. End of Monotherapy Phase is defined as the timepoint when a participant had reached the monotherapy endpoint criteria or a maximum of 84 days follow-up, whichever occurred first.

  Up to Day 84 or end of Monotherapy Phase

• Number of Participants With Worst-case Maximum Grade 2-4 Increase in Post-baseline Values of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Compared to the Baseline Values - Monotherapy Phase

  Blood samples were collected for the analysis of ALT and AST parameters. The parameters ALT and AST were graded using the Division of Acquired Immunodeficiency Syndrome (DAIDS) criteria Version 2.1 where grades were defined based on numeric criteria as follows Grade 0: participants with missing baseline values; Grade 1: Mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates greater severity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data of number of participants with 2-4 grade increase at worst-case post-baseline (maximum grade increase post-baseline) is presented. End of Monotherapy Phase is defined as the timepoint when a participant had reached the monotherapy endpoint criteria or a maximum of 84 days follow-up, whichever occurred first.

  Baseline (Day 1) and up to Day 84 or end of Monotherapy Phase

• Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Findings - Monotherapy Phase

  A 12-lead ECG were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using Fridericia's formula (QTcF) intervals. ECG findings were categorized as normal, abnormal clinically significant (CS) and abnormal not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with abnormal (CS and NCS) ECG findings are presented. End of Monotherapy Phase is defined as the timepoint when a participant had reached the monotherapy endpoint criteria or a maximum of 84 days follow-up, whichever occurred first.

  Up to Day 84 or end of Monotherapy Phase

• Number of Participants With Grade 2-4 Injection Site Reactions (ISR) - Monotherapy Phase

  Number of participants with grade 2-4 injection site reactions are presented. The ISR were graded using the Division of Acquired immunodeficiency syndrome (DAIDS) criteria Version 2.1 where grades were defined based on numeric criteria as follows Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severe condition. End of Monotherapy Phase is defined as the timepoint when a participant had reached the monotherapy endpoint criteria or a maximum of 84 days follow-up, whichever occurred first.

  Up to Day 84 or end of Monotherapy Phase

Secondary Outcomes (13)

• Area Under the Plasma Concentration-time Curve From Time Zero to the Day 14 (AUC [0-14]) of GSK3810109A - Monotherapy Phase

  Pre-dose (Day 1), 3 and 24 hours post-dose on day 1, days 3, 6, 9, 11, and 14

• Maximum Observed Plasma Concentration (Cmax) of GSK3810109A - Monotherapy Phase

  Pre-dose (Day 1), 3 and 24 hours post-dose on day 1, days 3, 6, 9, 11, and 14

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of GSK3810109A - Monotherapy Phase

  Pre-dose (Day 1), 3 and 24 hours post-dose on day 1, days 3, 6, 9, 11, and 14

• Plasma Concentration at Day 14 (C14) of GSK3810109A - Monotherapy Phase

  At Day 14

• Change From Baseline in Log10 Plasma HIV-1 RNA Relative to Cmax - Monotherapy Phase

  Baseline (Day 1) and up to Day 84 or end of Monotherapy Phase

Study Arms (10)

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

EXPERIMENTAL

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.

Biological: GSK3810109A

Part 1: GSK3810109A 280 mg IV

EXPERIMENTAL

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

Biological: GSK3810109A

Part 2: GSK3810109A 700 mg IV

EXPERIMENTAL

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.

Biological: GSK3810109A

Part 2: GSK3810109A 70 mg IV

EXPERIMENTAL

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.

Biological: GSK3810109A

Part 2: GSK3810109A 700 mg subcutaneously (SC)

EXPERIMENTAL

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.

Biological: GSK3810109A

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

EXPERIMENTAL

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.

Biological: Dolutegravir+lamivudine SOC regimen

SOC - GSK3810109A 280 mg IV

EXPERIMENTAL

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.

Biological: Dolutegravir+lamivudine SOC regimen

SOC - GSK3810109A 700 mg IV

EXPERIMENTAL

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.

Biological: Dolutegravir+lamivudine SOC regimen

SOC - GSK3810109A 70 mg IV

EXPERIMENTAL

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.

Biological: Dolutegravir+lamivudine SOC regimen

SOC - GSK3810109A 700 mg SC

EXPERIMENTAL

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.

Biological: Dolutegravir+lamivudine SOC regimen

Interventions

GSK3810109A BIOLOGICAL

GSK3810109A available as sterile aqueous solution.

Part 1: GSK3810109A 280 mg IV; Part 1:GSK3810109A 40milligram(mg)/kilogram intravenously (IV); Part 2: GSK3810109A 70 mg IV; Part 2: GSK3810109A 700 mg IV; Part 2: GSK3810109A 700 mg subcutaneously (SC)

Dolutegravir+lamivudine SOC regimen BIOLOGICAL

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

SOC - GSK3810109A 280 mg IV; SOC - GSK3810109A 70 mg IV; SOC - GSK3810109A 700 mg IV; SOC - GSK3810109A 700 mg SC; Standard of care (SOC) - GSK3810109A 40mg/kg IV

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (24)

GSK Investigational Site

Long Beach, California, 90813, United States

Location

GSK Investigational Site

Los Angeles, California, 90027, United States

Location

GSK Investigational Site

Los Angeles, California, 90036, United States

Location

GSK Investigational Site

Orlando, Florida, 32803, United States

Location

GSK Investigational Site

Berkley, Michigan, 48072, United States

Location

GSK Investigational Site

Manhasset, New York, 11030, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

Buenos Aires, 1023, Argentina

Location

GSK Investigational Site

Buenos Aires, C1181ACH, Argentina

Location

GSK Investigational Site

Buenos Aires, C1202ABB, Argentina

Location

GSK Investigational Site

Buenos Aires, C1425AGC, Argentina

Location

GSK Investigational Site

Ciudad Autonoma de Bueno, C1405CKC, Argentina

Location

GSK Investigational Site

Mar del Plata, 7600, Argentina

Location

GSK Investigational Site

Rosario, S2000PBJ, Argentina

Location

GSK Investigational Site

San Juan, 5400, Argentina

Location

GSK Investigational Site

Rio de Janeiro, 21045-900, Brazil

Location

GSK Investigational Site

São Paulo, 05403-010, Brazil

Location

GSK Investigational Site

Ottawa, Ontario, K1H 8L6, Canada

Location

GSK Investigational Site

Toronto, Ontario, M5G 2N2, Canada

Location

GSK Investigational Site

Montreal, Quebec, H4A 3J1, Canada

Location

GSK Investigational Site

Regina, Saskatchewan, S4P 0W5, Canada

Location

GSK Investigational Site

Mérida, 97000, Mexico

Location

GSK Investigational Site

Monterrey, 66278, Mexico

Location

GSK Investigational Site

Lima, Lima 4, Peru

Location

Related Publications (1)

• Leone PA, 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 Antidrug Antibodies in Adults With HIV-1 Naive to Antiretroviral Therapy: BANNER Study Results. J Infect Dis. 2025 Dec 20;232(6):e1022-e1032. doi: 10.1093/infdis/jiaf450.

  PMID: 40892985 DERIVED

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The is a sequential treatment, two-part study which will include a screening phase, a randomized monotherapy phase and a standard of care follow-up phase.

Study Record Dates

• First Submitted: April 28, 2021
• First Posted: May 4, 2021
• Study Start: June 22, 2021
• Primary Completion: October 27, 2022
• Study Completion: September 21, 2023
• Last Updated: October 15, 2024
• Results First Posted: November 18, 2023

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.

Locations

PE (1); ME (2); US (7); AR (8); BR (2); CA (4)