Clinical trial NCT04871113: A Study to Evaluate the Antiviral Effect, Safety and Tolerability of GSK3810109A in Viremic Human Immunodeficiency Virus (HIV)-1 Infected Adults
Official title: A Phase 2a Multicentre, Randomized, Open-Label, Two-Part Adaptive Design Study to Evaluate the Antiviral Effect, Safety and Tolerability of GSK3810109A, an HIV-1 Specific Broadly Neutralizing Human Monoclonal Antibody in Antiretroviral-naïve HIV-1-Infected Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Antiretroviral-naïve
Broadly neutralizing antibody
GSK3810109A
HIV
N6LS
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2021-05-04
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Maximum Decline From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) Levels - Monotherapy Phase
timeFrame: Baseline (Day 1) and up to Day 84 or end of Monotherapy Phase
measure: Number of Participants With Adverse Events (AEs) - Monotherapy Phase
timeFrame: Up to Day 84 or end of Monotherapy Phase
measure: 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
timeFrame: Baseline (Day 1) and up to Day 84 or end of Monotherapy Phase
measure: Number of Participants With Treatment-emergent Abnormal Electrocardiogram (ECG) Findings - Monotherapy Phase
timeFrame: Up to Day 84 or end of Monotherapy Phase
measure: Number of Participants With Grade 2-4 Injection Site Reactions (ISR) - Monotherapy Phase
timeFrame: Up to Day 84 or end of Monotherapy Phase
Secondary outcomes:
measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Day 14 (AUC [0-14]) of GSK3810109A - Monotherapy Phase
timeFrame: Pre-dose (Day 1), 3 and 24 hours post-dose on day 1, days 3, 6, 9, 11, and 14
measure: Maximum Observed Plasma Concentration (Cmax) of GSK3810109A - Monotherapy Phase
timeFrame: Pre-dose (Day 1), 3 and 24 hours post-dose on day 1, days 3, 6, 9, 11, and 14
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of GSK3810109A - Monotherapy Phase
timeFrame: Pre-dose (Day 1), 3 and 24 hours post-dose on day 1, days 3, 6, 9, 11, and 14
measure: Plasma Concentration at Day 14 (C14) of GSK3810109A - Monotherapy Phase
timeFrame: At Day 14
measure: Change From Baseline in Log10 Plasma HIV-1 RNA Relative to Cmax - Monotherapy Phase
timeFrame: Baseline (Day 1) and up to Day 84 or end of Monotherapy Phase
measure: Absolute Values of Cluster of Differentiation 4 Plus (CD4+) and CD8+ T Cell Counts - Monotherapy Phase
timeFrame: From Day 1 (Baseline) and up to Day 84 or end of Monotherapy Phase
measure: Absolute Values of CD4+ and CD8+ T Cell Counts - SOC Phase
timeFrame: Up to Week 48 (SOC Phase)
measure: Change From Baseline in CD4+ and CD8+ T Cell Counts - Monotherapy Phase
timeFrame: Up to Day 84 or end of Monotherapy Phase (compared with baseline [Day 1])
measure: Change From Baseline in CD4+ and CD8+ T Cell Counts - SOC Phase
timeFrame: Up to Week 48 (SOC Phase)
measure: Number of Participants With Positive Anti-drug Antibodies (ADAs) Against GSK3810109A - Monotherapy Phase
timeFrame: At Day 1 and Day 84 or end of Monotherapy Phase
measure: Number of Participants With Positive ADAs Against GSK3810109A - SOC Phase
timeFrame: At Week 48 (SOC Phase)
measure: Titers of Positive ADAs Against GSK3810109A - Monotherapy Phase
timeFrame: At Day 84 or end of Monotherapy Phase
measure: Titers of Positive ADAs Against GSK3810109A - SOC Phase
timeFrame: At Week 48 (SOC Phase)
Other outcomes:
Locations:
city: Long Beach
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: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Berkley
country: United States
facility: GSK Investigational Site
state: Michigan
city: Manhasset
country: United States
facility: GSK Investigational Site
state: New York
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma De Bueno
country: Argentina
facility: GSK Investigational Site
city: Mar del Plata
country: Argentina
facility: GSK Investigational Site
city: Rosario
country: Argentina
facility: GSK Investigational Site
city: San Juan
country: Argentina
facility: GSK Investigational Site
city: Rio de Janeiro
country: Brazil
facility: GSK Investigational Site
city: SAo Paulo
country: Brazil
facility: GSK Investigational Site
city: Ottawa
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Regina
country: Canada
facility: GSK Investigational Site
state: Saskatchewan
city: Merida
country: Mexico
facility: GSK Investigational Site
city: Monterrey
country: Mexico
facility: GSK Investigational Site
city: Lima
country: Peru
facility: GSK Investigational Site
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: