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

Sponsor

ViiV Healthcare (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04871113

Collaborator

(none)

Enrollment

Locations

Arms

28.6

Anticipated Duration (Months)

1.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Biological: GSK3810109A	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

44 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

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.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.

Masking:

None (Open Label)

Masking Description:

This is an open-label study

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 22, 2021

Anticipated Primary Completion Date :

Dec 22, 2022

Anticipated Study Completion Date :

Nov 9, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: Participants receiving GSK3810109A 40 mg/kg (Cohort 1) Participants will be administered GSK3810109A as a single IV infusion of 40 mg/kg dose in Part 1.	Biological: GSK3810109A GSK3810109A will be available as sterile aqueous solution.
Experimental: Part 1: Participants receiving GSK3810109A 280 mg (Cohort 2) Participants will be administered GSK3810109A as a single IV infusion of 280 mg dose in Part 1.	Biological: GSK3810109A GSK3810109A will be available as sterile aqueous solution.
Experimental: Part 2: Participants receiving GSK3810109A (Cohort 3) Participants will be administered GSK3810109A as a single IV infusion or SC injection and will include dose level determined based on the data of Part 1.	Biological: GSK3810109A GSK3810109A will be available as sterile aqueous solution.
Experimental: Part 2: Participants receiving GSK3810109A (Cohort 4) Participants will be administered GSK3810109A as a single IV infusion or SC injection and will include dose level determined based on the data of Part 1	Biological: GSK3810109A GSK3810109A will be available as sterile aqueous solution.
Experimental: Part 2: Participants receiving GSK3810109A (Cohort 5) Participants will be administered GSK3810109A as a single IV infusion or SC injection and will include dose level determined based on the data of Part 1.	Biological: GSK3810109A GSK3810109A will be available as sterile aqueous solution.

Outcome Measures

Primary Outcome Measures

Maximum change from Baseline in plasma HIV-1 ribonucleic acid (RNA) levels (copies/milliliter) [Baseline and up to Day 84]
Number of participants with adverse events (AEs) and serious adverse events (SAEs) [Up to Week 60]
Number of participants with Grade 2-4 alanine aminotransferase (ALT) and aspartate aminotransferase (AST) abnormality [Up to Week 60]
Number of participants with treatment-emergent abnormal electrocardiogram (ECG) findings [Up to Day 84]
Number of participants with Grade 2-4 injection site reactions (ISR) [Up to Day 84]

Secondary Outcome Measures

Area under the concentration-time curve from time 0 to the last quantifiable concentration (AUC [0-t]) of GSK3810109A [Up to Week 60]
Maximum observed concentration (Cmax) of GSK3810109A [Up to Week 60]
Time to reach maximum observed plasma concentration (Tmax) of GSK3810109A [Up to Week 60]
Plasma concentration of GSK3810109A [Up to Week 60]
Change from Baseline in Plasma HIV-1 RNA in relation to Cmax [Baseline and up to Week 60]
Change from Baseline in Plasma HIV-1 RNA in relation to AUC [Baseline and up to Week 60]
Change from Baseline in cluster of differentiation 4 plus (CD4+) T cell counts (cells per cubic millimeters) [Baseline and up to Week 60]
Absolute values of CD4+ T cell counts [Up to Week 60]
Number of participants with positive anti-drug antibodies (ADAs) against GSK3810109A [Up to Week 60]
Titers of ADAs against GSK3810109A [Up to Week 60]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35294
2	GSK Investigational Site	Long Beach	California	United States	90813
3	GSK Investigational Site	Los Angeles	California	United States	90027
4	GSK Investigational Site	Los Angeles	California	United States	90036
5	GSK Investigational Site	Orlando	Florida	United States	32803
6	GSK Investigational Site	Tampa	Florida	United States	33606
7	GSK Investigational Site	Indianapolis	Indiana	United States	46202
8	GSK Investigational Site	Berkley	Michigan	United States	48072
9	GSK Investigational Site	Manhasset	New York	United States	11030
10	GSK Investigational Site	Durham	North Carolina	United States	27710
11	GSK Investigational Site	Charleston	South Carolina	United States	29425
12	GSK Investigational Site	Dallas	Texas	United States	75246
13	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1181ACH
14	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1425AGC
15	GSK Investigational Site	Ciudad Autónoma de Buenos Aires	Buenos Aires	Argentina	C1405CKC
16	GSK Investigational Site	Ciudad de Buenos Aires	Buenos Aires	Argentina	C1202ABB
17	GSK Investigational Site	Mar del Plata	Buenos Aires	Argentina	7600
18	GSK Investigational Site	Rosario	Santa Fe	Argentina	S2000PBJ
19	GSK Investigational Site	Buenos Aires		Argentina	1023
20	GSK Investigational Site	San Juan		Argentina	5400
21	GSK Investigational Site	Rio de Janeiro		Brazil	21045-900
22	GSK Investigational Site	São Paulo		Brazil	05403-010
23	GSK Investigational Site	Ottawa	Ontario	Canada	K1H 8L6
24	GSK Investigational Site	Toronto	Ontario	Canada	M5G 2N2
25	GSK Investigational Site	Montreal	Quebec	Canada	H2L 4E9
26	GSK Investigational Site	Montreal	Quebec	Canada	H4A 3J1
27	GSK Investigational Site	Regina	Saskatchewan	Canada	S4P 0W5
28	GSK Investigational Site	Monterrey	Nuevo León	Mexico	66278
29	GSK Investigational Site	Merida		Mexico	97000