Evaluation of the Safety, Tolerability and Pharmacokinetics (PK) of GSK3732394 First-Time-in-Human (FTIH) Study

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK3732394 in Healthy Participants

This is a phase 1, 2-part, double-blind (sponsor-unblinded), randomized, placebo-controlled, FTIH study, that includes both single-ascending and multiple-ascending dose phase to assess the safety, tolerability, and pharmacokinetic (PK)/pharmacodynamic (PD) attributes of GSK3732394 in healthy subjects. The data gathered in this study will further enable clinical development of GSK3732394 in HIV-infected subjects. Approximately 72 healthy subjects will be randomized in the FTIH study. Part 1 will be the single ascending dose (SAD) phase and Part 2 will be the multiple ascending dose (MAD) phase. Each subject in the SAD cohort will receive a single dose of blinded GSK3732394 or blinded placebo (PBO) in 6:2 ratio. Part 1 will consist of five ascending single-dose cohorts with an additional expansion cohort included as needed. Part 2 will consist of up to three ascending repeat-dose cohorts (MAD Cohorts 1, 2, and 3), randomized to four weekly doses of blinded GSK3732394 or blinded PBO in 6:2 ratio to be administered on Days 1, 8, 15, and 22.

Study Overview

• Status: Terminated
• Conditions: HIV Infections
• Intervention / Treatment: Drug: GSK3732394; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
• Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
• Subjects who are able to understand and comply with protocol requirements and timetables, instructions, and protocol-stated restrictions
• Body mass index within the range 19 to 30 kilogram per meter square (kg/m2) inclusive, in addition to a weight range of 50kg to 100kg.
• Male and female healthy volunteers.
• All male subjects must agree to use contraception during the treatment period and for at least 100 days after the last dose of study treatment and refrain from donating sperm during this period.
• A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies; Not a woman of childbearing potential (WOCBP), A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 28 days prior to first dose, and 40 days after, the last dose of study treatment.
• Capable of giving signed informed consent.
• A signed and dated written informed consent must be completed prior to the subject's entry into the study.

Exclusion Criteria:

• Subject has a history or presence of cardiovascular, dermatological, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
• Subject has abnormal blood pressure (as determined by the investigator).
• Subject had symptomatic herpes zoster within 3 months prior to screening.
• Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, TB testing that includes a positive tuberculin skin test [TST]; defined as a skin induration greater than 5 millimeter [mm] at 48 to 72 hours,and regardless of Bacillus Calmette-Guerin [BCG] or other vaccination history) or a positive (not indeterminate) QuantiFERON-TB Gold test.
• Subjects with lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
• Subjects who had breast cancer within the past 10 years.
• Subjects who had history of severe injection site reaction (i.e., required emergency care or hospitalization) following any prior injection, including reaction to vaccines.
• Subjects with history of clinically significant allergy or prior hypersensitivity including those with a documented yeast allergy.
• Subjects with history of, or current concern for, a chronic immune deficiency disorder including, but not limited to: diabetes, sickle cell anemia, and malnutrition.
• Subjects having alanine transaminase (ALT) greater than 1.1 x upper limit of normal (ULN).
• Subjects with Hemoglobin levels below the normal range.
• Subjects with Platelet count <130,000 per cubic millimeters.
• Subjects with Creatinine clearance (CrCL) <90 milliliters per minute.
• Subjects with bilirubin greater than 1.1xULN (isolated bilirubin greater than 1.1xULN is acceptable if bilirubin is fractionated and direct bilirubin greater than 35%).
• Subjects who has current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Subjects having Fridericia QT correction formula (QTcF) greater than 450 milliseconds (msec).
• Subjects who had intended use of over-the-counter or prescription medication within 7 days prior to dosing.
• Subjects who had live vaccine(s) within 1 month prior to screening, or plans to receive such vaccines during the study.
• Subjects who had treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing.
• Subjects who had exposure to immune-modulating medications (including corticosteroids) within 30-days of Screening.
• Subjects whose participation in the study would result in loss of blood or blood products in excess of 500 (milliliter) mL within 56 days.
• Subjects who had Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Subjects with current enrollment or past participation within the last 30 days before signing of consent in this or any other clinical study involving an investigational study intervention or any other type of medical research.
• Absolute CD4+ T-cell count and CD4 percent (CD4%) outside of the normal range for the reference laboratory (to be confirmed at baseline, e.g., Day -1).
• Subjects who had presence of Hepatitis B surface antigen (HBsAg) at screening.
• Subjects with positive Hepatitis C antibody test result at screening.
• Subjects with positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention.
• Subjects with positive pre-study drug/alcohol screen.
• Subjects with positive human immunodeficiency virus (HIV) antibody test.
• Subjects with history of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 14 units. One unit is equivalent to 8 grams (g) of alcohol: a half pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• Subjects with urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6 months prior to screening.
• Subjects who has sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1,Cohort 1:Subjects receiving blinded GSK3732394 10mg/PBO; GSK3732394 10 milligram (mg) or PBO will be administered by subcutaneous (SC) injection to the subjects.	Drug: GSK3732394; It is composed of an anti-CD4 adnectin, an anti-N17 adnectin, and a peptide inhibitor. This will be provided as a solution for injection in 1 (milliliter) mL glass vials with the unit dose strength of 100 mg/mL; Drug: Placebo; Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.
Experimental: Part 1,Cohort 2:Subjects receiving blinded GSK3732394 40mg/PBO; GSK3732394 40 mg or PBO will be administered by SC injection to the subjects. This is projected dose, dose will be based on PK/PD results from preceding dosing cohorts.	Drug: GSK3732394; It is composed of an anti-CD4 adnectin, an anti-N17 adnectin, and a peptide inhibitor. This will be provided as a solution for injection in 1 (milliliter) mL glass vials with the unit dose strength of 100 mg/mL; Drug: Placebo; Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.
Experimental: Part1,Cohort 3:Subjects receiving blinded GSK3732394 130mg/PBO; GSK3732394 130 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 3 will be based on PK/PD results from preceding dosing cohorts.	Drug: GSK3732394; It is composed of an anti-CD4 adnectin, an anti-N17 adnectin, and a peptide inhibitor. This will be provided as a solution for injection in 1 (milliliter) mL glass vials with the unit dose strength of 100 mg/mL
Experimental: Part1,Cohort 4:Subjects receiving blinded GSK3732394 350mg/PBO; GSK3732394 350 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 4 will be based on PK/PD results from preceding dosing cohorts.	Drug: GSK3732394; It is composed of an anti-CD4 adnectin, an anti-N17 adnectin, and a peptide inhibitor. This will be provided as a solution for injection in 1 (milliliter) mL glass vials with the unit dose strength of 100 mg/mL; Drug: Placebo; Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.
Experimental: Part1,Cohort5: Subjects receiving blinded GSK3732394 600mg/PBO; GSK3732394 600 mg or PBO will be administered by SC injection to the subjects. This is a projected dose. The dose administered in Part 1, Cohort 5 will be based on PK/PD results from preceding dosing cohorts.	Drug: GSK3732394; It is composed of an anti-CD4 adnectin, an anti-N17 adnectin, and a peptide inhibitor. This will be provided as a solution for injection in 1 (milliliter) mL glass vials with the unit dose strength of 100 mg/mL; Drug: Placebo; Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.
Experimental: Part1,Cohort6: Subjects receiving blinded GSK3732394 800mg/PBO; GSK3732394 800 mg or PBO will be administered by SC injection to the subjects. This is a projected dose and will be given if necessary. The dose administered in Part 1, Cohort 6 (if necessary) will be based on PK/PD results from preceding dosing cohorts.	Drug: GSK3732394; It is composed of an anti-CD4 adnectin, an anti-N17 adnectin, and a peptide inhibitor. This will be provided as a solution for injection in 1 (milliliter) mL glass vials with the unit dose strength of 100 mg/mL; Drug: Placebo; Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.
Experimental: Part2,Cohort1: Subjects receiving blinded GSK3732394 130mg/PBO; GSK3732394 130 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The dose administered in Part 2, Cohort 1 will be based on PK/PD results from preceding dosing cohorts.	Drug: GSK3732394; It is composed of an anti-CD4 adnectin, an anti-N17 adnectin, and a peptide inhibitor. This will be provided as a solution for injection in 1 (milliliter) mL glass vials with the unit dose strength of 100 mg/mL; Drug: Placebo; Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.
Experimental: Part2,Cohort2: Subjects receiving blinded GSK3732394 400mg/PBO; GSK3732394 400 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The administered dose in Part 2, Cohort 2 will be based on PK/PD results from preceding dosing cohorts.	Drug: GSK3732394; It is composed of an anti-CD4 adnectin, an anti-N17 adnectin, and a peptide inhibitor. This will be provided as a solution for injection in 1 (milliliter) mL glass vials with the unit dose strength of 100 mg/mL; Drug: Placebo; Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.
Experimental: Part2,Cohort3: Subjects receiving blinded GSK3732394 600mg/PBO; GSK3732394 600 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. This is a projected dose. The administered dose in Part 2, Cohort 3 will be based on PK/PD results from preceding dosing cohorts and will not exceed the maximum exposure observed in SAD (Part 1).	Drug: GSK3732394; It is composed of an anti-CD4 adnectin, an anti-N17 adnectin, and a peptide inhibitor. This will be provided as a solution for injection in 1 (milliliter) mL glass vials with the unit dose strength of 100 mg/mL; Drug: Placebo; Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants With Non-serious Adverse Event (SAEs) and SAEs	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose: results in death and is life-threatening which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly, or any other situation that require medical or scientific judgement. Number of participants with common more than or equal to (>=)5 percent (%) non-serious AEs and SAEs are presented.	Up to Day 28
Part 2: Number of Participants With Non-SAEs and SAEs	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose: results in death and is life-threatening which requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity and birth defect or congenital anomaly, or any other situation that require medical or scientific judgement. All AEs were planned to be collected from the start of treatment until the follow-up visit.	Up to Day 49
Part 1: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline	Blood samples were collected for the analysis of following clinical chemistry parameters: Glucose, alkaline phosphatase, alanine aminotransferase (ALT), amylase, aspartate aminotransferase (AST), direct bilirubin, total bilirubin, calcium, creatinine, potassium, lipase and sodium. The clinical chemistry abnormalities were graded using the Division of Acquired immunodeficiency syndrome (DAIDS) criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severe condition. Baseline is defined as the latest pre-dose assessment. Number of participants with clinical chemistry parameters by maximum grade increase post-Baseline is presented.	Up to Day 28
Part 2: Number of Participants With Clinical Chemistry Parameters by Maximum Grade Increase Post-Baseline	Blood samples were planned to be collected for the analysis of the following clinical chemistry parameters: Glucose, alkaline phosphatase, ALT, amylase, AST, direct and total bilirubin, calcium, creatinine, potassium, lipase and sodium. Baseline is defined as the latest pre-dose assessment.	Up to Day 49
Part 1: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline	Blood samples were collected for the analysis of following hematology parameters: Cluster of differentiation (CD) 4 cells, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. The hematology abnormalities were graded using the DAIDS criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates more severe condition. Baseline is defined as the latest pre-dose assessment. Number of participants with hematology parameters by maximum grade increase post-Baseline is presented.	Up to Day 28
Part 2: Number of Participants With Hematology Parameters by Maximum Grade Increase Post-Baseline	Blood samples were planned to be collected for the analysis of the following hematology parameters: CD4 cells, hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. Baseline is defined as the latest pre-dose assessment.	Up to Day 49
Part 1: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline	Urine samples were collected for the analysis of urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. The urinalysis abnormalities were graded using the DAIDS criteria and grades were derived based on numeric criteria as defined in DAIDS Version 2.1 and did not take into consideration of clinical signs or symptoms. Baseline is defined as the latest pre-dose assessment. Number of participants with urinalysis parameters by any increase in discrete or character values post Baseline is presented.	Up to Day 28
Part 2: Number of Participants With Urinalysis Parameters by Any Increase in Discrete or Character Values Post Baseline	Urine samples were planned to be collected for the analysis of urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, protein and urobilinogen. Baseline is defined as the latest pre-dose assessment.	Up to Day 49
Part 1: Number of Participants With Worst Case Pulse Rate Post Baseline	Pulse rate was measured in a semi-supine position after 5 minutes of rest. Participants are counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose value category are unchanged (e.g., High to High), or whose value became within range, are recorded in the "To within Range or No Change" category. Participants with missing Baseline value are assumed to have within range value. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment. Number of participants with pulse rate change to low or to high and no change post Baseline is presented.	Up to Day 28
Part 2: Number of Participants With Worst Case Pulse Rate Post Baseline	Pulse rate was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment.	Up to Day 49
Part 1: Change From Baseline in Body Temperature	Body temperature was measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.	Baseline and at Day 1 (1, 2, 4, 8, 12 hours), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in Body Temperature	Body temperature was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline and Up to Day 49
Part 1: Change From Baseline in Respiratory Rate	Respiratory rate was measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.	Baseline and at Day 1 (1, 2, 4, 8, 12 hours), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in Respiratory Rate	Respiratory rate was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline and Up to Day 49
Part 1: Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Post Baseline	SBP and DBP was measured in a semi-supine position after 5 minutes of rest. Participants are counted in the worst case category that their value changes to low, within range or no change, or high), unless there is no change in their category. Participants whose value category are unchanged (e.g., High to High), or whose value became within range, are recorded in the "To within Range or No Change" category. Participants with missing Baseline value are assumed to have within range value. Participants were counted twice if the participant had both values that changed 'To Low' and 'To High'. Baseline is defined as the latest pre-dose assessment. Number of participants with SBP and DBP change to low and to high and no change post Baseline is presented.	Up to Day 28
Part 2: Number of Participants With Worst Case SBP and DBP Post Baseline	SBP and DBP was planned to be measured in a semi-supine position after 5 minutes of rest. Baseline is defined as the latest pre-dose assessment.	Up to Day 49
Part 1: Number of Participants With Clinical Significant Abnormal Electrocardiogram (ECG) Findings	A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of 5 minutes. Twelve lead ECGs were obtained by using an automated ECG machine. Number of participants with clinical significant abnormal ECG findings are presented.	Pre-dose, 4, 12 hours on Day 1, 24 hours on Day 2, Days 8, 14, 17 and 28
Part 2: Number of Participants With Clinical Significant Abnormal ECG Findings	12-lead ECG recordings was planned to be measured.	Up to Day 49

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Area Under the Plasma Concentration Time Curve From Zero to t (AUC[0-t]) Following Single Dose Administration of GSK3732394	Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.	Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: AUC(0-t) After Repeat Dosing of GSK3732394 in First Week	Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.	Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) Following Single Dose Administration of GSK3732394	Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.	Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: AUC(0-infinity) After Repeat Dosing of GSK3732394 in First Week	Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.	Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Part 1: Maximum Observed Concentration (Cmax) Following Single Dose Administration of GSK3732394	Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.	Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Cmax After Repeat Dosing of GSK3732394 in First Week	Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.	Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Part 2: Cmax After Repeat Dosing of GSK3732394 in Last Week	Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.	Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 1: Time of Occurrence of Cmax (Tmax) After Single Dose Administration of GSK3732394	Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were calculated using standard non-compartmental analysis.	Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Tmax After Repeat Dosing of GSK3732394 in First Week	Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.	Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Part 2: Tmax After Repeat Dosing of GSK3732394 in Last Week	Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.	Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 1: Lag Time Before Observation of Drug Concentrations (Tlag) After Single Dose Administration of GSK3732394	Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were calculated using standard non-compartmental analysis.	Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Tlag After Repeat Dosing of GSK3732394 in First Week	Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.	Day 1 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6 and 7
Part 1: Last Observable Concentration (Clast) After Single Dose Administration of GSK3732394	Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.	Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 1: Time of Last Observable Concentration (Tlast) After Single Dose Administration of GSK3732394	Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.	Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 1: Apparent Terminal Phase Half-life (t1/2) After Single Dose Administration of GSK3732394	Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.	Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: T1/2 After Repeat Dosing of GSK3732394 in Last Week	Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.	Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 1: Apparent Clearance (CL/F) After Single Dose Administration of GSK3732394	Blood samples were collected at indicated time points for PK analysis of GSK3732394. PK parameters were analyzed using standard non-compartmental analysis.	Day 1 (Pre-dose, 0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: CL/F After Repeat Dosing of GSK3732394 in Last Week	Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.	Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 2: Area Under the Concentration Time Curve at Steady State Within the Dosing Interval (AUC[0-tau]) After Repeat Dosing of GSK3732394 in Last Week	Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.	Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 2: Trough Concentration (Ctrough) After Repeat Dosing of GSK3732394 in Last Week	Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394.	Day 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 23, 24, 25, 26, 27 and 28
Part 2: Accumulation Ratio Using AUC(0-tau) (RAUC[0-tau]) After Repeat Dosing of GSK3732394	Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RAUC(0-tau) was planned to be calculated as the ratio of AUC(0-tau) on week 4 to AUC(0-tau) on week 1 .	Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28
Part 2: Accumulation Ratio Using Cmax (RCmax) After Repeat Dosing of GSK3732394	Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RCmax was planned to be calculated as the ratio of Cmax on Week 4 to Cmax on Week 1.	Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28
Part 2: Accumulation Ratio Using Ctrough (RCtrough) After Repeat Dosing of GSK3732394	Blood samples were planned to be collected at indicated time points for PK analysis of GSK3732394. RCtrough was planned to be calculated as the ratio of Ctrough on Week 4 to Ctrough on Week 1.	Days 1 and 22 (pre-dose, 0.5, 1, 2, 4, 8 and 12 hours), Days 2, 3, 4, 5, 6, 7, 23, 24, 25, 26, 27 and 28
Part 1: Change From Baseline in Percent of CD4 Receptor Occupancy (RO) After Single Dose Administration of GSK3732394	Blood samples were collected at indicated time points for Pharmacodynamic (PD) analysis of CD4 receptors occupied by GSK3732394 on CD4+ T cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.	Baseline, Day 1 (0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in Percent of CD4 RO After Multiple Dose Administration of GSK3732394	Blood samples were planned to be collected at indicated time points for PD analysis of CD4 receptors occupied by GSK3732394 on CD4+ T cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline and up to Day 49
Part 1: Change From Baseline in CD3+ Cells Following Single Dose Administration of GSK3732394	Blood samples were collected at indicated time points for analysis of CD3+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.	Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in CD3+ Cells Following Multiple Dose Administration of GSK3732394	Blood samples were planned to be collected at indicated time points for analysis of CD3+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline and up to Day 49
Part 1: Change From Baseline in CD4+ Cells Following Single Dose Administration of GSK3732394	Blood samples were collected at indicated time points for analysis of CD4+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.	Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in CD4+ Cells Following Multiple Dose Administration of GSK3732394	Blood samples were planned to be collected at indicated time points for analysis of CD4+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline and up to Day 49
Part 1: Change From Baseline in CD8+ Cells Following Single Dose Administration of GSK3732394	Blood samples were collected at indicated time points for analysis of CD8+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.	Baseline, Days 2, 3, 5, 8, 11, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in CD8+ Cells Following Multiple Dose Administration of GSK3732394	Blood samples were planned to be collected at indicated time points for analysis of CD8+ cells. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline and up to Day 49
Part 1: Change From Baseline in CD4+ Cell Median Fluorescence Intensity (MFI) Following Single Dose Administration of GSK3732394	Blood samples were collected at indicated time points for analysis of CD4+ cell MFI. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline value is defined as post-dose value minus Baseline value.	Baseline, Day 1 (0.5, 1, 2, 4, 8, 12 hours), Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 21, 24 and 28
Part 2: Change From Baseline in CD4+ Cell MFI Following Multiple Dose Administration of GSK3732394	Blood samples were planned to be collected at indicated time points for analysis of CD4+ cell MFI. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.	Baseline and up to Day 49
Part 1: Number of Participants With Anti-GSK3732394 Antibodies on Day 28	Serum samples were collected to analyze antibodies against GSK3732394. The presence of anti-GSK3732394 antibodies was determined in serum samples using a validated bioanalytical method, which included a screening assay, confirmation assay and titer analysis. Positive samples were further characterized with additional assays to determine the specificity of the anti-GSK3732394 antibodies. Number of participants with presence of anti-GSK3732394 antibodies are presented.	Day 28
Part 2: Number of Participants With Anti-GSK3732394 Antibodies	Serum samples were planned to be collected to analyze antibodies against GSK3732394.	Up to Day 49
Part 1: Titer of Anti-drug Antibodies (ADAs) Against GSK3732394 on Day 28	Serum samples were collected to analyze the titers of antibodies against GSK3732394. The presence of anti-GSK3732394 antibodies was determined in serum samples using a validated bioanalytical method, which included a screening assay, confirmation assay and titer analysis. Positive samples were further characterized with additional assays to determine the specificity of the anti-GSK3732394 antibodies. Positive samples were titrated to obtain the titers of antibodies.	Day 28
Part 2: Titer of ADAs Against GSK3732394	Serum samples were planned to be collected to analyze the titers of antibodies against GSK3732394.	Up to Day 49

Collaborators and Investigators

• Sponsor: ViiV Healthcare

Publications and helpful links

General Publications

• Krystal M, Chabria S, Austin D, Wolstenholme A, Wensel D, Lataillade M, Abberbock J, Baker M, Ackerman P. A Phase 1 randomized study of GSK3732394, an investigational long-acting biologic treatment regimen for HIV-1 infection. Antivir Ther. 2022 Oct;27(5):13596535221131164. doi: 10.1177/13596535221131164.

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2019
• Primary Completion (Actual): March 23, 2020
• Study Completion (Actual): March 23, 2020

Study Registration Dates

• First Submitted: June 10, 2019
• First Submitted That Met QC Criteria: June 10, 2019
• First Posted (Actual): June 13, 2019

Study Record Updates

• Last Update Posted (Actual): October 25, 2021
• Last Update Submitted That Met QC Criteria: October 4, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: DAIDS, FTIH, HIV-1, MAD, SAD
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: 207863

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the 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 can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No