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

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ClinicalTrials.gov Identifier: NCT03984812
Recruitment Status : Recruiting
First Posted : June 13, 2019
Last Update Posted : July 2, 2019
Sponsor:
Information provided by (Responsible Party):
ViiV Healthcare

Brief Summary:
This is a phase 1, 2 part, double-blind (sponsor-unblinded), randomized, placebo-controlled, FTIH study in a combined single-ascending and multiple-ascending dose to assess the safety, tolerability, and PK/pharmacodynamics (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 study. Part 1 will be designed as a single ascending dose (SAD) and Part 2 as multiple ascending dose (MAD). 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 required. Part 2 will consist of up to three ascending repeat-dose cohorts (MAD Cohorts 1, 2, and 3), randomized to four weekly doses of GSK3732394: PBO in 6:2 ratio on Days 1, 8, 15, and 22.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: GSK3732394 Drug: Placebo Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: In Part 1 of the study each of the subjects in the SAD cohorts (SAD Cohorts 1-5; SAD Cohort 6 is a possible expansion cohort that will be added as needed) will receive a single dose of blinded GSK3732394 or blinded PBO (GSK3732394: PBO = 6:2), per their randomization assignment. Part 2 will consist of up to three ascending repeat-dose cohorts (MAD Cohorts 1, 2, and 3), each with 8 subjects (GSK3732394: PBO = 6:2) will receive four weekly doses of GSK3732394 or PBO on Days 1, 8, 15, and 22.
Masking: Double (Participant, Investigator)
Masking Description: This is double-blind (sponsor-unblinded) study with subjects and the site staff blinded, except for an unblinded pharmacist at the site who will prepare the blinded drug product. The blind may be broken if, in the opinion of the investigator, it is in the subject's best interest for the investigator to know the study treatment assignment.
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK3732394 in Healthy Participants
Actual Study Start Date : June 17, 2019
Estimated Primary Completion Date : April 6, 2020
Estimated Study Completion Date : April 6, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Part 1: Subjects receiving GSK3732394 10mg
GSK3732394 10 milligram (mg) or PBO will be administered by subcutaneous (SC) injection to the subjects. This is projected dose, final dose will be based on PK/PD results.
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: Part 1: Subjects receiving GSK3732394 40 mg
GSK3732394 40 mg or PBO will be administered by SC injection to the subjects. This is projected dose, final 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

Experimental: Part 1: Subjects receiving GSK3732394 130 mg
GSK3732394 130 mg or PBO will be administered by SC injection to the subjects. This is projected dose, final 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

Experimental: Part 1: Subjects receiving GSK3732394 350 mg
GSK3732394 350 mg or PBO will be administered by SC injection to the subjects. This is projected dose, final 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

Experimental: Part 1: Subjects receiving GSK3732394 600 mg
GSK3732394 600 mg or PBO will be administered by SC injection to the subjects. This is projected dose, final 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

Experimental: Part 1: Subjects receiving GSK3732394 800 mg
GSK3732394 800 mg or PBO will be administered by SC injection to the subjects. This is projected dose, final 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

Placebo Comparator: Part 1: Subjects receiving Placebo
Placebo will be administered by SC injection to the subjects.
Drug: Placebo
Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.

Experimental: Part 2: Subjects receiving GSK3732394 130 mg
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 projected dose, final 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

Experimental: Part 2: Subjects receiving GSK3732394 400 mg
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 projected dose, final 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

Experimental: Part 2: Subjects receiving GSK3732394 600 mg
GSK3732394 600 mg or PBO will be administered by SC injection to the subjects on Days 1, 8, 15, and 22 of the study. Final 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

Placebo Comparator: Part 2: Subjects receiving Placebo
Placebo will be administered by SC injection to the subjects.
Drug: Placebo
Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.




Primary Outcome Measures :
  1. Part 1: Number of subjects with any adverse event (AE) and serious adverse events (SAE) [ Time Frame: Up to Day 28 ]
    An AE is any untoward medical occurrence in a clinical study subject, 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 judgment.

  2. Part 2: Number of subjects with any AE and SAE [ Time Frame: Up to Day 49 ]
    An AE is any untoward medical occurrence in a clinical study subject, 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 judgment.

  3. Part 1: Number of subjects with abnormal clinical chemistry parameters [ Time Frame: Up to Day 28 ]
    Blood samples will be collected for analysis of chemistry parameters.

  4. Part 2: Number of subjects with abnormal clinical chemistry parameters [ Time Frame: Up to Day 49 ]
    Blood samples will be collected for analysis of chemistry parameters.

  5. Part 1: Number of subjects with abnormal hematology parameters [ Time Frame: Up to Day 28 ]
    Blood samples will be collected for analysis of hematology parameters.

  6. Part 2: Number of subjects with abnormal hematology parameters [ Time Frame: Up to Day 49 ]
    Blood samples will be collected for analysis of hematology parameters.

  7. Part 1: Number of subjects with abnormal urinalysis parameters [ Time Frame: Up to Day 28 ]
    Urine samples will be collected for analysis of urine parameters.

  8. Part 2: Number of subjects with abnormal urinalysis parameters [ Time Frame: Up to Day 49 ]
    Urine samples will be collected for analysis of urine parameters.

  9. Part 1: Number of subjects with abnormal pulse rate [ Time Frame: Up to Day 28 ]
    Pulse rate will be measured in semi-supine position.

  10. Part 2: Number of subjects with abnormal pulse rate [ Time Frame: Up to Day 49 ]
    Pulse rate will be measured in semi-supine position.

  11. Part 1: Number of subjects with abnormal body temperature [ Time Frame: Up to Day 28 ]
    Body temperature will be measured in semi-supine position.

  12. Part 2: Number of subjects with abnormal body temperature [ Time Frame: Up to Day 49 ]
    Body temperature will be measured in semi-supine position.

  13. Part 1: Number of subjects with abnormal respiratory rate [ Time Frame: Up to Day 28 ]
    Respiratory rate will be measured in semi-supine position.

  14. Part 2: Number of subjects with abnormal respiratory rate [ Time Frame: Up to Day 49 ]
    Respiratory rate will be measured in semi-supine position.

  15. Part 1: Number of subjects with abnormal systolic blood pressure (SBP) and diastolic blood pressure (DBP) [ Time Frame: Up to Day 28 ]
    Blood pressure will be measured in semi-supine position with at least 5 minutes of rest.

  16. Part 2: Number of subjects with abnormal SBP and DBP [ Time Frame: Up to Day 49 ]
    Blood pressure will be measured in semi-supine position with at least 5 minutes of rest.

  17. Part 1: Number of subjects with abnormal electrocardiogram (ECG) findings as a measure of safety and tolerability [ Time Frame: Up to Day 28 ]
    A 12-lead ECG will be obtained in semi supine position.

  18. Part 2: Number of subjects with abnormal electrocardiogram (ECG) findings as a measure of safety and tolerability [ Time Frame: Up to Day 49 ]
    A 12-lead ECG will be obtained in semi supine position.


Secondary Outcome Measures :
  1. Part 1: Area under the plasma concentration time curve from zero to t (AUC0-t) of GSK3732394 (single dose) [ Time Frame: Day 1 (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7,8,9,10,11,12,13,14,17,21,24, and 28 post-dose ]
    Blood samples will be collected at indicated time points for analysis of AUC(0-t).

  2. Part 2: AUC0-t of GSK3732394 [ Time Frame: Day 1, Day 22: (pre-dose),0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Days 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Days 16,17,18,19,20,21,23,24,25,26,27,28,29,30,31,32,33,34,35,38,42,46, and 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of AUC (0-t).

  3. Part 1: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC0-inf) of GSK3732394 (single dose) [ Time Frame: Day 1 (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7,8,9,10,11,12,13,14,17,21,24, and 28 post-dose ]
    Blood samples will be collected at indicated time points for analysis of AUC(0-inf).

  4. Part 2: AUC(0-inf) of GSK3732394 [ Time Frame: Day 1,22: (pre-dose), 0.5,1,2,4,8,12 hours, Day 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Day 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of AUC (0-inf).

  5. Part 1: Maximum observed concentration (Cmax) of GSK3732394 (single dose) [ Time Frame: Day 1 (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7,8,9,10,11,12,13,14,17,21,24, and 28 post-dose ]
    Blood samples will be collected at indicated time points for analysis of Cmax.

  6. Part 2: Cmax of GSK3732394 (first week) [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Day 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of Cmax.

  7. Part 2: Cmax of GSK3732394 (repeated once weekly [QW] dosing) (last week) [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Day 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Day 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, and 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of Cmax.

  8. Part 1: Time of occurrence of Cmax (Tmax) of GSK3732394 (single dose) [ Time Frame: Day 1 (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7,8,9,10,11,12,13,14,17,21,24,and 28 post-dose ]
    Blood samples will be collected at indicated time points for analysis of tmax.

  9. Part 2: Tmax of GSK3732394 (first week) [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Day 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of Tmax.

  10. Part 2: Tmax of GSK3732394 (repeated QW dosing) (last week) [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Day 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Day 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, and 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of Tmax.

  11. Part 1: Lag time (tlag) of GSK3732394 (single dose) [ Time Frame: Day 1 (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7,8,9,10,11,12,13,14,17,21,24, and 28 post-dose ]
    Blood samples will be collected at indicated time points for analysis of tlag.

  12. Part 2: Tlag of GSK3732394 (repeated QW dosing) (first week) [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Day 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of Tlag.

  13. Part 1: Last observable concentration (Clast) of GSK3732394 (single dose) [ Time Frame: Day 1 (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7,8,9,10,11,12,13,14,17,21,24, and 28 post-dose ]
    Blood samples will be collected at indicated time points for analysis of Clast.

  14. Part 1: Time of last observable concentration (Tlast) GSK3732394 (single dose) [ Time Frame: Day 1 (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7,8,9,10,11,12,13,14,17,21,24, and 28 post-dose ]
    Blood samples will be collected at indicated time points for analysis of Tlast.

  15. Part 1: Apparent terminal phase half-life (t1/2) GSK3732394 (single dose) [ Time Frame: 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 post-dose ]
    Blood samples will be collected at indicated time points for analysis of t1/2.

  16. Part 2: T1/2 of GSK3732394 (repeated QW dosing) (last week) [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Day 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, and 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of t1/2.

  17. Part 1: Apparent clearance (CL/F) of GSK3732394 (single dose) [ Time Frame: 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 post-dose ]
    Blood samples will be collected at indicated time points for analysis of CL/F.

  18. Part 2: CL/F of GSK3732394 (repeated QW dosing) (last week) [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Day 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Days 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, and 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of CL/F.

  19. Part 2: AUC(0-tau) of GSK3732394 (last week) [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Days 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Days 16,17,18,19,20,21,23,24,25,26,27,28,29,30,31,32,33,34,35,38,42,46, and 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of AUC (0-tau).

  20. Part 2: Trough concentration (Ctrough) of GSK3732394 (repeated QW dosing) (last week) [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Day 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Day 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, and 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of Ctrough.

  21. Part 2: AUC(0- tau) on week 4 to AUC(0-tau) on week 1 (RAUC[0-tau]) of GSK3732394 first dose [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Day 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, and 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of RAUC(0-tau).

  22. Part 2: RAUC(0-tau) of GSK3732394 last dose [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Day 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, and 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of RAUC (0-tau).

  23. Part 2: Cmax on Week 4 to Cmax on Week 1 (RCmax) of GSK3732394 first dose [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Day 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, and 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of RCmax.

  24. Part 2: RCmax of GSK3732394 last dose [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Day 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of RCmax.

  25. Part 2: Ctrough on Week 4 to Ctrough on Week 1 (RCtrough) of GSK3732394 first dose [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Day 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, and 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of RCtrough.

  26. Part 2: RCtrough of GSK3732394 last dose [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Day 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Day 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, and 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of RCtrough.

  27. Part 1: Percent of CD4 receptor occupancy (RO) of GSK3732394 [ Time Frame: Day 1 (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7,8,9,10,11,12,13,14,17,21,24, and 28 post-dose ]
    Blood samples will be collected at indicated time points for analysis of percent CD4 RO.

  28. Part 2: Percent of CD4 RO of GSK3732394 [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Day 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Days 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, and 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of percent CD4 RO.

  29. Part 1:Percentage of Receptor occupancy of GSK3732394 [ Time Frame: Day 1 (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7,8,9,10,11,12,13,14,17,21,24, and 28 post-dose ]
    Blood samples will be collected at indicated time points for analysis of percentage of RO.

  30. Part 2: Percentage of Receptor occupancy of GSK3732394 [ Time Frame: Day 1, Day 22: (pre-dose), 0.5,1,2,4,8,12 hours, Days 2,3,4,5,6,7, Day 8: (pre-dose), 0hour, Day 9,10,11,12,1,3,14,Day 15 (pre-dose), 0hour, Day 16,17,18,19,20,21, 23,24,25,26,27,28,29,30, 31,32,33,34,35,38,42,46, and 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of percentage of RO.

  31. Part 1: Change from Baseline in CD3 [ Time Frame: Baseline (Day -1), Days 2, 3, 5, 8, 11,14, 17, 21,24, and 28 post-dose ]
    Blood samples will be collected at indicated time points.

  32. Part 2: Change from Baseline in CD3 [ Time Frame: Baseline (Day -1), Days 2, 3, 5, 8, 9, 11, 15 (pre-dose), 16, 18, 22 (pre-dose), 23, 27, 29, 32, 35, 38, 42, 46, and 49 post-dose ]
    Blood samples will be collected at indicated time points.

  33. Part 1: Change from Baseline in CD4 [ Time Frame: Baseline (Day -1), Days 2, 3, 5, 8, 11,14, 17, 21,24, and 28 post-dose ]
    Blood samples will be collected at indicated time points.

  34. Part 2: Change from Baseline in CD4 [ Time Frame: Baseline (Day -1), Days 2, 3, 5, 8, 9, 11, 15 (pre-dose), 16, 18, 22 (pre-dose), 23, 27, 29, 32, 35, 38, 42, 46, and 49 post-dose ]
    Blood samples will be collected at indicated time points.

  35. Part 1: Change from Baseline in CD8 [ Time Frame: Baseline (Day -1), Days 2, 3, 5, 8, 11,14, 17, 21,24, and 28 post-dose ]
    Blood samples will be collected at indicated time points.

  36. Part 2: Change from Baseline in CD8 [ Time Frame: Baseline (Day -1), Days 2, 3, 5, 8, 9, 11, 15 (pre-dose), 16, 18, 22 (pre-dose), 23, 27, 29, 32, 35, 38, 42, 46, and 49 post-dose ]
    Blood samples will be collected at indicated time points.

  37. Part 1: Change from Baseline in CD4 mean fluorescence intensity (MFI) [ Time Frame: Baseline (Day -1), Days 2, 3, 5, 8, 11,14, 17, 21,24, and 28 post-dose ]
    Blood samples will be collected at indicated time points for analysis of MFI.

  38. Part 2: Change from Baseline in CD4 MFI [ Time Frame: Baseline (Day -1), Days 2, 3, 5, 8, 9, 11, 15 (pre-dose), 16, 18, 22 (pre-dose), 23, 27, 29, 32, 35, 38, 42, 46, and 49 post-dose ]
    Blood samples will be collected at indicated time points for analysis of MFI.

  39. Part 1: Number of subjects with anti-GSK3732394 antibodies [ Time Frame: Day -1, Days 14, 21, and 28 post-dose ]
    Serum samples will be collected at the time points indicated to analyze antibodies against GSK3732394.

  40. Part 2: Number of subjects with anti-GSK3732394 antibodies [ Time Frame: Day -1, Day 15 (pre-dose), Days 22 (pre-dose), 29, 35, 42, and 49 post-dose ]
    Serum samples will be collected at the time points indicated to analyze antibodies against GSK3732394.

  41. Part 1: Titer of anti-drug antibodies (ADAs) against GSK3732394 [ Time Frame: Day -1, Days 14, 21, and 28 post-dose ]
    Serum samples will be collected at the time points indicated to analyze the titers of antibodies against GSK3732394.

  42. Part 2: Titer of ADAs against GSK3732394 [ Time Frame: Day -1, Day 15 (pre-dose), Days 22 (pre-dose), 29, 35, 42, and 49 post-dose ]
    Serum samples will be collected at the time points indicated to analyze the titers of antibodies against GSK3732394.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 subjects 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 chest x-rays (posterior anterior and lateral, if TB test results are positive), 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03984812


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
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United States, Maryland
GSK Investigational Site Recruiting
Baltimore, Maryland, United States, 21225
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Ronald Goldwater         
Sponsors and Collaborators
ViiV Healthcare
Investigators
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Study Director: GSK Clinical Trials ViiV Healthcare

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Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT03984812     History of Changes
Other Study ID Numbers: 207863
First Posted: June 13, 2019    Key Record Dates
Last Update Posted: July 2, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
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.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ViiV Healthcare:
DAIDS, FTIH, HIV-1, MAD, SAD
Additional relevant MeSH terms:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases