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

NCT ID: NCT03984812

Last Updated: 2021-10-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-17
• Study Completion Date: 2020-03-23

Brief Summary

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.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

GSK3732394

Intervention Type: DRUG

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

Intervention Type: DRUG

Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.

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.

Group Type: EXPERIMENTAL

GSK3732394

Intervention Type: DRUG

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

Intervention Type: DRUG

Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.

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.

Group Type: EXPERIMENTAL

GSK3732394

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

GSK3732394

Intervention Type: DRUG

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

Intervention Type: DRUG

Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.

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.

Group Type: EXPERIMENTAL

GSK3732394

Intervention Type: DRUG

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

Intervention Type: DRUG

Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.

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.

Group Type: EXPERIMENTAL

GSK3732394

Intervention Type: DRUG

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

Intervention Type: DRUG

Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.

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.

Group Type: EXPERIMENTAL

GSK3732394

Intervention Type: DRUG

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

Intervention Type: DRUG

Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.

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.

Group Type: EXPERIMENTAL

GSK3732394

Intervention Type: DRUG

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

Intervention Type: DRUG

Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.

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).

Group Type: EXPERIMENTAL

GSK3732394

Intervention Type: DRUG

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

Intervention Type: DRUG

Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.

Interventions

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

Intervention Type: DRUG

Placebo

Placebo will comprise of 0.9% weight per volume (w/v) sodium chloride.

Intervention Type: DRUG

Eligibility 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 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

ViiV Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

GSK Investigational Site

Baltimore, Maryland, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36191080 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

207863

Identifier Type: -

Identifier Source: org_study_id