A Proof of Concept Study of GSK3640254 in Human Immunodeficiency Virus-1 (HIV-1) Infected Treatment-naive Adults

NCT03784079 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 208132
• Study Type: interventional
• Target: 34
• Locations: 6 countries
• Sites: 23

Brief Summary

Infection with HIV-1 continues to be a serious health threat throughout the world. Chronic exposure to combination anti-retroviral therapy identified anti-retroviral associated long-term toxicities. Hence, there is a need to prevent these co-morbidities. GSK3640254 is a next-generation HIV-1 Maturation Inhibitor (MI) which may be effective for HIV-1 infection. This study will evaluate the antiviral effect, safety, tolerability and pharmacokinetics/ pharmacodynamics of GSK3640254 in HIV-1 infected treatment-naive adults. This study will consists of two parts; Part 1 and Part 2. Part 1 will evaluate two active doses of GSK3640254, 200 milligrams (mg) (Cohort 1) and 10 mg (Cohort 2) along with placebo to match GSK3640254 Mesylate salt. Part 2 will evaluate three active doses of GSK3640254. Dose level 1 of GSK3640254 that can provide at least 30 percent of the maximum effect (Cohort 1), dose level 2 of GSK3640254 that can provide at least 75 percent of the maximum effect (Cohort 2) and dose level 3 of GSK3640254 that can provide at least 90 percent of the maximum effect (Cohort 3). These doses are anticipated to be 5 mg, 40 mg and 100 mg respectively, but could be modified based on data obtained in Part 1. Subjects will also receive placebo to match GSK3640254 Mesylate salt in Part 2 of the study. All doses will be administered after a moderate fat meal. This study will consist of Screening period (up to 14 days), Treatment period (Day 1- Day 10), post-dose Follow-up (Day 11- Day 17) and final Follow-up (Day 18-24). A total of approximately 34 subjects will be enrolled, of which, 14 subjects will be randomized in Part 1 and 20 in Part 2 of the study. Six subjects will be enrolled in each of the active dose cohorts and 2 subjects will be enrolled in each of the placebo cohorts.

Conditions

HIV Infections

Keywords

HIV-1, Antiviral Effect, GSK3640254, Proof of Concept

Outcome Measures

Primary Outcomes (2)

• Part 1: Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 11

  Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. A HIV-1 RNA polymerase chain reaction (PCR) assay with a lower limit of detection (LLOD) of 50 copies per milliliter was used. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  Baseline (Day 1) and Day 11

• Part 2: Maximum Change From Baseline in Plasma HIV-1 RNA at Day 8

  Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. An HIV-1 RNA PCR assay with an LLOD of 50 copies per milliliter was used. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

  Baseline (Day 1) and Day 8

Secondary Outcomes (113)

• Part 1: Number of Participants With Non-Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

  Up to Day 24

• Part 2: Number of Participants With Non-SAEs and SAEs

  Up to Day 12

• Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

  Baseline (Day 1) and Visit 5 (Days 8 to 10)

• Part 1: Change From Baseline in Hematology Parameter: Hemoglobin

  Baseline (Day 1) and Visit 5 (Days 8 to 10)

• Part 1: Change From Baseline in Hematology Parameter: Hematocrit

  Baseline (Day 1) and Visit 5 (Days 8 to 10)

Study Arms (7)

Part 1: GSK3640254 10 mg

EXPERIMENTAL

Participants will receive GSK3640254 10 milligram (mg), capsules, orally for 10 days.

Drug: GSK3640254

Part 1: GSK3640254 200 mg

EXPERIMENTAL

Participants will receive GSK3640254 200 mg, capsules, orally for 10 days.

Drug: GSK3640254

Part 1: Placebo

PLACEBO COMPARATOR

Participants will receive placebo capsules, orally for 10 days.

Drug: Placebo matching GSK3640254 Mesylate salt

Part 2: GSK3640254 40 mg

EXPERIMENTAL

Participants will receive GSK3640254 40 mg, capsules, orally for 7 days.

Drug: GSK3640254

Part 2: GSK3640254 80 mg

EXPERIMENTAL

Participants will receive GSK3640254 80 mg, capsules, orally for 7 days.

Drug: GSK3640254

Part 2: GSK3640254 140 mg

EXPERIMENTAL

Participants will receive GSK3640254 140 mg, capsules, orally for 7 days.

Drug: GSK3640254

Part 2: Placebo

PLACEBO COMPARATOR

Participants will receive placebo capsules, orally for 7 days.

Drug: Placebo matching GSK3640254 Mesylate salt

Interventions

GSK3640254 DRUG

GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.

Part 1: GSK3640254 10 mg; Part 1: GSK3640254 200 mg; Part 2: GSK3640254 140 mg; Part 2: GSK3640254 40 mg; Part 2: GSK3640254 80 mg

Placebo matching GSK3640254 Mesylate salt DRUG

Placebo to match GSK3640254 Mesylate salt will be given as an oral capsule along with 240 mL of water

Part 1: Placebo; Part 2: Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
• Subjects who are healthy (other than HIV infection) as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, laboratory tests, and cardiac monitoring.
• Screening Cluster of designation 4 positive (CD4+) T-cell count \>=350 cells per millimeter cube (cells/mm\^3).
• Documented HIV infection and Screening plasma HIV-1 RNA \>=5000 copies/milliliter (mL). A single repeat of this test is allowed within a single Screening period to determine eligibility.
• Treatment-naive: No anti-retrovirals (in combination or monotherapy) received after the diagnosis of HIV-1 infection.
• Body weight \>=50.0 kilograms (kg) (110 Pounds) for men and \>=45.0 kg (99 pounds) for women and body mass index (BMI) within the range 18.5-31.0 kg/meter square (kg/m\^2) (inclusive).
• A female subject is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP).
• Capable of giving signed informed consent.

You may not qualify if:

• Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to starting study treatment.
• Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study treatment and positive on reflex to Hepatitis C RNA.
• ALT \>2 times upper limit of normal (ULN). A single repeat of ALT is allowed within a single Screening period to determine eligibility.
• Bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent).
• Subjects with primary HIV infection, evidenced by acute retroviral syndrome (example given \[e.g.\], 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.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones);
• A pre-existing condition interfering with normal gastrointestinal anatomy or motility (e.g., gastroesophageal reflux disease \[GERD\], gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs or render the subject unable to take oral study treatment.
• Any acute laboratory abnormality at screen which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
• Any Grade 2-4 laboratory abnormality at screen, with the exception of creatine phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides, etc), and ALT (described above), will exclude a subject from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat of any lab abnormality is allowed within a single screening period to determine eligibility.
• Any history of significant underlying psychiatric disorder, including but not limited to schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder.
• Any history of major depressive disorder with or without suicidal features, or anxiety disorders, that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (\>6 months) outpatient treatment. Subjects with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy (\<6 months) without inpatient treatment and are currently well-controlled clinically or resolved may be considered for entry after discussion and agreement with the ViiV Medical Monitor.
• Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the investigator (with or without psychiatric evaluation), could interfere with the subject's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the subject.
• Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
• The subject has participated in a clinical trial and has received an investigational product within the 30 days prior to the first dosing day in the current study.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (23)

GSK Investigational Site

Bakersfield, California, 93301, United States

Location

GSK Investigational Site

Orlando, Florida, 32803, United States

Location

GSK Investigational Site

Marseille, 13003, France

Location

GSK Investigational Site

Paris, 75018, France

Location

GSK Investigational Site

Tourcoing, 59208, France

Location

GSK Investigational Site

Munich, Bavaria, 81675, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60590, Germany

Location

GSK Investigational Site

Rome, Lazio, 00149, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20127, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20157, Italy

Location

GSK Investigational Site

Johannesburg, Gauteng, 2113, South Africa

Location

GSK Investigational Site

Bloemfontein, 9301, South Africa

Location

GSK Investigational Site

Durban, 4001, South Africa

Location

GSK Investigational Site

Alicante, 03010, Spain

Location

GSK Investigational Site

Badalona, 08916, Spain

Location

GSK Investigational Site

Barcelona, 08025, Spain

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Barcelona, 08907, Spain

Location

GSK Investigational Site

Madrid, 28006, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Seville, 41013, Spain

Location

Related Publications (1)

• Spinner CD, Felizarta F, Rizzardini G, Philibert P, Mitha E, Domingo P, Stephan CJ, DeGrosky M, Bainbridge V, Zhan J, Dumitrescu TP, Jeffrey JL, Xu J, Halliday F, Gan J, Johnson M, Gartland M, Joshi SR, Lataillade M. Phase IIa Proof-of-Concept Evaluation of the Antiviral Efficacy, Safety, Tolerability, and Pharmacokinetics of the Next-Generation Maturation Inhibitor GSK3640254. Clin Infect Dis. 2022 Sep 14;75(5):786-794. doi: 10.1093/cid/ciab1065.

  PMID: 34996113 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

GSK3640254

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This will be a double blind study. Subjects and investigator will be blinded.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Eligible subjects will be randomized to receive two active doses of GSK3640254 along with placebo in Part 1 of the study. In Part 2, subjects will receive three active doses of GSK3640254 along with placebo depending upon the data obtained in Part 1.

Study Record Dates

• First Submitted: December 19, 2018
• First Posted: December 21, 2018
• Study Start: January 31, 2019
• Primary Completion: February 6, 2020
• Study Completion: February 6, 2020
• Last Updated: February 16, 2021
• Results First Posted: February 16, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (2); ES (10); ZA (3); DE (2); IT (3); FR (3)