A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Oral GSK4172239D Compared With Placebo in Sickle Cell Disease Participants Aged 18 to 50 Years

NCT05660265 | Terminated Phase 1 FDA Drug

• 1 other identifier: 218471
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 6

Brief Summary

This will be a first time in human (FTIH) study in sickle cell diseases (SCD) participants. The FTIH study is planned to evaluate the safety, tolerability, and pharmacokinetics of GSK4172239D. The study will be composed of 3 periods for all participants (Screening, Treatment, and Follow up). Participants will be screened and, prior to first dose on Day 1, will be randomized to receive either GSK4172239D or placebo. GSK4172239D is a prodrug that is converted in vivo into GSK4106401. This study will be a single dose, dose-escalation study. The initial dosing for all cohorts will be staggered so that 2 participants will be dosed as sentinel participants. Provided there are no safety concerns in 48 hours (h), the remaining 6 participants scheduled for the cohort may be dosed. One selected cohort of participants will also receive an additional single dose of GSK4172239D (or matching placebo) under fed (high calorie and high fat) conditions after a washout period of a minimum of 20 days or 5 half-lives, whichever is longer, designated as the Food Effect Cohort.

Conditions

Hematologic Diseases; Anaemia, Sickle Cell

Keywords

Hematologic diseases; Sickle cell disease; First time in human study; 218471

Outcome Measures

Primary Outcomes (6)

• Area under curve zero to time infinity (AUC 0-inf) for GSK4106401 after a single oral dose of GSK4172239D

  Up to Day 3

• Maximum observed plasma concentration (Cmax) for GSK4106401 after a single oral dose of GSK4172239D

  Up to Day 3

• Time to Cmax (Tmax) for GSK4106401 after a single oral dose of GSK4172239D

  Up to Day 3

• Half-life (t1/2) for GSK4106401 after a single oral dose of GSK4172239D

  Up to Day 3

• Ratio between the fed and fasted conditions for AUC (0-inf)

  Up to Day 3

• Ratio between the fed and fasted conditions for Cmax

  Up to Day 3

Secondary Outcomes (10)

• Number of participants with clinically significant changes from baseline in white blood cell (WBC)

  Baseline and up to Day 7

• Number of participants with clinically significant changes from baseline in hemoglobin

  Baseline and up to Day 7

• Number of participants with clinically significant changes from baseline in platelets count

  Baseline and up to Day 7

• Number of participants with clinically significant changes from baseline in neutrophil count

  Baseline and up to Day 7

• Number of participants with clinically significant changes from baseline in alanine transaminase (ALT)

  Baseline and up to Day 7

Study Arms (6)

Cohort 1

EXPERIMENTAL

Participants in this arm will receive either single dose of GSK4172239D (Dose 1) or matching placebo.

Drug: GSK4172239D; Other: Placebo

Cohort 2

EXPERIMENTAL

Participants in this arm will receive either single dose of GSK4172239D (Dose 2) or matching placebo.

Drug: GSK4172239D; Other: Placebo

Cohort 3

EXPERIMENTAL

Participants in this arm will receive either single dose of GSK4172239D (Dose 3) or matching placebo.

Drug: GSK4172239D; Other: Placebo

Cohort 4

EXPERIMENTAL

Participants in this arm will receive either single dose of GSK4172239D (Dose 4) or matching placebo.

Drug: GSK4172239D; Other: Placebo

Cohort 5

EXPERIMENTAL

Participants in this arm will receive either single dose of GSK4172239D (Dose 5) or matching placebo.

Drug: GSK4172239D; Other: Placebo

Food effect cohort

EXPERIMENTAL

One selected cohort will also receive an additional single dose of GSK4172239D (or matching placebo) under fed (high calorie and high fat) conditions.

Drug: GSK4172239D; Other: Placebo

Interventions

Placebo OTHER

Matching placebo will be administered.

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Food effect cohort

GSK4172239D DRUG

Different strength of GSK4172239D will be administered in different cohorts.

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Food effect cohort

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants diagnosed with SCD not taking medication which increases gamma-globin (fetal hemoglobin).
• Participants with SCD who have failed or not tolerated one or more approved therapies for SCD
• Body weight greater than (\>) 50 kilogram (kg).
• For male participants: Refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent. OR agree to use a male condom with female partner. Agree to use an additional highly effective contraceptive method with a failure rate of less than (\<) 1% per year when having sexual intercourse with a woman of childbearing potential who is not currently pregnant
• For female participants: Female participants are eligible to participate if they are a woman of non-childbearing potential (WONCBP).
• Capable of giving informed consent.

You may not qualify if:

• Presence of active, clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study drug; or interfering with the interpretation of data.
• Clinically significant abnormal blood pressure and/or history of hypertension as determined by the investigator.
• History of clinically significant heart disease as determined by the investigator.
• Estimated glomerular filtration rate (eGFR) \< 60 ml/min/1.73m\^2
• ALT \> 3x upper limit of normal (ULN).
• Bilirubin \> 5x ULN (isolated bilirubin \> 5x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Hemoglobin \< 6 gram/decalitre (g/dL).
• Absolute neutrophil count \<1,500 / microlitre (μL).
• Platelet count \<75,000 /μL or \>750,000 /μL.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 t1/2 (whichever is longer) prior to the first dose of study drug, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise participant safety. By exception, participant may take acetaminophen (less than or equal to \[≤\] 2 g/day) up to 48h prior to the first dose of study drug.
• Use of hydroxyurea or decitabine within 9 weeks prior to baseline through follow-up.
• Blood transfusion within 3 months prior to baseline through follow-up.
• 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 drug or any other type of medical research.
• Positive pre-study drug/alcohol screen. By exception, opioid use for pain or benzodiazepine use for anxiety as directed by a physician is permitted.
• Regular use of known drugs of abuse, except for use directed by a physician. By exception, opioid use for pain or benzodiazepine use for anxiety is permitted.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (6)

GSK Investigational Site

Miami, Florida, 33155, United States

Location

GSK Investigational Site

Tamarac, Florida, 33321, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30315, United States

Location

GSK Investigational Site

Columbus, Georgia, 31904, United States

Location

GSK Investigational Site

Riverdale, Georgia, 30274, United States

Location

GSK Investigational Site

Las Vegas, Nevada, 89113, United States

Location

MeSH Terms

Conditions

Hematologic Diseases; Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This study will be a double blinded study where the sponsor may be unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a placebo controlled multi-center study.

Study Record Dates

• First Submitted: December 13, 2022
• First Posted: December 21, 2022
• Study Start: August 26, 2023
• Primary Completion: September 22, 2025
• Study Completion: September 22, 2025
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.

Locations

US (6)