TERMINATED

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

Conditions

Hematologic Diseases Anaemia, Sickle Cell Sickle cell disease First time in human study 218471

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Randomized, Placebo-controlled, Double-Blind (Sponsor Unblind), Parallel Group, Single Dose, Dose Escalation Phase I Study in Sickle Cell Disease Participants, to Evaluate the Safety, Tolerability, and Pharmacokinetics of GSK4172239D

Quick Facts

Study Start:2023-08-26

Study Completion:2025-09-22

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:TERMINATED

Study ID

NCT05660265

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 50 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT

Inclusion Criteria	Exclusion Criteria
* 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.	* 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.

Inclusion Criteria

Exclusion Criteria

* 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.

* 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.

Contacts and Locations

Principal Investigator

GSK Clinical Trials

STUDY_DIRECTOR

GlaxoSmithKline

Study Locations (Sites)

GSK Investigational Site

Miami, Florida, 33155

United States

GSK Investigational Site

Tamarac, Florida, 33321

United States

GSK Investigational Site

Atlanta, Georgia, 30315

United States

GSK Investigational Site

Columbus, Georgia, 31904

United States

GSK Investigational Site

Riverdale, Georgia, 30274

United States

GSK Investigational Site

Las Vegas, Nevada, 89113

United States

Collaborators and Investigators

Sponsor: GlaxoSmithKline

GSK Clinical Trials, STUDY_DIRECTOR, GlaxoSmithKline

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-08-26

Study Completion Date2025-09-22

Study Record Updates

Study Start Date2023-08-26

Study Completion Date2025-09-22

Terms related to this study

Keywords Provided by Researchers

Hematologic diseases
Sickle cell disease
First time in human study
218471

Additional Relevant MeSH Terms

Hematologic Diseases
Anaemia, Sickle Cell