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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

Primary Purpose

Hematologic Diseases, Anaemia, Sickle Cell

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GSK4172239D
Placebo
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematologic Diseases focused on measuring Hematologic diseases, Sickle cell disease, First time in human study, 218471

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion 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. Exclusion Criteria: 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.

Sites / Locations

  • GSK Investigational SiteRecruiting
  • GSK Investigational SiteRecruiting
  • GSK Investigational SiteRecruiting
  • GSK Investigational SiteRecruiting
  • GSK Investigational SiteRecruiting
  • GSK Investigational SiteRecruiting
  • GSK Investigational SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Cohort 5

Food effect cohort

Arm Description

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

Area under curve zero to time infinity (AUC 0-inf) for GSK4106401 after a single oral dose of GSK4172239D
Maximum observed plasma concentration (Cmax) for GSK4106401 after a single oral dose of GSK4172239D
Time to Cmax (Tmax) for GSK4106401 after a single oral dose of GSK4172239D
Half-life (t1/2) for GSK4106401 after a single oral dose of GSK4172239D
Ratio between the fed and fasted conditions for AUC (0-inf)
Ratio between the fed and fasted conditions for Cmax

Secondary Outcome Measures

Number of participants with clinically significant changes from baseline in white blood cell (WBC)
Number of participants with clinically significant changes from baseline in hemoglobin
Number of participants with clinically significant changes from baseline in platelets count
Number of participants with clinically significant changes from baseline in neutrophil count
Number of participants with clinically significant changes from baseline in alanine transaminase (ALT)
Number of participants with clinically significant changes from baseline in aspartate transaminase (AST)
Number of participants with clinically significant changes from baseline in bilirubin
Number of participants with adverse event (AE) and serious adverse event (SAE)
Number of participants with clinically significant change from baseline in 12 lead electrocardiograms (ECG)
Number of participants with clinically significant change from baseline in vital signs

Full Information

First Posted
December 13, 2022
Last Updated
September 7, 2023
Sponsor
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT05660265
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 26, 2023 (Actual)
Primary Completion Date
May 19, 2025 (Anticipated)
Study Completion Date
May 19, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Diseases, Anaemia, Sickle Cell
Keywords
Hematologic diseases, Sickle cell disease, First time in human study, 218471

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
This is a placebo controlled multi-center study.
Masking
ParticipantCare ProviderInvestigator
Masking Description
This study will be a double blinded study where the sponsor may be unblinded.
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Participants in this arm will receive either single dose of GSK4172239D (Dose 1) or matching placebo.
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Participants in this arm will receive either single dose of GSK4172239D (Dose 2) or matching placebo.
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
Participants in this arm will receive either single dose of GSK4172239D (Dose 3) or matching placebo.
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
Participants in this arm will receive either single dose of GSK4172239D (Dose 4) or matching placebo.
Arm Title
Cohort 5
Arm Type
Experimental
Arm Description
Participants in this arm will receive either single dose of GSK4172239D (Dose 5) or matching placebo.
Arm Title
Food effect cohort
Arm Type
Experimental
Arm Description
One selected cohort will also receive an additional single dose of GSK4172239D (or matching placebo) under fed (high calorie and high fat) conditions.
Intervention Type
Drug
Intervention Name(s)
GSK4172239D
Intervention Description
Different strength of GSK4172239D will be administered in different cohorts.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Matching placebo will be administered.
Primary Outcome Measure Information:
Title
Area under curve zero to time infinity (AUC 0-inf) for GSK4106401 after a single oral dose of GSK4172239D
Time Frame
Up to Day 3
Title
Maximum observed plasma concentration (Cmax) for GSK4106401 after a single oral dose of GSK4172239D
Time Frame
Up to Day 3
Title
Time to Cmax (Tmax) for GSK4106401 after a single oral dose of GSK4172239D
Time Frame
Up to Day 3
Title
Half-life (t1/2) for GSK4106401 after a single oral dose of GSK4172239D
Time Frame
Up to Day 3
Title
Ratio between the fed and fasted conditions for AUC (0-inf)
Time Frame
Up to Day 3
Title
Ratio between the fed and fasted conditions for Cmax
Time Frame
Up to Day 3
Secondary Outcome Measure Information:
Title
Number of participants with clinically significant changes from baseline in white blood cell (WBC)
Time Frame
Baseline and up to Day 7
Title
Number of participants with clinically significant changes from baseline in hemoglobin
Time Frame
Baseline and up to Day 7
Title
Number of participants with clinically significant changes from baseline in platelets count
Time Frame
Baseline and up to Day 7
Title
Number of participants with clinically significant changes from baseline in neutrophil count
Time Frame
Baseline and up to Day 7
Title
Number of participants with clinically significant changes from baseline in alanine transaminase (ALT)
Time Frame
Baseline and up to Day 7
Title
Number of participants with clinically significant changes from baseline in aspartate transaminase (AST)
Time Frame
Baseline and up to Day 7
Title
Number of participants with clinically significant changes from baseline in bilirubin
Time Frame
Baseline and up to Day 7
Title
Number of participants with adverse event (AE) and serious adverse event (SAE)
Time Frame
Up to Day 7
Title
Number of participants with clinically significant change from baseline in 12 lead electrocardiograms (ECG)
Time Frame
Baseline and up to Day 7
Title
Number of participants with clinically significant change from baseline in vital signs
Time Frame
Baseline and up to Day 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name or Official Title & Degree
EU GSK Clinical Trials Call Center
Phone
+44 (0) 20 89904466
Email
GSKClinicalSupportHD@gsk.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
Mary Sehl
Facility Name
GSK Investigational Site
City
Tamarac
State/Province
Florida
ZIP/Postal Code
33321
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
Mazyar Rouhani
Facility Name
GSK Investigational Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30315
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com
Facility Name
GSK Investigational Site
City
Douglasville
State/Province
Georgia
ZIP/Postal Code
30134
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com
Facility Name
GSK Investigational Site
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89113
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com
Facility Name
GSK Investigational Site
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
Darla K Liles
Facility Name
GSK Investigational Site
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27617
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
US GSK Clinical Trials Call Center
Phone
877-379-3718
Email
GSKClinicalSupportHD@gsk.com
First Name & Middle Initial & Last Name & Degree
EU GSK Clinical Trials Call Centre
Phone
+44 (0) 20 8990 4466
Email
GSKClinicalSupportHD@gsk.com

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Learn more about this trial

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

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