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A Study to Evaluate GBT021601-012 Single Dose and Multiple Dose in Participants With Sickle Cell Disease (SCD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04983264
Recruitment Status : Active, not recruiting
First Posted : July 30, 2021
Last Update Posted : August 12, 2022
Sponsor:
Information provided by (Responsible Party):
Global Blood Therapeutics

Brief Summary:
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK), and pharmacodynamics (i.e., how the body absorbs, distributes, breaks down, and excretes) of GBT021601, a hemoglobin S (HbS) polymerization inhibitor, in participants with SCD, following single and multiple ascending doses.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: GBT021601 Phase 1

Detailed Description:
This is an open-label intrapatient single dose followed by a multiple dose escalation study in at least six (6) participants with SCD.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Intrapatient Single Dose and Multiple Ascending Dose Study to Evaluate the Pharmacokinetics, Safety, Tolerability, and Pharmacodynamics of GBT021601, a Hemoglobin S Polymerization Inhibitor, in Participants With Sickle Cell Disease (SCD)
Actual Study Start Date : May 28, 2021
Estimated Primary Completion Date : October 31, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Single-dose Period (Part A)
Refer to Study Description
Drug: GBT021601
Tablets and capsules which contain GBT021601 drug substance

Experimental: Multiple Ascending-dose Period (Part B and Part C)
Refer to Study Description
Drug: GBT021601
Tablets and capsules which contain GBT021601 drug substance




Primary Outcome Measures :
  1. Safety, as assessed by frequency and severity of adverse events (AEs) [ Time Frame: 31 weeks ]
    AEs will be coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA) and summarized.

  2. Safety, as assessed by changes in Heart Rate [ Time Frame: 31 weeks ]
    Number of participants with changes in heart rate (bpm) as compared to baseline

  3. Safety, as assessed by changes in QTcF [ Time Frame: 31 weeks ]
    Number of participants with changes in the QTcF interval from baseline

  4. Safety, as assessed by changes in eGFR [ Time Frame: 31 weeks ]
    Number of participants with changes in eGFR from baseline

  5. Safety, as assessed by changes in alanine aminotransferase (ALT) [ Time Frame: 31 weeks ]
    Number of participants with changes in alanine aminotransferase (ALT)

  6. Safety, as assessed by changes in Blood pressure [ Time Frame: 31 weeks ]
    Number of participants with changes in systolic (mmHg) and diastolic (mmHg) blood pressure from baseline


Secondary Outcome Measures :
  1. Determine plasma and whole blood concentrations of GBT021601 and calculate RBC concentrations. [ Time Frame: 31 weeks ]
    Noncompartmental PK analysis or population PK analysis using nonlinear mixed-effect modeling will be performed to characterize GBT021601 PK in plasma, and whole blood following single and multiple doses.

  2. Determine the pharmacodynamic effect of GBT021601 treatment. [ Time Frame: 14 weeks ]
    Hemoximetry will be used to assess oxygen saturation in whole blood by generating oxygen equilibrium curves (OECs) which relate the extent of Hb-O2 saturation to the partial pressure of O2 (pO2) and measure the binding affinity of O2 to Hb. Red Blood Cell Deformability will be measured by an Osmoscan. Individual and mean PD marker data will be presented graphically.

  3. To confirm the the relationship between time-matched GBT021601 concentrations and the change from baseline or percentage change from baseline of clinical measures of anemia and hemolysis. [ Time Frame: 14 weeks ]
    To confirm the correlation between time-matched GBT021601 concentrations and the change from baseline or percentage change from baseline of clinical measures of anemia (hemoglobin) and hemolysis (including indirect bilirubin, reticulocytes and lactate dehydrogenase).



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or Female with SCD
  • Participants with SCD ages 18 to 60 years, inclusive.
  • Participant has provided documented informed consent.
  • Patients with stable and close to baseline hemoglobin value
  • Patients on HU should be on stable dose for at least 90 days prior to signing ICF

Exclusion Criteria:

  • Patients had more than 10 VOC within 12 months of screening
  • Patients who are pregnant or nursing
  • Patients who receive RBC transfusion therapy regularly or received an RBC transfusion for any reason within 60 days of signing the ICF
  • Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF or within 24 days prior to Day 1 treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04983264


Locations
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United States, Georgia
Visionaries Clinical Research
Atlanta, Georgia, United States, 30329
Children's Healthcare of Atlanta
Atlanta, Georgia, United States, 30342
Sponsors and Collaborators
Global Blood Therapeutics
Investigators
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Study Director: Eleanor Lisbon, MD, MPH Global Blood Therapeutics
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Responsible Party: Global Blood Therapeutics
ClinicalTrials.gov Identifier: NCT04983264    
Other Study ID Numbers: GBT021601-012
First Posted: July 30, 2021    Key Record Dates
Last Update Posted: August 12, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn