A Study to Evaluate GBT021601-012 Single Dose and Multiple Dose in Participants With Sickle Cell Disease (SCD)
Study Details
Study Description
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 |
---|---|---|
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.
Study Design
Arms and Interventions
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
|
Outcome Measures
Primary Outcome Measures
- Safety, as assessed by frequency and severity of adverse events (AEs) [31 weeks]
AEs will be coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA) and summarized.
- Safety, as assessed by changes in Heart Rate [31 weeks]
Number of participants with changes in heart rate (bpm) as compared to baseline
- Safety, as assessed by changes in QTcF [31 weeks]
Number of participants with changes in the QTcF interval from baseline
- Safety, as assessed by changes in eGFR [31 weeks]
Number of participants with changes in eGFR from baseline
- Safety, as assessed by changes in alanine aminotransferase (ALT) [31 weeks]
Number of participants with changes in alanine aminotransferase (ALT)
- Safety, as assessed by changes in Blood pressure [31 weeks]
Number of participants with changes in systolic (mmHg) and diastolic (mmHg) blood pressure from baseline
Secondary Outcome Measures
- Determine plasma and whole blood concentrations of GBT021601 and calculate RBC concentrations. [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.
- Determine the pharmacodynamic effect of GBT021601 treatment. [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.
- 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. [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).
Eligibility Criteria
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
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Patients on HU should be on stable dose for at least 90 days prior to signing ICF
Exclusion Criteria:
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Patients had more than 10 VOC within 12 months of screening
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Patients who are pregnant or nursing
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Patients who receive RBC transfusion therapy regularly or received an RBC transfusion for any reason within 60 days of signing the ICF
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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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Visionaries Clinical Research | Atlanta | Georgia | United States | 30329 |
2 | Children's Healthcare of Atlanta | Atlanta | Georgia | United States | 30342 |
Sponsors and Collaborators
- Global Blood Therapeutics
Investigators
- Study Director: Eleanor Lisbon, MD, MPH, Global Blood Therapeutics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GBT021601-012