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

Primary Purpose

Sickle Cell Disease

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GBT021601
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Advanced Pharma CR, LLC
  • Visionaries Clinical Research LLC
  • Children's Healthcare of Atlanta AFLAC Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Single-dose Period (Part A)

Multiple Ascending-dose Period (Part B and Part C)

Arm Description

Refer to Study Description

Refer to Study Description

Outcomes

Primary Outcome Measures

Safety, as assessed by frequency and severity of adverse events (AEs)
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
Number of participants with changes in heart rate (bpm) as compared to baseline
Safety, as assessed by changes in QTcF
Number of participants with changes in the QTcF interval from baseline
Safety, as assessed by changes in eGFR
Number of participants with changes in eGFR from baseline
Safety, as assessed by changes in alanine aminotransferase (ALT)
Number of participants with changes in alanine aminotransferase (ALT)
Safety, as assessed by changes in Blood pressure
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.
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.
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.
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).

Full Information

First Posted
May 27, 2021
Last Updated
September 7, 2023
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT04983264
Brief Title
A Study to Evaluate GBT021601-012 Single Dose and Multiple Dose in Participants With Sickle Cell Disease (SCD)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
May 28, 2021 (Actual)
Primary Completion Date
December 6, 2022 (Actual)
Study Completion Date
December 6, 2022 (Actual)

3. Sponsor/Collaborators

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

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
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single-dose Period (Part A)
Arm Type
Experimental
Arm Description
Refer to Study Description
Arm Title
Multiple Ascending-dose Period (Part B and Part C)
Arm Type
Experimental
Arm Description
Refer to Study Description
Intervention Type
Drug
Intervention Name(s)
GBT021601
Intervention Description
Tablets and capsules which contain GBT021601 drug substance
Primary Outcome Measure Information:
Title
Safety, as assessed by frequency and severity of adverse events (AEs)
Description
AEs will be coded to system organ class and preferred term using the Medical Dictionary for Regulatory Activities (MedDRA) and summarized.
Time Frame
31 weeks
Title
Safety, as assessed by changes in Heart Rate
Description
Number of participants with changes in heart rate (bpm) as compared to baseline
Time Frame
31 weeks
Title
Safety, as assessed by changes in QTcF
Description
Number of participants with changes in the QTcF interval from baseline
Time Frame
31 weeks
Title
Safety, as assessed by changes in eGFR
Description
Number of participants with changes in eGFR from baseline
Time Frame
31 weeks
Title
Safety, as assessed by changes in alanine aminotransferase (ALT)
Description
Number of participants with changes in alanine aminotransferase (ALT)
Time Frame
31 weeks
Title
Safety, as assessed by changes in Blood pressure
Description
Number of participants with changes in systolic (mmHg) and diastolic (mmHg) blood pressure from baseline
Time Frame
31 weeks
Secondary Outcome Measure Information:
Title
Determine plasma and whole blood concentrations of GBT021601 and calculate RBC concentrations.
Description
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.
Time Frame
31 weeks
Title
Determine the pharmacodynamic effect of GBT021601 treatment.
Description
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.
Time Frame
14 weeks
Title
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.
Description
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).
Time Frame
14 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Advanced Pharma CR, LLC
City
Miami
State/Province
Florida
ZIP/Postal Code
33147
Country
United States
Facility Name
Visionaries Clinical Research LLC
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Facility Name
Children's Healthcare of Atlanta AFLAC Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=GBT021601-012
Description
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Learn more about this trial

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

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