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

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)

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: GBT021601

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 Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33147
      • Advanced Pharma CR, LLC
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Children's Healthcare of Atlanta AFLAC Center
    • Atlanta, Georgia, United States, 30329
      • Visionaries Clinical Research LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	31 weeks
Safety, as assessed by changes in Heart Rate	Number of participants with changes in heart rate (bpm) as compared to baseline	31 weeks
Safety, as assessed by changes in QTcF	Number of participants with changes in the QTcF interval from baseline	31 weeks
Safety, as assessed by changes in eGFR	Number of participants with changes in eGFR from baseline	31 weeks
Safety, as assessed by changes in alanine aminotransferase (ALT)	Number of participants with changes in alanine aminotransferase (ALT)	31 weeks
Safety, as assessed by changes in Blood pressure	Number of participants with changes in systolic (mmHg) and diastolic (mmHg) blood pressure from baseline	31 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	31 weeks
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.	14 weeks
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).	14 weeks

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2021
• Primary Completion (Actual): December 6, 2022
• Study Completion (Actual): December 6, 2022

Study Registration Dates

• First Submitted: May 27, 2021
• First Submitted That Met QC Criteria: July 27, 2021
• First Posted (Actual): July 30, 2021

Study Record Updates

• Last Update Posted (Actual): September 11, 2023
• Last Update Submitted That Met QC Criteria: September 7, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: GBT021601-012; C5351002 (Other Identifier: Pfizer)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No