A Study in Adult and Pediatric Participants With Sickle Cell Disease (SCD)

• Sponsor: Global Blood Therapeutics (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05431088
• Collaborator: (none)
• Enrollment: 480
• Location: 1
• Arms: 3
• Anticipated Duration (Months): 55.7
• Patients Per Site Per Month: 8.6

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of GBT021601.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Drug: GBT021601	Phase 2/Phase 3

Detailed Description

This is a three-part, multicenter, Phase 2/3 study of orally administered GBT021601 in participants with sickle cell disease (SCD). Part A will evaluate the safety, tolerability, and efficacy of GBT021601 in adult participants with SCD to determine an optimal dose. Part B will evaluate the efficacy of GBT021601 versus placebo in adult and pediatric participants with SCD for 48 weeks. Part C will evaluate the pharmacokinetics (PK) and safety of single and multiple doses (MD) of open-label single arm GBT021601 administered to pediatric participants.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 480 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Part B only
• Primary Purpose: Treatment
• Official Title: A Phase 2/3 Randomized, Multicenter Study of GBT021601 Administered Orally to Participants With Sickle Cell Disease and an Open-Label Pharmacokinetics Study in Pediatric Participants With Sickle Cell Disease
• Anticipated Study Start Date: Aug 11, 2022
• Anticipated Primary Completion Date: Oct 1, 2026
• Anticipated Study Completion Date: Apr 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Part A Initially, participants will be randomized 1:1 to 100 mg and 150 mg daily. Upon review of the 150 mg safety data from at least 6 participants, there will be 1:1:1 randomization: 100 mg, 150 mg, and up to 200 mg. Participants will then receive maintenance once daily doses through Week 12.	Drug: GBT021601; Tablets which contain GBT021601 drug substance
Placebo Comparator: Part B Following the selection of the optimal safe and effective dose from Part A of the study, Part B of the study will assess the efficacy and safety of 48 weeks of the optimal dose, compared to placebo	Drug: GBT021601; Tablets which contain GBT021601 drug substance
Experimental: Part C 100 mg dose in cohort C1, dose level for cohorts C2 to C4 to be determined based on emerging data	Drug: GBT021601; Tablets which contain GBT021601 drug substance

Outcome Measures

Primary Outcome Measures

1. Part A [Through week 12]

   Number of adult participants with change from baseline in hemoglobin (Hb) through week 12 as measured by change in GBT021601 concentrations from baseline or percentage change from baseline of clinical measures of anemia (hemoglobin) and hemolysis (including indirect bilirubin, reticulocytes and lactate dehydrogenase).

2. Part B [Through week 48]

   Proportion of participants with an increase from baseline of >1 g/dL in Hb at week 48 as measured by change in GBT021601 concentrations from baseline or percentage change from baseline of clinical measures of anemia (hemoglobin) and hemolysis (including indirect bilirubin, reticulocytes and lactate dehydrogenase).

3. Part C [Through Week 6]

   Assess the pharmacokinetics, while observing maximum concentration (Cmax) after a single dose as measured by a noncompartmental PK analysis or population PK analysis using nonlinear mixed-effect modeling.

4. Part C [Through Week 2]

   Assess the pharmacokinetics, while observing minimum concentration (Cmin) and maximum concentration after multiple dose administration as measured by a 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 multiple doses.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Part A, Part B, and Part C:

• Male or female with SCD

• Participants with stable hemoglobin value

• Participants on HU should be on stable dose for at least 90 days prior to signing ICF

Part B:

• Participants with SCD ages 12 to 65 years, inclusive

• Participants with more than or equal to 2 and less than or equal to 10 VOCs inclusive, within 12 months of Screening

Exclusion Criteria:

Part A, Part B, and Part C:

• Participants who had more than 10 VOC within 12 months of screening

• Female participant who is breastfeeding or pregnant

• Participants who receive RBC transfusion therapy regularly or received an RBC transfusion ---for any reason within 90 days of Day 1

• Participants hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lynn Institute of the Ozarks	Little Rock	Arkansas	United States	72204

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.

• Responsible Party: Global Blood Therapeutics
• ClinicalTrials.gov Identifier: NCT05431088
• Other Study ID Numbers: GBT021601-021
• First Posted: Jun 24, 2022
• Last Update Posted: Aug 12, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Anemia, Sickle Cell

Study Results

No Results Posted as of Aug 12, 2022