Study to Evaluate the Effect of GBT440 in Pediatrics With Sickle Cell Disease

Sickle Cell Disease Clinical Trial

— HOPE  

Official title:

A Phase 2a, Open-label, Single and Multiple Dose Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Treatment Effect of GBT440 in Pediatric Participants With Sickle Cell Disease

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02850406
• Other study ID #: GBT440-007
• Secondary ID: C5341020
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 5, 2016
• Est. completion date: December 20, 2026

Study information

• Verified date: May 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study consists of four parts, Parts A, B, C, and D.

• Part A is a single dose pharmacokinetic (PK) study in pediatric participants with Sickle Cell Disease ages 6 to 17 years.

• Part B is a multiple dose, safety, exploratory, efficacy, and PK study in adolescent participants with Sickle Cell Disease ages 12 to 17 years.

• Part C is a multiple dose, safety, tolerability, and PK study, which includes the assessment of hematological effects and the effect on TCD flow velocity of voxelotor in pediatric participants with Sickle Cell Disease ages 4 to 17 years.

• Part D is a multiple dose, safety, tolerability, and PK study, which examines the hematological effects of voxelotor in pediatric participants with Sickle Cell Disease ages 6 months to < 4 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 147
• Est. completion date: December 20, 2026
• Est. primary completion date: November 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 17 Years

Eligibility

Inclusion Criteria:

• Male or female participants with homozygous hemoglobin SS (HbSS) or hemoglobin S beta0 thalassemia (HbS ß0thal)

• Age:

• Part A - 6 to 17 years of age

• Part B - 12 to 17 years of age

• Part C - 4 to 17 years of age

• Part D - 6 months to <4 years of age

• Hydroxyurea (HU) therapy:

• Parts A, B, and C: A participant taking hydroxyurea (HU) may be enrolled if the dose has been stable for at least 3 months with no anticipated need for dose adjustment during the study and no sign of hematological toxicity.

• Part D: A participant taking HU may be enrolled if the dose has been stable for at least 1 month. Titration to the maximum tolerated dose (MTD) is allowed during the study.

• Hemoglobin (HB):

• Part A - No restriction

• Parts B, C, & D - Hb = 10.5 g/dL

• For Part C only: Participants 12 to 17 years of age must have a TCD velocity of = 140 cm/sec measured anytime during screening.

Exclusion Criteria:

• Any one of the following requiring medical attention within 14 days of signing the Informed Consent Form (ICF):

• Vaso-occlusive crisis (VOC)

• Acute chest syndrome (ACS)

• Splenic sequestration crisis

• Dactylitis

• Requires chronic transfusion therapy

• History of stroke or meeting criteria for primary stroke prophylaxis (history of two TCD measurements = 200 cm/sec by non-imaging TCD or =185 cm/sec by TCDi).

• Transfusion within 30 days prior to signing the ICF

Exclusion Criteria for Part D Only:

• Body weight <5 kg for 1 month prior to the screening visit and at the screening visit.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• Voxelotor
Part A: Voxelotor will be administered as oral capsules or tablets Part B: Voxelotor will be administered as oral capsules or tablets Part C: Voxelotor will be administered as oral dispersible tablets or powder for oral suspension Part D: Voxelotor will be administered as oral dispersible tablets or powder for oral suspension

Locations

Country	Name	City	State
Lebanon	American University of Beirut - Medical Center	Beirut
Lebanon	Rafik Hariri University Hospital	Beirut
Lebanon	Nini Hospital	Tripoli
United Kingdom	Barts Health NHS Trust, The Royal London Hospital	London
United Kingdom	Guy's and St Thoma's NHS Foundation Trust, Evelina London Children's Hospital	London
United Kingdom	University College London Hospital, NHS Foundation Trust	London	Greater London
United Kingdom	Manchester University NHS Foundation Trust, Royal Manchester Children's Hospital	Manchester
United States	Children's Healthcare of Atlanta Scottish Rite	Atlanta	Georgia
United States	Emory Children's Center	Atlanta	Georgia
United States	Our Lady of the Lake Children's Hospital (IP Address)	Baton Rouge	Louisiana
United States	St. Jude Affiliate Clinic at Our Lady of the Lake Children's Health	Baton Rouge	Louisiana
United States	Brentwood Clinic UCSF Benioff Children's Hospital Oakland	Brentwood	California
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	University of Illinois at Chicago Clinical Research Center	Chicago	Illinois
United States	University of Illinois Hospital and Health Sciences System	Chicago	Illinois
United States	University Hospitals Cleveland Medical Center, Rainbow Babies & Children's Hospital	Cleveland	Ohio
United States	Brody School of Medicine at East Carolina University	Greenville	North Carolina
United States	ECU Physicians	Greenville	North Carolina
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	St. Jude Children's Research Hospital - Pharmaceutical Services	Memphis	Tennessee
United States	Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Rutgers-Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Rutgers-Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	UCSF Benioff Children's Hospital Walnut Creek	Walnut Creek	California
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Lebanon,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Pharmacokinetic profile of voxelotor including maximum concentration	Maximum observed concentration (Cmax), area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last), and area under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of voxelotor in whole blood	Pre-dose to Day 15
Primary	Part A: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration	Maximum observed concentration (Cmax), area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last), and area under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of voxelotor in whole blood	Pre-dose to Day 15
Primary	Part A: Pharmacokinetic profile of voxelotor including the total drug concentration over time	Maximum observed concentration (Cmax), area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last), and area under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of voxelotor in whole blood	Pre-dose to Day 15
Primary	Part B: Change in hemoglobin	Change from baseline to Week 24 in Hb	Baseline to Week 24
Primary	Part C: Change in cerebral blood flow as measured by the TAMM TCD velocity	Change from baseline to 12 and 24 weeks in cerebral blood flow as measured by the time-averaged mean of the maximum (TAMM) TCD velocity	Baseline to Week 48
Primary	Part D: Treatment-Emergent Adverse Events and Serious Adverse Events	Participants will be monitored throughout the study for AEs, from the time informed consent is obtained through the EOS visit. The Investigator will assess each AE for seriousness, intensity and relationship to investigational product.	Baseline to Week 48
Secondary	Part A: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03		Days 1 - 15
Secondary	Part B: Multiple Dose effect on Clinical Measures of Hemolysis		Day 1 - Week 24
Secondary	Part B: Pharmacokinetic profile of voxelotor including maximum concentration		Pre-dose to Week 24
Secondary	Part B: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration		Pre-dose to Week 24
Secondary	Part B: Pharmacokinetic profile of voxelotor including the total drug concentration over time		Pre-dose to Week 24
Secondary	Part C: Multiple dose effect on clinical measures of hemolysis		Baseline to Week 24 and Week 48
Secondary	Part C: Change in cerebral blood flow as measured by TAMM TCD velocity		Baseline to Week 24
Secondary	Part C: Time to initial Hemoglobin response	Change from baseline in Hb > 1g/dL	Baseline to Week 48
Secondary	Part C: Pharmacokinetic profile of voxelotor including percent Hemoglobin occupancy		Baseline to Week 48
Secondary	Part C: Proportion of participants with normal TCD flow velocity		Baseline to Week 48
Secondary	Part C: Incidence of stroke and VOC		Baseline to Week 48
Secondary	Part D: Pharmacokinetic profile of voxelotor including percent Hemoglobin occupancy		Baseline to Week 48
Secondary	Part D: Change in Hemoglobin		Baseline to Week 24 and Week 48
Secondary	Part D: Change in Lactate Dehydrogenase		Baseline to Week 24 and Week 48
Secondary	Part D: Change in Indirect Bilirubin		Baseline to Week 24 and Week 48
Secondary	Part D: Change in Reticulocyte Count		Baseline to Week 24 and Week 48
Secondary	Part D: Time to initial Hemoglobin response	Change from baseline in Hb > 1g/dL	Baseline to Week 48
Secondary	Part D: Incidence of stroke and VOC		Baseline to Week 48

External Links

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