Study to Evaluate the Effect of GBT440 in Pediatrics With Sickle Cell Disease
- Registration Number
- NCT02850406
- Lead Sponsor
- Pfizer
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 147
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Male or female participants with homozygous hemoglobin SS (HbSS) or hemoglobin S beta0 thalassemia (HbS β0thal)
-
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.
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Voxelotor Voxelotor Subjects to receive daily oral dosing of voxelotor according to which Part (A, B, C, or D), the subject is participating in: * Part A: Subjects to receive daily oral dosing of voxelotor for 1 day (single dose) * Part B: Subjects to receive daily oral dosing of voxelotor for up to 24 weeks (multiple dose) * Part C: Subjects to receive daily oral dosing of voxelotor for up to 48 weeks (1500mg or 1500mg equivalent dose) * Part D: Subjects to receive daily oral dosing of voxelotor for up to 48 weeks (1500mg equivalent dose)
- Primary Outcome Measures
Name Time Method Part A: Pharmacokinetic profile of voxelotor including maximum concentration Pre-dose to Day 15 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
Part A: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration Pre-dose to Day 15 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
Part A: Pharmacokinetic profile of voxelotor including the total drug concentration over time Pre-dose to Day 15 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
Part B: Change in hemoglobin Baseline to Week 24 Change from baseline to Week 24 in Hb
Part C: Change in cerebral blood flow as measured by the TAMM TCD velocity Baseline to Week 48 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
Part D: Treatment-Emergent Adverse Events and Serious Adverse Events Baseline to Week 48 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.
- Secondary Outcome Measures
Name Time Method Part C: Multiple dose effect on clinical measures of hemolysis Baseline to Week 24 and Week 48 Part C: Change in cerebral blood flow as measured by TAMM TCD velocity Baseline to Week 24 Part C: Time to initial Hemoglobin response Baseline to Week 48 Change from baseline in Hb \> 1g/dL
Part C: Proportion of participants with normal TCD flow velocity Baseline to Week 48 Part A: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 Days 1 - 15 Part B: Multiple Dose effect on Clinical Measures of Hemolysis Day 1 - Week 24 Part B: Pharmacokinetic profile of voxelotor including maximum concentration Pre-dose to Week 24 Part B: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration Pre-dose to Week 24 Part B: Pharmacokinetic profile of voxelotor including the total drug concentration over time Pre-dose to Week 24 Part C: Pharmacokinetic profile of voxelotor including percent Hemoglobin occupancy Baseline to Week 48 Part C: Incidence of stroke and VOC Baseline to Week 48 Part D: Pharmacokinetic profile of voxelotor including percent Hemoglobin occupancy Baseline to Week 48 Part D: Change in Hemoglobin Baseline to Week 24 and Week 48 Part D: Change in Lactate Dehydrogenase Baseline to Week 24 and Week 48 Part D: Change in Indirect Bilirubin Baseline to Week 24 and Week 48 Part D: Change in Reticulocyte Count Baseline to Week 24 and Week 48 Part D: Time to initial Hemoglobin response Baseline to Week 48 Change from baseline in Hb \> 1g/dL
Part D: Incidence of stroke and VOC Baseline to Week 48
Trial Locations
- Locations (28)
Our Lady of the Lake Children's Hospital (IP Address)
🇺🇸Baton Rouge, Louisiana, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
University of Illinois Hospital and Health Sciences System
🇺🇸Chicago, Illinois, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
St. Jude Affiliate Clinic at Our Lady of the Lake Children's Health
🇺🇸Baton Rouge, Louisiana, United States
UCSF Benioff Children's Hospital Oakland
🇺🇸Oakland, California, United States
Brentwood Clinic UCSF Benioff Children's Hospital Oakland
🇺🇸Brentwood, California, United States
American University of Beirut - Medical Center
🇱🇧Beirut, Lebanon
St. Jude Children's Research Hospital - Pharmaceutical Services
🇺🇸Memphis, Tennessee, United States
University of Illinois at Chicago Clinical Research Center
🇺🇸Chicago, Illinois, United States
Emory Children's Center
🇺🇸Atlanta, Georgia, United States
Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
Manchester University NHS Foundation Trust, Royal Manchester Children's Hospital
🇬🇧Manchester, United Kingdom
Nini Hospital
🇱🇧Tripoli, Lebanon
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Rafik Hariri University Hospital
🇱🇧Beirut, Lebanon
Barts Health NHS Trust, The Royal London Hospital
🇬🇧London, United Kingdom
University College London Hospital, NHS Foundation Trust
🇬🇧London, Greater London, United Kingdom
Guy's and St Thoma's NHS Foundation Trust, Evelina London Children's Hospital
🇬🇧London, United Kingdom
UCSF Benioff Children's Hospital Walnut Creek
🇺🇸Walnut Creek, California, United States
Brody School of Medicine at East Carolina University
🇺🇸Greenville, North Carolina, United States
Children's Healthcare of Atlanta Scottish Rite
🇺🇸Atlanta, Georgia, United States
University Hospitals Cleveland Medical Center, Rainbow Babies & Children's Hospital
🇺🇸Cleveland, Ohio, United States
Rutgers-Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
ECU Physicians
🇺🇸Greenville, North Carolina, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States