Study to Evaluate the Effect of GBT440 on TCD in Pediatrics With Sickle Cell Disease
- Registration Number
- NCT04218084
- Lead Sponsor
- Pfizer
- Brief Summary
This study is a Phase 3, randomized, double-blind, placebo-controlled study of voxelotor in pediatric participants, aged ≥ 2 to \< 15 years old, with Sickle Cell Disease. The primary objective is to evaluate the effect of voxelotor on the TCD (Transcranial Doppler Ultrasound) measurements in SCD participants in this age range.
- Detailed Description
This study is a Phase 3, randomized, double-blind, placebo-controlled study of voxelotor in pediatric participants, aged ≥ 2 to \< 15 years old, with Sickle Cell Disease. The study will be conducted at approximately 50 international clinical sites, and will enroll approximately 224 participants. Participants will be randomized in a 1:1 ratio to receive voxelotor or placebo. All participants younger than 12 years of age and randomized to voxelotor will receive a dose based on their body weight, to provide exposure corresponding to the adult dose of 1500 mg/day.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 236
- Male or female participants with Sickle Cell Anemia (SCA) HbSS, HbSβ0 thalassemia genotype
- TCD time averaged maximum of the mean velocity (TAMMV) arterial cerebral blood flow ≥ 170 to 200cm/sec during the Screening Period
- Hb ≥ 5.5 and ≤ 10.5 g/dL during screening
- For participants taking HU, the dose of HU (mg/kg) must be stable for at least 90 days prior to signing the informed consent form (ICF) and/or assent form, and with no anticipated need for dose adjustments (other than weight based) or for initiation of HU for non-chronic use during the study, in the opinion of the Investigator
- Written informed parental/guardian consent and participant assent (where applicable) has been obtained per IRB/EC policy and requirements, consistent with ICH guidelines.
- Body weight < 10kg at the screening visit
- Hospitalization for VOC or acute chest syndrome (ACS) within the 14 days prior to execution of informed consent/assent
- More than 10 VOCs within the past 12 months that required hospitalization, emergency room, or clinic visit
- Stroke resulting in focal neurological deficit; previous silent infarcts are permitted.
- Known history or findings suggestive of significant cerebral vasculopathy
- History of seizure disorder
- Has been treated with erythropoietin or other hematopoietic growth factors within 28 days of signing informed consent/assent or if, in the opinion of the Investigator, there is an anticipated need for such agents during the study
- RBC transfusion therapy (also termed chronic, prophylactic, or preventative transfusion) or has received an RBC transfusion or exchange transfusion for any reason within 90 days of signing the informed consent/assent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Matching placebo. Voxelotor Voxelotor Voxelotor 1500mg or equivalent daily as a tablet, dispersible tablet, or as powder for oral suspension.
- Primary Outcome Measures
Name Time Method TCD Measurement 24 weeks The change in time averaged maximum of the mean velocity (TAMMV) arterial cerebral blood flow, as measured by TCD.
- Secondary Outcome Measures
Name Time Method TCD Flow Velocity Reduction 24, 48, and 96 weeks Proportion of participants with TCD flow velocity reduction ≥ 15 cm/sec
Change in Unconjugated Bilirubin from baseline baseline, 24, 48 and 96 weeks Change in TCD Flow Velocity 48 and 96 weeks Change in Percent of Reticulocyte from baseline baseline, 24, 48, and 96 weeks Time to Conversion to Abnormal TCD Flow Velocity 24, 48, and 96 weeks Time to conversion to abnormal TCD flow velocity (≥ 200 cm/sec)
Time to Reversion to Normal TCD Flow Velocity 24, 48, and 96 weeks Time to reversion to normal TCD flow velocity (\<170 cm/sec)
Number of Participants with Change in Hemoglobin (Hb) from baseline baseline, 24, 48, and 96 weeks Change in Absolute Reticulocyte from baseline baseline, 24, 48, and 96 weeks Change in Lactate Dehydrogenase (LDH) from baseline baseline, 24, 48, and 96 weeks Annualized incidence rate of vaso-occlusive crises (VOCs) 96 weeks
Trial Locations
- Locations (52)
Cairo University Hospital, Abu El Rish Hospital
🇪🇬Cairo, Egypt
Abu Elrish Children Hospital
🇪🇬Cairo, Egypt
Egyptian Thalassemia Association (satellite site)
🇪🇬Cairo, Egypt
Children's of Alabama
🇺🇸Birmingham, Alabama, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
University of Miami
🇺🇸Miami, Florida, United States
Children's Healthcare of Atlanta: Hughes Spalding
🇺🇸Atlanta, Georgia, United States
Children's Healthcare of Atlanta AFLAC Center
🇺🇸Atlanta, Georgia, United States
Children's Healthcare of Atlanta: Scottish Rite
🇺🇸Atlanta, Georgia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
Boston Childien's Hospital - Clinical Research Pharmacy
🇺🇸Boston, Massachusetts, United States
Boston Children's Hospital - Clinical Research Pharmacy
🇺🇸Boston, Massachusetts, United States
Boston Children's Hospital
🇺🇸Boston, Massachusetts, United States
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Medical University of South Carolina: Investigational Drug Services
🇺🇸Charleston, South Carolina, United States
Medical University of South Carolina: Shawn Jenkins Women's and Children's Hospital
🇺🇸Charleston, South Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
St. Jude Children's Research Hospital - Pharmaceutical Services
🇺🇸Memphis, Tennessee, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Texas Children's Hospital - Investigational Pharmacy
🇺🇸Houston, Texas, United States
Texas Children's Hospital- Wallace Tower
🇺🇸Houston, Texas, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Ain Shams University Hospital- Clinical Research Center (MASRI)
🇪🇬Cairo, Abassia, Egypt
Zagazig University Hospital
🇪🇬Zagazig, Alsharkia, Egypt
Alexandria Clinical Research Center, Faculty of Medicine, Alexandria University
🇪🇬Alexandria, Egypt
Abu El Rich Hospital, Cairo University Hospital
🇪🇬Cairo, Egypt
AP-HP Hopital Robert Debré
🇫🇷Paris, France
Komfo Anokye Teaching Hospital
🇬🇭Kumasi, Ashanti, Ghana
Department of Child Health, University of Ghana Medical School, College of Health Sciences, Korle-Bu
🇬🇭Accra, Greater Accra, Ghana
Azienda Ospedaliera Universitaria Meyer "A.O.U. Meyer" - SOC "Oncologia, Ematologia e TCSE"
🇮🇹Firenze, Italy
Azienda Ospedaliera Universitaria (A.O.U.) "Luigi Vanvitelli"
🇮🇹Napoli, Italy
Azienda Ospedaliera Universita' (AOU ) Padova
🇮🇹Padova, Italy
Azienda Ospedaliera Universita' (AOU) Padova
🇮🇹Padova, Italy
Kemri/Crdr,Siaya,Kemri Clinical Research Annex
🇰🇪Kisumu, Siaya, Kenya
KEMRI CRDR Clinical Research Annex
🇰🇪Nairobi, Kenya
Strathmore University Medical Centre
🇰🇪Nairobi, Kenya
Gertrude's Children Hospital
🇰🇪Nairobi, Kenya
Lagos University Teaching Hospital
🇳🇬Surulere, Lagos, Nigeria
College of Medicine, University of Ibadan
🇳🇬Ibadan, OYO State, Nigeria
University of Nigeria Teaching Hospital
🇳🇬Enugu, Nigeria
Barau Dikko Teaching/Kaduna State University
🇳🇬Kaduna, Nigeria
Aminu Kano Teaching Hospital
🇳🇬Kano, Nigeria
Sultan Qaboos University Hospital
🇴🇲Muscat, Oman
Sultan َQaboos University Hospital
🇴🇲Muscat, Oman
King Saud University Medical City
🇸🇦Riyadh, Saudi Arabia
King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard - Health
🇸🇦Riyadh, Saudi Arabia
Barts Health NHS Trust
🇬🇧London, United Kingdom
King's College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom