Clinical trial NCT04218084: Study to Evaluate the Effect of GBT440 on TCD in Pediatrics With Sickle Cell Disease
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Voxelotor (GBT440) in Pediatric Participants With Sickle Cell Disease (HOPE Kids 2)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Sickle Cell Disease
Keywords: Sickle Cell Disease
Transcranial Doppler Ultrasound (TCD)
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2020-01-06
Enrollment: 236
Sex: ALL
Minimum age (years): 2
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Male or female participants with Sickle Cell Anemia (SCA) HbSS, HbSβ0 thalassemia genotype
2. TCD time averaged maximum of the mean velocity (TAMMV) arterial cerebral blood flow ≥ 170 to \< 200cm/sec during the Screening Period
3. Hb ≥ 5.5 and ≤ 10.5 g/dL during screening
4. 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
5. Written informed parental/guardian consent and participant assent (where applicable) has been obtained per IRB/EC policy and requirements, consistent with ICH guidelines.

Exclusion Criteria:

1. Body weight \< 10kg at the screening visit
2. Hospitalization for VOC or acute chest syndrome (ACS) within the 14 days prior to execution of informed consent/assent
3. More than 10 VOCs within the past 12 months that required hospitalization, emergency room, or clinic visit
4. Stroke resulting in focal neurological deficit; previous silent infarcts are permitted.
5. Known history or findings suggestive of significant cerebral vasculopathy
6. History of seizure disorder
7. 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
8. 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

Primary outcomes:
measure: Change From Baseline in Time-Averaged Maximum of Mean Velocity (TAMMV) Arterial Cerebral Blood Flow at Week 24
timeFrame: Baseline (value at screening), Week 24
Secondary outcomes:
measure: Change From Baseline in Transcranial Doppler (TCD) Flow Velocity at Week 48.
timeFrame: From treatment initiation till study completion
measure: Time to Conversion to Abnormal TCD Flow
timeFrame: From treatment initiation till study completion
measure: Time to Reversion to Normal TCD Flow
timeFrame: From treatment initiation till study completion
measure: Percentage of Participants With TCD Flow Velocity Reduction Greater Than or Equal to (>=)15 cm/Sec at Weeks 24 and 48
timeFrame: From treatment initiation till study completion
measure: Change From Baseline in Hemoglobin (Hb) at Weeks 24 and 48
timeFrame: From treatment initiation till study completion
measure: Percent Change From Baseline in Unconjugated Bilirubin at Weeks 24 and 48
timeFrame: From treatment initiation till study completion
measure: Percent Change From Baseline in Reticulocyte at Weeks 24 and 48
timeFrame: From treatment initiation till study completion
measure: Percent Change From Baseline in Absolute Reticulocyte at Weeks 24 and 48
timeFrame: From treatment initiation till study completion
measure: Percent Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 24 and 48
timeFrame: From treatment initiation till study completion
measure: Annualized Incidence Rate of Vaso-Occlusive Crises (VOCs)
timeFrame: From treatment initiation till study completion
Other outcomes:
Locations:
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta: Hughes Spalding
state: Georgia
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Texas Children's Hospital- Wallace Tower
state: Texas
city: Alexandria
country: Egypt
facility: Alexandria Clinical Research Center, Faculty of Medicine, Alexandria University
city: Alexandria
country: Egypt
facility: Zagazig University Hospital
city: Cairo
country: Egypt
facility: Abu El Rich Hospital, Cairo University Hospital
city: Cairo
country: Egypt
facility: Ain Shams University Hospital-Clinical Research Center (MASRI)
city: Accra
country: Ghana
facility: Department of Child Health, University of Ghana Medical School, College of Health Sciences
city: Kumasi
country: Ghana
facility: Komfo Anokye Teaching Hospital
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria (AOU) Meyer
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria (A.O.U.) "Luigi Vanvitelli"
city: Padova
country: Italy
facility: Azienda Ospedaliera Universita (AOU) Padova
city: Kisumu
country: Kenya
facility: Kemri/Crdr,Siaya,Kemri Clinical Research Annex
state: Siaya
city: Nairobi
country: Kenya
facility: KEMRI CRDR Clinical Research Annex
city: Nairobi
country: Kenya
facility: Strathmore University Medical Centre
city: Nairobi
country: Kenya
facility: Gertrude's Children Hospital
city: Enugu
country: Nigeria
facility: University of Nigeria Teaching Hospital
city: Ibadan
country: Nigeria
facility: College of Medicine, University of Ibadan
city: Kaduna
country: Nigeria
facility: Barau Dikko Teaching/ Kaduna State University
city: Kano
country: Nigeria
facility: Aminu Kano Teaching Hospital
city: Lagos
country: Nigeria
facility: Lagos University Teaching Hospital
city: Muscat
country: Oman
facility: Sultan Qaboos University Hospital
city: Riyadh
country: Saudi Arabia
facility: King Abdullah International Medical Research Center (KAIMR) Ministry of National Guard - Health
city: London
country: United Kingdom
facility: Barts Health NHS Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: