Study to Evaluate the Effect of GBT440 on TCD in Pediatrics With Sickle Cell Disease (HOPE Kids 2)

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Voxelotor (GBT440) in Pediatric Participants With Sickle Cell Disease (HOPE Kids 2)

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.

Study Overview

• Status: Terminated
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Placebo; Drug: Voxelotor

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.

• Study Type: Interventional
• Enrollment (Actual): 236
• Phase: Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt, 21131
    • Alexandria Clinical Research Center, Faculty of Medicine, Alexandria University
  • Cairo, Egypt, 11562
    • Abu El Rich Hospital, Cairo University Hospital
  • Abassia
    • Cairo, Abassia, Egypt, 11566
      • Ain Shams University Hospital- Clinical Research Center (MASRI)
  • Alsharkia
    • Zagazig, Alsharkia, Egypt
      • Zagazig university hospital
• Ghana
  • Ashanti Region
    • Kumasi, Ashanti Region, Ghana, 00233
      • Komfo Anokye Teaching Hospital
  • Greater Accra Region
    • Accra, Greater Accra Region, Ghana, GA-221-1570
      • Department of Child Health, University of Ghana Medical School, College of Health Sciences, Korle-Bu
• Italy
  • Florence, Italy, 50139
    • Azienda Ospedaliera Universitaria Meyer "A.O.U. Meyer" - SOC "Oncologia, Ematologia e TCSE"
  • Napoli, Italy, 80138
    • Azienda Ospedaliera Universitaria (A.O.U.) "Luigi Vanvitelli"
  • Padua, Italy, 35128
    • Azienda Ospedaliera Universita' (AOU ) Padova
  • Padua, Italy, 35128
    • Azienda Ospedaliera Universita' (AOU) Padova
• Kenya
  • Nairobi, Kenya, 00100
    • KEMRI CRDR Clinical Research Annex
  • Nairobi, Kenya, 00200
    • Strathmore University Medical Centre
  • Nairobi, Kenya, 100
    • Gertrude's Children Hospital
  • Siaya County
    • Kisumu, Siaya County, Kenya, 40600
      • Kemri/Crdr,Siaya,Kemri Clinical Research Annex
• Nigeria
  • Enugu, Nigeria, 460000
    • University of Nigeria Teaching Hospital
  • Kaduna, Nigeria, 800212
    • Barau Dikko Teaching/Kaduna State University
  • Kano, Nigeria, 700233
    • Aminu Kano Teaching Hospital
  • Lagos
    • Surulere, Lagos, Nigeria, 100254
      • Lagos University Teaching Hospital
  • Oyo State
    • Ibadan, Oyo State, Nigeria, 200212
      • College of Medicine, University of Ibadan
• Oman
  • Muscat, Oman
    • Sultan Qaboos University Hospital
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11481
    • King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard - Health
• United Kingdom
  • London, United Kingdom, E1 1BB
    • Barts Health NHS Trust
• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Children's Healthcare of Atlanta: Hughes Spalding
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital - Clinical Research Pharmacy
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina: Investigational Drug Services
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina: Shawn Jenkins Women's and Children's Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital - Investigational Pharmacy
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital- Wallace Tower

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 14 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo.	Drug: Placebo; Matching placebo.
Experimental: Voxelotor; Voxelotor 1500mg or equivalent daily as a tablet, dispersible tablet, or as powder for oral suspension.	Drug: Voxelotor; Participants are randomized 1:1 to receive voxelotor or placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Time-Averaged Maximum of Mean Velocity (TAMMV) Arterial Cerebral Blood Flow at Week 24	TAMMV is an ultrasound measurement used in transcranial Doppler (TCD) to assess blood flow in cerebral arteries. TCD flow velocities were categorized as follows: (i) Normal: < 170 centimeter per second (cm/sec); (ii) Conditional: 170 to < 200 cm/sec - the eligible participant population for this study; (iii) Abnormal: >= 200 cm/sec.	Baseline (value at screening), Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in TAMMV Arterial Cerebral Blood Flow at Week 48	TAMMV is an ultrasound measurement used in TCD to assess blood flow in cerebral arteries. TCD flow velocities were categorized as follows: (i) Normal: < 170 cm/sec; (ii) Conditional: 170 to < 200 cm/sec - the eligible participant population for this study; (iii) Abnormal: >= 200 cm/sec.	Baseline (value at Screening), Weeks 48
Time to Conversion to Abnormal TCD Flow	Time to conversion was the number of weeks from the date of randomization to the date of first determined TCD assessment when an abnormal TCD flow velocity (>= 200 cm/sec) was determined. TCD flow velocities were categorized as follows: (i) Normal: < 170 cm/sec; (ii) Conditional: 170 to < 200 cm/sec - the eligible participant population for this study; (iii) Abnormal: >= 200 cm/sec. The stratified Log Rank Test was stratified by stratification factors: baseline HU use (yes; no), age group (2 to <= 8 years; >8 to <15 years), and baseline TAMMV value (170 cm/sec to < 185 cm/sec; 185 cm/sec to < 200 cm/sec).	Up to 96 weeks
Time to Reversion to Normal TCD Flow	TCD was used to assess cerebral artery blood flow velocity in children with sickle cell disease (SCD). Time to first normal TCD flow was the number of weeks from randomization to the date of first determined normal TCD flow. Normal is < 170 cm/sec.	Up to 96 weeks
Percentage of Participants With TAMMV Reduced by >=15 cm/Sec From Baseline at Weeks 24, 48 and 96	In this outcome measure, percentage of participants whose TAMMV reduced by >=15 cm/sec from Baseline at Weeks 24, 48 and 96 is reported. TAMMV is an ultrasound measurement used in TCD to assess blood flow in cerebral arteries. TCD flow velocities are categorized as follows: (i) Normal: < 170 cm/sec; (ii) Conditional: 170 to < 200 cm/sec - the eligible participant population for this study; (iii) Abnormal: >= 200 cm/sec.	At Weeks 24, 48 and 96
Change From Baseline in Hemoglobin (Hb) at Weeks 24, 48 and 96	Change from baseline in hemoglobin at weeks 24, 48 and 96 were reported in this outcome measure.	Baseline (value at Screening), Weeks 24, 48 and 96
Percent Change From Baseline in Unconjugated Bilirubin at Weeks 24, 48 and 96	Percent change from baseline in unconjugated bilirubin at weeks 24, 48 and 96 was reported in this outcome measure.	Baseline (value at Screening), Weeks 24, 48 and 96
Percent Change From Baseline in Reticulocyte at Weeks 24, 48 and 96	Percent change from baseline in reticulocyte at weeks 24, 48 and 96 was reported in this outcome measure.	Baseline (value at Screening), Weeks 24, 48 and 96
Percent Change From Baseline in Absolute Reticulocyte at Weeks 24, 48 and 96	Percent change from baseline in absolute reticulocyte at weeks 24, 48 and 96 was reported in this outcome measure.	Baseline (value at Screening), Weeks 24, 48 and 96
Percent Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 24, 48 and 96	Percent change from baseline in LDH at weeks 24, 48 and 96 was reported in this outcome measure.	Baseline (value at Screening), Weeks 24, 48 and 96
Annualized Incidence Rate of Vaso-Occlusive Crises (VOCs)	VOC was defined as a composite of acute painful crisis and/or acute chest syndrome (ACS). Annualized incidence rate was defined as total number of events per total person-years on treatment. Total person-years was the sum of participants treatment period in years, which included the time from randomization date to the earliest of (last dose date, post-randomization HU initiation for participants with no HU at baseline, end of study, or study termination). The 95% CI of rate displayed the exact Poisson confidence limits.	From randomization to the last dose date, post-randomization HU initiation with no HU at baseline, end of study or study termination, whichever occurred earlier (maximum up to 110 weeks)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2020
• Primary Completion (Actual): January 18, 2024
• Study Completion (Actual): November 6, 2024

Study Registration Dates

• First Submitted: December 20, 2019
• First Submitted That Met QC Criteria: January 2, 2020
• First Posted (Actual): January 6, 2020

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Sickle Cell Disease; Transcranial Doppler Ultrasound (TCD)
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; voxelotor
• Other Study ID Numbers: GBT440-032; C5341021 (Other Identifier: Alias Study Number); 2017-000903-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No