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: Active, not recruiting
• 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

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Mark Davis; Phone Number: 925-336-1055; Email: mdavis1@gbt.com
• Study Contact Backup: Name: Jason Farthing; Phone Number: 619-992-0348; Email: jfarthing@gbt.com

Study Locations

• Egypt
  • Alexandria, Egypt, 21131
    • Alexandria Clinical Research Center, Faculty of Medicine, Alexandria University
  • Cairo, Egypt
    • Abu El Rich Hospital, Cairo University Hospital
  • Cairo, Egypt
    • Abu Elrish Children Hospital
  • Cairo, Egypt
    • Egyptian Thalassemia Association (satellite site)
  • Abassia
    • Cairo, Abassia, Egypt, 11566
      • Ain Shams University Hospital- Clinical Research Center (MASRI)
  • Alsharkia
    • Zagazig, Alsharkia, Egypt
      • Zagazig University Hospital
• France
  • Paris, France, 75019
    • AP-HP Hopital Robert Debré
• Ghana
  • Ashanti
    • Kumasi, Ashanti, Ghana, 00233
      • Komfo Anokye Teaching Hospital
  • Greater Accra
    • Accra, Greater Accra, Ghana, GA-221-1570
      • Department of Child Health, University of Ghana Medical School, College of Health Sciences, Korle-Bu
• Italy
  • Firenze, 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"
  • Padova, Italy, 35128
    • Azienda Ospedaliera Universita' (AOU ) Padova
  • Padova, 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
    • Kisumu, Siaya, Kenya, 40600
      • Kemri/Crdr,Siaya,Kemri Clinical Research Annex
• Nigeria
  • Enugu, Nigeria, 460000
    • University of Nigeria Teaching Hospital
  • Kaduna, Nigeria, 800242
    • Barau Dikko Teaching/Kaduna State University
  • Kano, Nigeria, 70001
    • 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, 123
    • Sultan Qaboos University Hospital
  • Muscat, Oman
    • Sultan Qaboos University Hospital
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11472
    • King Saud University Medical City
  • Riyadh, Saudi Arabia, 11481
    • King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard - Health
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust
  • London, United Kingdom, E1 1BB
    • Barts Health NHS Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's of Alabama
  • District of Columbia
    • Washington, 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
    • Atlanta, Georgia, United States, 30342
      • Children's Healthcare of Atlanta AFLAC Center
    • Atlanta, Georgia, United States, 30342
      • Children's Healthcare of Atlanta: Scottish Rite
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
    • Boston, Massachusetts, United States, 02115
      • Boston Childien's Hospital - Clinical Research Pharmacy
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital - Clinical Research Pharmacy
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
  • 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
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital - Pharmaceutical Services
  • 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
TCD Measurement	The change in time averaged maximum of the mean velocity (TAMMV) arterial cerebral blood flow, as measured by TCD.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in TCD Flow Velocity		48 and 96 weeks
TCD Flow Velocity Reduction	Proportion of participants with TCD flow velocity reduction ≥ 15 cm/sec	24, 48, and 96 weeks
Time to Conversion to Abnormal TCD Flow Velocity	Time to conversion to abnormal TCD flow velocity (≥ 200 cm/sec)	24, 48, and 96 weeks
Time to Reversion to Normal TCD Flow Velocity	Time to reversion to normal TCD flow velocity (<170 cm/sec)	24, 48, and 96 weeks
Number of Participants with Change in Hemoglobin (Hb) from baseline		baseline, 24, 48, and 96 weeks
Change in Unconjugated Bilirubin from baseline		baseline, 24, 48 and 96 weeks
Change in Percent of Reticulocyte 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

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): August 24, 2023
• Study Completion (Estimated): January 28, 2025

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 (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Sickle Cell Disease; Transcranial Doppler Ultrasound (TCD)
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• 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