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

Primary Purpose

Sickle Cell Disease

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Voxelotor
Placebo
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease focused on measuring Sickle Cell Disease, Transcranial Doppler Ultrasound (TCD)

Eligibility Criteria

2 Years - 14 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male or female participants with Sickle Cell Anemia (SCA)
  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 (see Section 7.2.5.1 for the definition of VOC).
  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 (eg, moyamoya or significant 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

Sites / Locations

  • Children's of Alabama
  • Children's National Medical Center
  • University of Miami
  • Children's Healthcare of Atlanta: Hughes Spalding
  • Children's Healthcare of Atlanta AFLAC Center
  • Children's Healthcare of Atlanta: Scottish Rite
  • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Boston Childien's Hospital - Clinical Research Pharmacy
  • Boston Children's Hospital - Clinical Research Pharmacy
  • Boston Children's Hospital
  • Children's Hospital of Michigan
  • University of Mississippi Medical Center
  • Washington University School of Medicine
  • The Children's Hospital of Philadelphia
  • UPMC Children's Hospital of Pittsburgh
  • Medical University of South Carolina: Investigational Drug Services
  • Medical University of South Carolina: Shawn Jenkins Women's and Children's Hospital
  • Medical University of South Carolina
  • St. Jude Children's Research Hospital - Pharmaceutical Services
  • St. Jude Children's Research Hospital
  • Texas Children's Hospital - Investigational Pharmacy
  • Texas Children's Hospital- Wallace Tower
  • Texas Children's Hospital
  • Ain Shams University Hospital- Clinical Research Center (MASRI)
  • Zagazig University Hospital
  • Alexandria Clinical Research Center, Faculty of Medicine, Alexandria University
  • Abu El Rich Hospital, Cairo University Hospital
  • Abu Elrish Children Hospital
  • Egyptian Thalassemia Association (satellite site)
  • AP-HP Hopital Robert Debré
  • Komfo Anokye Teaching Hospital
  • Department of Child Health, University of Ghana Medical School, College of Health Sciences, Korle-Bu
  • Azienda Ospedaliera Universitaria Meyer "A.O.U. Meyer" - SOC "Oncologia, Ematologia e TCSE"
  • Azienda Ospedaliera Universitaria (A.O.U.) "Luigi Vanvitelli"
  • Azienda Ospedaliera Universita' (AOU ) Padova
  • Azienda Ospedaliera Universita' (AOU) Padova
  • Kemri/Crdr,Siaya,Kemri Clinical Research Annex
  • KEMRI CRDR Clinical Research Annex
  • Strathmore University Medical Centre
  • Gertrude's Children Hospital
  • Lagos University Teaching Hospital
  • College of Medicine, University of Ibadan
  • University of Nigeria Teaching Hospital
  • Barau Dikko Teaching/Kaduna State University
  • Aminu Kano Teaching Hospital
  • Sultan Qaboos University Hospital
  • Sultan َQaboos University Hospital
  • King Saud University Medical City
  • King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard - Health
  • Barts Health NHS Trust
  • King's College Hospital NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Voxelotor

Placebo

Arm Description

Voxelotor 1500mg or equivalent daily as a tablet, dispersible tablet, or as powder for oral suspension.

Matching placebo.

Outcomes

Primary Outcome Measures

TCD Measurement
The change in time averaged maximum of the mean velocity (TAMMV) arterial cerebral blood flow, as measured by TCD.

Secondary Outcome Measures

Change in TCD Flow Velocity
Time to Conversion to Abnormal TCD Flow Velocity
Time to conversion to abnormal TCD flow velocity (≥ 200 cm/sec)
Time to Reversion to Normal TCD Flow Velocity
Time to reversion to normal TCD flow velocity (<170 cm/sec)
TCD Flow Velocity Reduction
Proportion of participants with TCD flow velocity reduction ≥ 15 cm/sec
Number of Participants with Change in Hemoglobin (Hb) from baseline
Change in Unconjugated Bilirubin from baseline
Change in Percent of Reticulocyte from baseline
Change in Absolute Reticulocyte from baseline
Change in Lactate Dehydrogenase (LDH) from baseline

Full Information

First Posted
December 20, 2019
Last Updated
October 4, 2023
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT04218084
Brief Title
Study to Evaluate the Effect of GBT440 on TCD in Pediatrics With Sickle Cell Disease
Acronym
HOPE Kids 2
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 11, 2020 (Actual)
Primary Completion Date
August 24, 2023 (Actual)
Study Completion Date
January 28, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
Keywords
Sickle Cell Disease, Transcranial Doppler Ultrasound (TCD)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-Blind, Placebo-Controlled
Allocation
Randomized
Enrollment
236 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Voxelotor
Arm Type
Experimental
Arm Description
Voxelotor 1500mg or equivalent daily as a tablet, dispersible tablet, or as powder for oral suspension.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo.
Intervention Type
Drug
Intervention Name(s)
Voxelotor
Intervention Description
Participants are randomized 1:1 to receive voxelotor or placebo.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo.
Primary Outcome Measure Information:
Title
TCD Measurement
Description
The change in time averaged maximum of the mean velocity (TAMMV) arterial cerebral blood flow, as measured by TCD.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Change in TCD Flow Velocity
Time Frame
48 and 96 weeks
Title
Time to Conversion to Abnormal TCD Flow Velocity
Description
Time to conversion to abnormal TCD flow velocity (≥ 200 cm/sec)
Time Frame
24, 48, and 96 weeks
Title
Time to Reversion to Normal TCD Flow Velocity
Description
Time to reversion to normal TCD flow velocity (<170 cm/sec)
Time Frame
24, 48, and 96 weeks
Title
TCD Flow Velocity Reduction
Description
Proportion of participants with TCD flow velocity reduction ≥ 15 cm/sec
Time Frame
24, 48, and 96 weeks
Title
Number of Participants with Change in Hemoglobin (Hb) from baseline
Time Frame
baseline, 24, 48, and 96 weeks
Title
Change in Unconjugated Bilirubin from baseline
Time Frame
baseline, 24, 48 and 96 weeks
Title
Change in Percent of Reticulocyte from baseline
Time Frame
baseline, 24, 48, and 96 weeks
Title
Change in Absolute Reticulocyte from baseline
Time Frame
baseline, 24, 48, and 96 weeks
Title
Change in Lactate Dehydrogenase (LDH) from baseline
Time Frame
baseline, 24, 48, and 96 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Children's of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Children's Healthcare of Atlanta: Hughes Spalding
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Children's Healthcare of Atlanta AFLAC Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Children's Healthcare of Atlanta: Scottish Rite
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Boston Childien's Hospital - Clinical Research Pharmacy
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Boston Children's Hospital - Clinical Research Pharmacy
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Children's Hospital of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
UPMC Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Medical University of South Carolina: Investigational Drug Services
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Medical University of South Carolina: Shawn Jenkins Women's and Children's Hospital
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
St. Jude Children's Research Hospital - Pharmaceutical Services
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Texas Children's Hospital - Investigational Pharmacy
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Texas Children's Hospital- Wallace Tower
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Ain Shams University Hospital- Clinical Research Center (MASRI)
City
Cairo
State/Province
Abassia
ZIP/Postal Code
11566
Country
Egypt
Facility Name
Zagazig University Hospital
City
Zagazig
State/Province
Alsharkia
Country
Egypt
Facility Name
Alexandria Clinical Research Center, Faculty of Medicine, Alexandria University
City
Alexandria
ZIP/Postal Code
21131
Country
Egypt
Facility Name
Abu El Rich Hospital, Cairo University Hospital
City
Cairo
Country
Egypt
Facility Name
Abu Elrish Children Hospital
City
Cairo
Country
Egypt
Facility Name
Egyptian Thalassemia Association (satellite site)
City
Cairo
Country
Egypt
Facility Name
AP-HP Hopital Robert Debré
City
Paris
ZIP/Postal Code
75019
Country
France
Facility Name
Komfo Anokye Teaching Hospital
City
Kumasi
State/Province
Ashanti
ZIP/Postal Code
00233
Country
Ghana
Facility Name
Department of Child Health, University of Ghana Medical School, College of Health Sciences, Korle-Bu
City
Accra
State/Province
Greater Accra
ZIP/Postal Code
GA-221-1570
Country
Ghana
Facility Name
Azienda Ospedaliera Universitaria Meyer "A.O.U. Meyer" - SOC "Oncologia, Ematologia e TCSE"
City
Firenze
ZIP/Postal Code
50139
Country
Italy
Facility Name
Azienda Ospedaliera Universitaria (A.O.U.) "Luigi Vanvitelli"
City
Napoli
ZIP/Postal Code
80138
Country
Italy
Facility Name
Azienda Ospedaliera Universita' (AOU ) Padova
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Azienda Ospedaliera Universita' (AOU) Padova
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Kemri/Crdr,Siaya,Kemri Clinical Research Annex
City
Kisumu
State/Province
Siaya
ZIP/Postal Code
40600
Country
Kenya
Facility Name
KEMRI CRDR Clinical Research Annex
City
Nairobi
ZIP/Postal Code
00100
Country
Kenya
Facility Name
Strathmore University Medical Centre
City
Nairobi
ZIP/Postal Code
00200
Country
Kenya
Facility Name
Gertrude's Children Hospital
City
Nairobi
ZIP/Postal Code
100
Country
Kenya
Facility Name
Lagos University Teaching Hospital
City
Surulere
State/Province
Lagos
ZIP/Postal Code
100254
Country
Nigeria
Facility Name
College of Medicine, University of Ibadan
City
Ibadan
State/Province
OYO State
ZIP/Postal Code
200212
Country
Nigeria
Facility Name
University of Nigeria Teaching Hospital
City
Enugu
ZIP/Postal Code
460000
Country
Nigeria
Facility Name
Barau Dikko Teaching/Kaduna State University
City
Kaduna
ZIP/Postal Code
800242
Country
Nigeria
Facility Name
Aminu Kano Teaching Hospital
City
Kano
ZIP/Postal Code
70001
Country
Nigeria
Facility Name
Sultan Qaboos University Hospital
City
Muscat
ZIP/Postal Code
123
Country
Oman
Facility Name
Sultan َQaboos University Hospital
City
Muscat
Country
Oman
Facility Name
King Saud University Medical City
City
Riyadh
ZIP/Postal Code
11472
Country
Saudi Arabia
Facility Name
King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard - Health
City
Riyadh
ZIP/Postal Code
11481
Country
Saudi Arabia
Facility Name
Barts Health NHS Trust
City
London
ZIP/Postal Code
E1 1BB
Country
United Kingdom
Facility Name
King's College Hospital NHS Foundation Trust
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=GBT440-032
Description
To obtain contact information for a study center near you, click here.

Learn more about this trial

Study to Evaluate the Effect of GBT440 on TCD in Pediatrics With Sickle Cell Disease

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