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

Primary Purpose

Sickle Cell Disease

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Voxelotor
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sickle Cell Disease

Eligibility Criteria

6 Months - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female participants with homozygous hemoglobin SS (HbSS) or hemoglobin S beta0 thalassemia (HbS β0thal)

  • Age:

    • Part A - 6 to 17 years of age
    • Part B - 12 to 17 years of age
    • Part C - 4 to 17 years of age
    • Part D - 6 months to <4 years of age

  • Hydroxyurea (HU) therapy:

    • Parts A, B, and C: A participant taking hydroxyurea (HU) may be enrolled if the dose has been stable for at least 3 months with no anticipated need for dose adjustment during the study and no sign of hematological toxicity.
    • Part D: A participant taking HU may be enrolled if the dose has been stable for at least 1 month. Titration to the maximum tolerated dose (MTD) is allowed during the study.

  • Hemoglobin (HB):

    • Part A - No restriction
    • Parts B, C, & D - Hb ≤ 10.5 g/dL
  • For Part C only: Participants 12 to 17 years of age must have a TCD velocity of ≥ 140 cm/sec measured anytime during screening.

Exclusion Criteria:

  • Any one of the following requiring medical attention within 14 days of signing the Informed Consent Form (ICF):

    • Vaso-occlusive crisis (VOC)
    • Acute chest syndrome (ACS)
    • Splenic sequestration crisis
    • Dactylitis
  • Requires chronic transfusion therapy
  • History of stroke or meeting criteria for primary stroke prophylaxis (history of two TCD measurements ≥ 200 cm/sec by non-imaging TCD or ≥185 cm/sec by TCDi).
  • Transfusion within 30 days prior to signing the ICF

Exclusion Criteria for Part D Only:

  • Body weight <5 kg for 1 month prior to the screening visit and at the screening visit.

Sites / Locations

  • Brentwood Clinic UCSF Benioff Children's Hospital Oakland
  • UCSF Benioff Children's Hospital Oakland
  • UCSF Benioff Children's Hospital Walnut Creek
  • Children's National Medical Center
  • Emory Children's Center
  • Children's Healthcare of Atlanta Scottish Rite
  • Ann & Robert H. Lurie Children's Hospital of Chicago
  • University of Illinois at Chicago Clinical Research Center
  • University of Illinois Hospital and Health Sciences System
  • Our Lady of the Lake Children's Hospital (IP Address)
  • St. Jude Affiliate Clinic at Our Lady of the Lake Children's Health
  • Children's Mercy Hospital
  • Robert Wood Johnson University Hospital
  • Rutgers-Robert Wood Johnson Medical School
  • Rutgers-Robert Wood Johnson Medical School
  • Brody School of Medicine at East Carolina UniversityRecruiting
  • ECU PhysiciansRecruiting
  • University Hospitals Cleveland Medical Center, Rainbow Babies & Children's Hospital
  • The Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh of UPMC
  • St. Jude Children's Research Hospital - Pharmaceutical ServicesRecruiting
  • St. Jude Children's Research HospitalRecruiting
  • American University of Beirut - Medical CenterRecruiting
  • Rafik Hariri University Hospital
  • Nini HospitalRecruiting
  • University College London Hospital, NHS Foundation TrustRecruiting
  • Barts Health NHS Trust, The Royal London HospitalRecruiting
  • Guy's and St Thoma's NHS Foundation Trust, Evelina London Children's HospitalRecruiting
  • Manchester University NHS Foundation Trust, Royal Manchester Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Voxelotor

Arm Description

Subjects to receive daily oral dosing of voxelotor according to which Part (A, B, C, or D), the subject is participating in: Part A: Subjects to receive daily oral dosing of voxelotor for 1 day (single dose) Part B: Subjects to receive daily oral dosing of voxelotor for up to 24 weeks (multiple dose) Part C: Subjects to receive daily oral dosing of voxelotor for up to 48 weeks (1500mg or 1500mg equivalent dose) Part D: Subjects to receive daily oral dosing of voxelotor for up to 48 weeks (1500mg equivalent dose)

Outcomes

Primary Outcome Measures

Part A: Pharmacokinetic profile of voxelotor including maximum concentration
Maximum observed concentration (Cmax), area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last), and area under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of voxelotor in whole blood
Part A: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration
Maximum observed concentration (Cmax), area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last), and area under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of voxelotor in whole blood
Part A: Pharmacokinetic profile of voxelotor including the total drug concentration over time
Maximum observed concentration (Cmax), area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last), and area under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of voxelotor in whole blood
Part B: Change in hemoglobin
Change from baseline to Week 24 in Hb
Part C: Change in cerebral blood flow as measured by the TAMM TCD velocity
Change from baseline to 12 and 24 weeks in cerebral blood flow as measured by the time-averaged mean of the maximum (TAMM) TCD velocity
Part D: Treatment-Emergent Adverse Events and Serious Adverse Events
Participants will be monitored throughout the study for AEs, from the time informed consent is obtained through the EOS visit. The Investigator will assess each AE for seriousness, intensity and relationship to investigational product.

Secondary Outcome Measures

Part A: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Part B: Multiple Dose effect on Clinical Measures of Hemolysis
Part B: Pharmacokinetic profile of voxelotor including maximum concentration
Part B: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration
Part B: Pharmacokinetic profile of voxelotor including the total drug concentration over time
Part C: Multiple dose effect on clinical measures of hemolysis
Part C: Change in cerebral blood flow as measured by TAMM TCD velocity
Part C: Time to initial Hemoglobin response
Change from baseline in Hb > 1g/dL
Part C: Pharmacokinetic profile of voxelotor including percent Hemoglobin occupancy
Part C: Proportion of participants with normal TCD flow velocity
Part C: Incidence of stroke and VOC
Part D: Pharmacokinetic profile of voxelotor including percent Hemoglobin occupancy
Part D: Change in Hemoglobin
Part D: Change in Lactate Dehydrogenase
Part D: Change in Indirect Bilirubin
Part D: Change in Reticulocyte Count
Part D: Time to initial Hemoglobin response
Change from baseline in Hb > 1g/dL
Part D: Incidence of stroke and VOC

Full Information

First Posted
July 1, 2016
Last Updated
October 4, 2023
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT02850406
Brief Title
Study to Evaluate the Effect of GBT440 in Pediatrics With Sickle Cell Disease
Acronym
HOPE
Official Title
A Phase 2a, Open-label, Single and Multiple Dose Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Treatment Effect of GBT440 in Pediatric Participants With Sickle Cell Disease
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 5, 2016 (Actual)
Primary Completion Date
January 4, 2025 (Anticipated)
Study Completion Date
January 4, 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 consists of four parts, Parts A, B, C, and D. Part A is a single dose pharmacokinetic (PK) study in pediatric participants with Sickle Cell Disease ages 6 to 17 years. Part B is a multiple dose, safety, exploratory, efficacy, and PK study in adolescent participants with Sickle Cell Disease ages 12 to 17 years. Part C is a multiple dose, safety, tolerability, and PK study, which includes the assessment of hematological effects and the effect on TCD flow velocity of voxelotor in pediatric participants with Sickle Cell Disease ages 4 to 17 years. Part D is a multiple dose, safety, tolerability, and PK study, which examines the hematological effects of voxelotor in pediatric participants with Sickle Cell Disease ages 6 months to < 4 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
148 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Voxelotor
Arm Type
Experimental
Arm Description
Subjects to receive daily oral dosing of voxelotor according to which Part (A, B, C, or D), the subject is participating in: Part A: Subjects to receive daily oral dosing of voxelotor for 1 day (single dose) Part B: Subjects to receive daily oral dosing of voxelotor for up to 24 weeks (multiple dose) Part C: Subjects to receive daily oral dosing of voxelotor for up to 48 weeks (1500mg or 1500mg equivalent dose) Part D: Subjects to receive daily oral dosing of voxelotor for up to 48 weeks (1500mg equivalent dose)
Intervention Type
Drug
Intervention Name(s)
Voxelotor
Intervention Description
Part A: Voxelotor will be administered as oral capsules or tablets Part B: Voxelotor will be administered as oral capsules or tablets Part C: Voxelotor will be administered as oral dispersible tablets or powder for oral suspension Part D: Voxelotor will be administered as oral dispersible tablets or powder for oral suspension
Primary Outcome Measure Information:
Title
Part A: Pharmacokinetic profile of voxelotor including maximum concentration
Description
Maximum observed concentration (Cmax), area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last), and area under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of voxelotor in whole blood
Time Frame
Pre-dose to Day 15
Title
Part A: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration
Description
Maximum observed concentration (Cmax), area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last), and area under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of voxelotor in whole blood
Time Frame
Pre-dose to Day 15
Title
Part A: Pharmacokinetic profile of voxelotor including the total drug concentration over time
Description
Maximum observed concentration (Cmax), area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last), and area under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of voxelotor in whole blood
Time Frame
Pre-dose to Day 15
Title
Part B: Change in hemoglobin
Description
Change from baseline to Week 24 in Hb
Time Frame
Baseline to Week 24
Title
Part C: Change in cerebral blood flow as measured by the TAMM TCD velocity
Description
Change from baseline to 12 and 24 weeks in cerebral blood flow as measured by the time-averaged mean of the maximum (TAMM) TCD velocity
Time Frame
Baseline to Week 48
Title
Part D: Treatment-Emergent Adverse Events and Serious Adverse Events
Description
Participants will be monitored throughout the study for AEs, from the time informed consent is obtained through the EOS visit. The Investigator will assess each AE for seriousness, intensity and relationship to investigational product.
Time Frame
Baseline to Week 48
Secondary Outcome Measure Information:
Title
Part A: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Time Frame
Days 1 - 15
Title
Part B: Multiple Dose effect on Clinical Measures of Hemolysis
Time Frame
Day 1 - Week 24
Title
Part B: Pharmacokinetic profile of voxelotor including maximum concentration
Time Frame
Pre-dose to Week 24
Title
Part B: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration
Time Frame
Pre-dose to Week 24
Title
Part B: Pharmacokinetic profile of voxelotor including the total drug concentration over time
Time Frame
Pre-dose to Week 24
Title
Part C: Multiple dose effect on clinical measures of hemolysis
Time Frame
Baseline to Week 24 and Week 48
Title
Part C: Change in cerebral blood flow as measured by TAMM TCD velocity
Time Frame
Baseline to Week 24
Title
Part C: Time to initial Hemoglobin response
Description
Change from baseline in Hb > 1g/dL
Time Frame
Baseline to Week 48
Title
Part C: Pharmacokinetic profile of voxelotor including percent Hemoglobin occupancy
Time Frame
Baseline to Week 48
Title
Part C: Proportion of participants with normal TCD flow velocity
Time Frame
Baseline to Week 48
Title
Part C: Incidence of stroke and VOC
Time Frame
Baseline to Week 48
Title
Part D: Pharmacokinetic profile of voxelotor including percent Hemoglobin occupancy
Time Frame
Baseline to Week 48
Title
Part D: Change in Hemoglobin
Time Frame
Baseline to Week 24 and Week 48
Title
Part D: Change in Lactate Dehydrogenase
Time Frame
Baseline to Week 24 and Week 48
Title
Part D: Change in Indirect Bilirubin
Time Frame
Baseline to Week 24 and Week 48
Title
Part D: Change in Reticulocyte Count
Time Frame
Baseline to Week 24 and Week 48
Title
Part D: Time to initial Hemoglobin response
Description
Change from baseline in Hb > 1g/dL
Time Frame
Baseline to Week 48
Title
Part D: Incidence of stroke and VOC
Time Frame
Baseline to Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female participants with homozygous hemoglobin SS (HbSS) or hemoglobin S beta0 thalassemia (HbS β0thal) Age: Part A - 6 to 17 years of age Part B - 12 to 17 years of age Part C - 4 to 17 years of age Part D - 6 months to <4 years of age Hydroxyurea (HU) therapy: Parts A, B, and C: A participant taking hydroxyurea (HU) may be enrolled if the dose has been stable for at least 3 months with no anticipated need for dose adjustment during the study and no sign of hematological toxicity. Part D: A participant taking HU may be enrolled if the dose has been stable for at least 1 month. Titration to the maximum tolerated dose (MTD) is allowed during the study. Hemoglobin (HB): Part A - No restriction Parts B, C, & D - Hb ≤ 10.5 g/dL For Part C only: Participants 12 to 17 years of age must have a TCD velocity of ≥ 140 cm/sec measured anytime during screening. Exclusion Criteria: Any one of the following requiring medical attention within 14 days of signing the Informed Consent Form (ICF): Vaso-occlusive crisis (VOC) Acute chest syndrome (ACS) Splenic sequestration crisis Dactylitis Requires chronic transfusion therapy History of stroke or meeting criteria for primary stroke prophylaxis (history of two TCD measurements ≥ 200 cm/sec by non-imaging TCD or ≥185 cm/sec by TCDi). Transfusion within 30 days prior to signing the ICF Exclusion Criteria for Part D Only: Body weight <5 kg for 1 month prior to the screening visit and at the screening visit.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pfizer CT.gov Call Center
Phone
1-800-718-1021
Email
ClinicalTrials.gov_Inquiries@pfizer.com
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
Brentwood Clinic UCSF Benioff Children's Hospital Oakland
City
Brentwood
State/Province
California
ZIP/Postal Code
94513
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
UCSF Benioff Children's Hospital Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
UCSF Benioff Children's Hospital Walnut Creek
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Emory Children's Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Children's Healthcare of Atlanta Scottish Rite
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Ann & Robert H. Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
University of Illinois at Chicago Clinical Research Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
University of Illinois Hospital and Health Sciences System
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Our Lady of the Lake Children's Hospital (IP Address)
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70809
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
St. Jude Affiliate Clinic at Our Lady of the Lake Children's Health
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70809
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Robert Wood Johnson University Hospital
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Rutgers-Robert Wood Johnson Medical School
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Rutgers-Robert Wood Johnson Medical School
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08903
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Brody School of Medicine at East Carolina University
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Individual Site Status
Recruiting
Facility Name
ECU Physicians
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Individual Site Status
Recruiting
Facility Name
University Hospitals Cleveland Medical Center, Rainbow Babies & Children's Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Children's Hospital of Pittsburgh of UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
St. Jude Children's Research Hospital - Pharmaceutical Services
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Individual Site Status
Recruiting
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Individual Site Status
Recruiting
Facility Name
American University of Beirut - Medical Center
City
Beirut
Country
Lebanon
Individual Site Status
Recruiting
Facility Name
Rafik Hariri University Hospital
City
Beirut
Country
Lebanon
Individual Site Status
Active, not recruiting
Facility Name
Nini Hospital
City
Tripoli
Country
Lebanon
Individual Site Status
Recruiting
Facility Name
University College London Hospital, NHS Foundation Trust
City
London
State/Province
Greater London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Barts Health NHS Trust, The Royal London Hospital
City
London
ZIP/Postal Code
E1 1BB
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Guy's and St Thoma's NHS Foundation Trust, Evelina London Children's Hospital
City
London
ZIP/Postal Code
SE1 7EH
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Manchester University NHS Foundation Trust, Royal Manchester Children's Hospital
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Individual Site Status
Active, not recruiting

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
Citations:
PubMed Identifier
35451176
Citation
Estepp JH, Kalpatthi R, Woods G, Trompeter S, Liem RI, Sims K, Inati A, Inusa BPD, Campbell A, Piccone C, Abboud MR, Smith-Whitley K, Dixon S, Tonda M, Washington C, Griffin NM, Brown C. Safety and efficacy of voxelotor in pediatric patients with sickle cell disease aged 4 to 11 years. Pediatr Blood Cancer. 2022 Aug;69(8):e29716. doi: 10.1002/pbc.29716. Epub 2022 Apr 21.
Results Reference
derived
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=GBT440-007
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 in Pediatrics With Sickle Cell Disease

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