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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Voxelotor

• Study Type: Interventional
• Enrollment (Estimated): 148
• Phase: Phase 2

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Pfizer CT.gov Call Center; Phone Number: 1-800-718-1021; Email: ClinicalTrials.gov_Inquiries@pfizer.com

Study Locations

• Lebanon
  • Beirut, Lebanon
    • Rafik Hariri University Hospital
  • Beirut, Lebanon
    • American University of Beirut - Medical Center
  • Tripoli, Lebanon
    • Nini Hospital
• United Kingdom
  • London, United Kingdom, E1 1BB
    • Barts Health NHS Trust, The Royal London Hospital
  • London, United Kingdom, SE1 7EH
    • Guy's and St Thoma's NHS Foundation Trust, Evelina London Children's Hospital
  • Manchester, United Kingdom, M13 9WL
    • Manchester University NHS Foundation Trust, Royal Manchester Children's Hospital
  • Greater London
    • London, Greater London, United Kingdom, NW1 2PG
      • University College London Hospital, NHS Foundation Trust
• United States
  • California
    • Brentwood, California, United States, 94513
      • Brentwood Clinic UCSF Benioff Children's Hospital Oakland
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital Oakland
    • Walnut Creek, California, United States, 94598
      • UCSF Benioff Children's Hospital Walnut Creek
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Children's 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
    • Chicago, Illinois, United States, 60612
      • University of Illinois Hospital and Health Sciences System
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago Clinical Research Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Our Lady of the Lake Children's Hospital (IP Address)
    • Baton Rouge, Louisiana, United States, 70809
      • St. Jude Affiliate Clinic at Our Lady of the Lake Children's Health
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Robert Wood Johnson University Hospital
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers-Robert Wood Johnson Medical School
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers-Robert Wood Johnson Medical School
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Brody School of Medicine at East Carolina University
    • Greenville, North Carolina, United States, 27834
      • ECU Physicians
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center, Rainbow Babies & Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • 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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Voxelotor; 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)

Drug: Voxelotor; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Pre-dose to Day 15
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	Pre-dose to Day 15
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	Pre-dose to Day 15
Part B: Change in hemoglobin	Change from baseline to Week 24 in Hb	Baseline to Week 24
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	Baseline to Week 48
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.	Baseline to Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03		Days 1 - 15
Part B: Multiple Dose effect on Clinical Measures of Hemolysis		Day 1 - Week 24
Part B: Pharmacokinetic profile of voxelotor including maximum concentration		Pre-dose to Week 24
Part B: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration		Pre-dose to Week 24
Part B: Pharmacokinetic profile of voxelotor including the total drug concentration over time		Pre-dose to Week 24
Part C: Multiple dose effect on clinical measures of hemolysis		Baseline to Week 24 and Week 48
Part C: Change in cerebral blood flow as measured by TAMM TCD velocity		Baseline to Week 24
Part C: Time to initial Hemoglobin response	Change from baseline in Hb > 1g/dL	Baseline to Week 48
Part C: Pharmacokinetic profile of voxelotor including percent Hemoglobin occupancy		Baseline to Week 48
Part C: Proportion of participants with normal TCD flow velocity		Baseline to Week 48
Part C: Incidence of stroke and VOC		Baseline to Week 48
Part D: Pharmacokinetic profile of voxelotor including percent Hemoglobin occupancy		Baseline to Week 48
Part D: Change in Hemoglobin		Baseline to Week 24 and Week 48
Part D: Change in Lactate Dehydrogenase		Baseline to Week 24 and Week 48
Part D: Change in Indirect Bilirubin		Baseline to Week 24 and Week 48
Part D: Change in Reticulocyte Count		Baseline to Week 24 and Week 48
Part D: Time to initial Hemoglobin response	Change from baseline in Hb > 1g/dL	Baseline to Week 48
Part D: Incidence of stroke and VOC		Baseline to Week 48

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2016
• Primary Completion (Estimated): January 4, 2025
• Study Completion (Estimated): January 4, 2025

Study Registration Dates

• First Submitted: July 1, 2016
• First Submitted That Met QC Criteria: July 27, 2016
• First Posted (Estimated): August 1, 2016

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 26, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: GBT440-007; C5341020 (Other Identifier: Alias Study 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