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

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

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 2

Expanded Access

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

Contacts and Locations

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
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Georgia
    • 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 at Chicago Clinical Research Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Our Lady of the Lake Children's Hospital (IP Address)
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • New Jersey
    • 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
  • 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

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: Maximum Concentration (Cmax) of Voxelotor in Whole Blood		pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Voxelotor in Whole Blood	AUC0-last was calculated using the linear/log trapezoid rule.	pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor in Whole Blood	AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration for whole blood and lambdaz=elimination rate constant.	pre-dose, 2, 8, 24, 48, 96,168 and 336 hours post-dose
Part B: Change From Baseline to Week 24 in Hemoglobin Level		Baseline, Week 24
Part C: Change From Baseline to Week 48 in Cerebral Blood Flow	Cerebral blood flow was measured using transcranial Doppler (TCD) sonography. Change from baseline in cerebral blood flow as measured by the time-averaged mean of the maximum (TAMM) TCD velocity is reported.	Baseline, Week 48
Part D: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. TEAE was defined as an AE that emerged on or after initiation of study drug (having been absent pre-treatment), or an AE that existed pre-treatment and worsened on treatment (relative to the pre-treatment state) through 28 days after study drug discontinuation. An SAE was any AE that resulted in any of the following outcomes: death, life threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, other important medical events. AEs were classified as SCD-related and non-SCD related.	From start of study treatment up to 28 days after study treatment discontinuation (Up to 52 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Maximum Concentration (Cmax) of Voxelotor in Plasma		pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Part A: Maximum Concentration (Cmax) of Voxelotor in Red Blood Cells (RBC)		pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Voxelotor in Plasma	AUC0-last was calculated using the linear/log trapezoid rule.	pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Voxelotor in RBC	AUC0-last was calculated using the linear/log trapezoid rule.	pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor in Plasma	AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration for plasma and lambdaz is the elimination rate constant.	pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Part A: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor in RBC	AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration and lambdaz is the elimination rate constant.	pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Part A: Time at Which Cmax Was Observed (Tmax) for Voxelotor in Whole Blood		pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Part A: Time at Which Cmax Was Observed (Tmax) for Voxelotor in Plasma		pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Part A: Time at Which Cmax Was Observed (Tmax) for Voxelotor in RBC		pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Part A: Terminal Elimination Half-Life (T1/2) for Voxelotor in Whole Blood	T1/2 was the time measured for the drug concentration to decrease by one half.	pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Part A: Terminal Elimination Half-Life (T1/2) for Voxelotor in Plasma	T1/2 was the time measured for the drug concentration to decrease by one half.	pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Part A: Terminal Elimination Half-Life (T1/2) for Voxelotor in RBC	T1/2 was the time measured for the drug concentration to decrease by one half.	pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose
Part A: Percentage Hemoglobin (Hb) Occupancy	Percentage hemoglobin occupancy (% Hb Occupancy) refers to the percentage of hemoglobin molecules within red blood cells that were bound to study drug. Concentration of voxelotor in whole blood and plasma was used to calculate %Hb occupancy. Percentage Hb occupancy within RBCs was estimated using the formula: ([Concentration of voxelotor in whole blood- {1-hematocrit}]*[Concentration of voxelotor in plasma/hematocrit])/5000*100.	15 days
Part B: Percentage of Days With SCD Symptom Exacerbation During the First 24 Weeks of Treatment	SCD symptoms were measured using the Patient Reported Outcome (PRO), Sickle Cell Disease Severity Measure (SCDSM) which was a self-administered 9-item questionnaire of SCD core symptoms including pain severity, frequency, and type, as well as fatigue and mental acuity, on a 4-point response scale that was completed daily using a handheld electronic device by the participants.	From Day 1 up to 24 weeks
Part B: Change From Baseline to Week 21 to 24 in the Sickle Cell Disease Severity Measure (SCDSM) Total Symptom Score (TSS)	The SCDSM was a self-administered 9-item questionnaire of SCD core symptoms including pain severity, frequency, and type, as well as fatigue and mental acuity, on a 4-point response scale with a range of 0 (strongly disagree) to 4 (strongly agree) that was completed daily using a handheld electronic device by the participants. TSS was calculated as the sum of the 9-item questionnaire scores scaled to a 100-point scale with a range of 0 (no symptoms) to 100 (most severe symptoms). Baseline TSS was the average of the non-missing score during the Screening period. The average of change from baseline in SCDSM TSS score for the 4-week period (Week 21 to 24) is reported.	Baseline, Weeks 21 to 24
Part B: Percent Change From Baseline to Weeks 12 and 24 in Lactate Dehydrogenase (LDH)		Baseline, Weeks 12 and 24
Part B: Percent Change From Baseline to Weeks 12 and 24 in Indirect Bilirubin		Baseline, Weeks 12 and 24
Part B: Percent Change From Baseline to Weeks 12 and 24 in Percentage Reticulocytes		Baseline, Weeks 12 and 24
Part B: Cmax of Voxelotor in Whole Blood and Plasma		Day 1 (pre-dose, 2, 8, 24 hours post-dose), pre-dose on Weeks 2, 4, 8, 12, 16, 20 and 24
Part B: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Whole Blood and Plasma	AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration and lambdaz is the elimination rate constant.	Day 1 (pre-dose, 2, 8, 24 hours post-dose), pre-dose on Weeks 2, 4, 8, 12, 16, 20 and 24
Part B: Terminal Elimination Half-life of Voxelotor for Plasma and Whole Blood	T1/2 was the time measured for the drug concentration to decrease by one half.	Day 1 (pre-dose, 2, 8, 24 hours post-dose), pre-dose on Weeks 2, 4, 8, 12, 16, 20 and 24
Part B: Accumulation Ratio (Rac) of Voxelotor for Plasma and Whole Blood	Accumulation ratio was calculated as ratio of area under the concentration-time curve from time 0 to 24 hours (AUC0-24) at steady-state (Day 28) to AUC0-24 on Day 1.	Day 1 (0 to 24 hours post-dose) and Day 28 (0 to 24 hours post-dose)
Part B: Percentage Hemoglobin Occupancy	Percentage hemoglobin occupancy (% Hb Occupancy) refers to the percentage of hemoglobin molecules within red blood cells that were bound to study drug. Concentration of voxelotor in whole blood and plasma was used to calculate %Hb occupancy. Percentage Hb occupancy within RBCs was estimated using the formula: ([Concentration of voxelotor in whole blood- {1-hematocrit}]*[Concentration of voxelotor in plasma/hematocrit])/5000*100.	Day 28
Part B: Change From Baseline to Week 12 and 24 in Cerebral Blood Flow	Cerebral blood flow was measured using TCD sonography. Change from baseline in cerebral blood flow as measured by TAMM TCD velocity is reported.	Baseline, Weeks 12 and 24
Part C: Change From Baseline to Weeks 24 and 48 in Hemoglobin Level		Baseline, Weeks 24 and 48
Part C: Percent Change From Baseline to Weeks 24 and 48 in LDH		Baseline, Weeks 24 and 48
Part C: Percent Change From Baseline to Weeks 24 and 48 in Indirect Bilirubin		Baseline, Weeks 24 and 48
Part C: Percent Change From Baseline to Weeks 24 and 48 in Percentage Reticulocytes		Baseline, Weeks 24 and 48
Part C: Change From Baseline to Week 24 in Cerebral Blood Flow	Cerebral blood flow was measured using TCD sonography. Change from baseline in cerebral blood flow as measured by TAMM TCD velocity is reported.	Baseline, Week 24
Part C: Time to Initial Hemoglobin Response	Time to initial Hb response was defined as the time from first dose of study treatment to the first occurrence of a change from baseline in Hb > 1 gram per deciliter (g/dL).	From first dose of study treatment (Day 1) up to Week 48
Part C: Cmax of Voxelotor for Plasma and Whole Blood		Day 1 (15 minutes to 2 hours post-dose), pre-dose on Weeks 4, 8, 12, 16, 20, 24, 36 and 48
Part C: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Whole Blood and Plasma	AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration and lambdaz is the elimination rate constant.	Day 1 (15 minutes to 2 hours post-dose), pre-dose on Weeks 4, 8, 12, 16, 20, 24, 36 and 48
Part C: Terminal Elimination Half-life (T1/2) of Voxelotor for Whole Blood and Plasma	T1/2 was the time measured for the drug concentration to decrease by one half.	Day 1 (15 minutes to 2 hours post-dose), pre-dose on Weeks 4, 8, 12, 16, 20, 24, 36 and 48
Part C: Percentage Hemoglobin Occupancy of Voxelotor	Percentage hemoglobin occupancy (% Hb Occupancy) refers to the percentage of hemoglobin molecules within red blood cells that were bound to study drug. Concentration of voxelotor in whole blood and plasma was used to calculate %Hb occupancy. Percentage Hb occupancy within RBCs was estimated using the formula: ([Concentration of voxelotor in whole blood- {1-hematocrit}]*[Concentration of voxelotor in plasma/hematocrit])/5000*100.	Day 28
Part C: Percentage of Participants With Normal Transcranial Doppler (TCD) Flow Velocity at Week 48	Normal TCD flow velocity was considered as < 170 centimeter per second (cm/sec) by non-imagining TCD or < 155 cm/sec by imaging transcranial Doppler (TCDi). Percentage of participants with normal TCD flow velocity at Week 48 by Baseline TCD group (i.e. Baseline normal TCD [<170 cm/sec] and Baseline conditional TCD [>=170 cm/sec] is reported.	Week 48
Part C: Annualized Incidence Rate of Vaso-occlusive Crisis (VOC) Events	VOC events included preferred terms of sickle cell anaemia with crisis, acute chest syndrome, pneumonia necrotising and pneumonia. Annualized incidence rate was calculated as total number of events divided by total person years. Total person years=sum of participants treatment period in years, which covered the time from first dose to last dose.	Up to Week 48
Part C: Annualized Incidence Rate of Stroke Events	Annualized incidence rate was calculated as total number of events divided by total person years. Total person years=sum of participants treatment period in years, which covered the time from first dose to last dose.	Up to Week 48
Part D: Cmax of Voxelotor for Plasma and Whole Blood		Day 1 (anytime between 15 minutes to 2 hours post-dose), pre-dose on Weeks 2, 8, 12, 16, 24, 36 and 48
Part D: Area Under the Concentration-Time Curve (AUC) From Time 0 Extrapolated to Infinity (AUC0-inf) of Voxelotor for Plasma and Whole Blood	AUC0-inf was calculated as AUCt + Ct/lambdaz, where AUCt=area under the concentration-time curve at designated time, Ct is the last quantifiable concentration and lambdaz is the elimination rate constant.	Day 1 (anytime between 15 minutes to 2 hours post-dose), pre-dose on Weeks 2, 8, 12, 16, 24, 36 and 48
Part D: T1/2 of Voxelotor for Plasma and Whole Blood	T1/2 was the time measured for the drug concentration to decrease by one half.	Day 1 (anytime between 15 minutes to 2 hours post-dose), pre-dose on Weeks 2, 8, 12, 16, 24, 36 and 48
Part D: Percentage Hemoglobin Occupancy	Percentage hemoglobin occupancy (% Hb Occupancy) refers to the percentage of hemoglobin molecules within red blood cells that were bound to study drug. Concentration of voxelotor in whole blood and plasma was used to calculate %Hb occupancy. Percentage Hb occupancy within RBCs was estimated using the formula: ([Concentration of voxelotor in whole blood- {1-hematocrit}]*[Concentration of voxelotor in plasma/hematocrit])/5000*100.	Day 28
Part D: Change From Baseline to Weeks 24 and 48 in Hemoglobin Level		Baseline, Weeks 24 and 48
Part D: Percent Change From Baseline to Weeks 24 and 48 in LDH		Baseline, Weeks 24 and 48
Part D: Percent Change From Baseline to Weeks 24 and 48 in Indirect Bilirubin		Baseline, Weeks 24 and 48
Part D: Percent Change From Baseline to Weeks 24 and 48 in Reticulocytes Count		Baseline, Weeks 24 and 48
Part D: Time to Initial Hemoglobin Response	Time to initial Hb response, defined as the time from first dose of study treatment to the first occurrence of a change from baseline in Hb > 1 g/dL.	From first dose of study treatment (Day 1) up to Week 48
Part D: Annualized Incidence Rate of VOC Events	VOC events included preferred terms of 'Sickle cell anemia with crisis', 'Acute chest syndrome', 'Pneumonia necrotising,' and 'Pneumonia. Annualized incidence rate was calculated as total number of events divided by total person years. Total person years=sum of participants treatment period in years, which covered the time from first dose to last dose.	Up to Week 48
Part D: Annualized Incidence Rate of Stroke Events	Annualized incidence rate was calculated as total number of events divided by total person years. Total person years=sum of participants treatment period in years, which covered the time from first dose to last dose.	Up 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 (Actual): October 2, 2023
• Study Completion (Actual): October 2, 2023

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 (Estimated): August 15, 2025
• Last Update Submitted That Met QC Criteria: August 13, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; 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