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

NCT02850406 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: GBT440-007C5341020
• Study Type: interventional
• Target: 147
• Locations: 3 countries
• Sites: 20

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.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (48)

• 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

  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

  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

  pre-dose, 2, 8, 24, 48, 96, 168 and 336 hours post-dose

Study Arms (1)

Voxelotor

EXPERIMENTAL

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

Interventions

Voxelotor DRUG

* 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

Voxelotor

Eligibility Criteria

• Age: 6 Months - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (20)

Brentwood Clinic UCSF Benioff Children's Hospital Oakland

Brentwood, California, 94513, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta Scottish Rite

Atlanta, Georgia, 30342, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

University of Illinois at Chicago Clinical Research Center

Chicago, Illinois, 60612, United States

Location

Our Lady of the Lake Children's Hospital (IP Address)

Baton Rouge, Louisiana, 70809, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Rutgers-Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08903, United States

Location

Brody School of Medicine at East Carolina University

Greenville, North Carolina, 27834, United States

Location

University Hospitals Cleveland Medical Center, Rainbow Babies & Children's Hospital

Cleveland, Ohio, 44106, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

American University of Beirut - Medical Center

Beirut, Lebanon

Location

Rafik Hariri University Hospital

Beirut, Lebanon

Location

Nini Hospital

Tripoli, Lebanon

Location

University College London Hospital, NHS Foundation Trust

London, Greater London, NW1 2PG, United Kingdom

Location

Barts Health NHS Trust, The Royal London Hospital

London, E1 1BB, United Kingdom

Location

Guy's and St Thoma's NHS Foundation Trust, Evelina London Children's Hospital

London, SE1 7EH, United Kingdom

Location

Manchester University NHS Foundation Trust, Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35451176 DERIVED

Related Links

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

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

voxelotor

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: July 1, 2016
• First Posted: August 1, 2016
• Study Start: July 5, 2016
• Primary Completion: October 2, 2023
• Study Completion: October 2, 2023
• Last Updated: August 15, 2025
• Results First Posted: August 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

US (13); LE (3); GB (4)