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

NCT04218084 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: GBT440-0322017-000903-26C5341021
• Study Type: interventional
• Target: 236
• Locations: 9 countries
• Sites: 35

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.

Conditions

Sickle Cell Disease

Keywords

Sickle Cell Disease; Transcranial Doppler Ultrasound (TCD)

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Time-Averaged Maximum of Mean Velocity (TAMMV) Arterial Cerebral Blood Flow at Week 24

  TAMMV is an ultrasound measurement used in transcranial Doppler (TCD) to assess blood flow in cerebral arteries. TCD flow velocities were categorized as follows: (i) Normal: \< 170 centimeter per second (cm/sec); (ii) Conditional: 170 to \< 200 cm/sec - the eligible participant population for this study; (iii) Abnormal: \>= 200 cm/sec.

  Baseline (value at screening), Week 24

Secondary Outcomes (10)

• Change From Baseline in TAMMV Arterial Cerebral Blood Flow at Week 48

  Baseline (value at Screening), Weeks 48

• Time to Conversion to Abnormal TCD Flow

  Up to 96 weeks

• Time to Reversion to Normal TCD Flow

  Up to 96 weeks

• Percentage of Participants With TAMMV Reduced by >=15 cm/Sec From Baseline at Weeks 24, 48 and 96

  At Weeks 24, 48 and 96

• Change From Baseline in Hemoglobin (Hb) at Weeks 24, 48 and 96

  Baseline (value at Screening), Weeks 24, 48 and 96

Study Arms (2)

Voxelotor

EXPERIMENTAL

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

Drug: Voxelotor

Placebo

PLACEBO COMPARATOR

Matching placebo.

Drug: Placebo

Interventions

Voxelotor DRUG

Participants are randomized 1:1 to receive voxelotor or placebo.

Voxelotor

Placebo DRUG

Matching placebo.

Placebo

Eligibility Criteria

• Age: 2 Years - 14 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (35)

Children's National Medical Center

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

Location

University of Miami

Miami, Florida, 33136, United States

Location

Children's Healthcare of Atlanta: Hughes Spalding

Atlanta, Georgia, 30303, United States

Location

Boston Children's Hospital - Clinical Research Pharmacy

Boston, Massachusetts, 02115, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina: Investigational Drug Services

Charleston, South Carolina, 29425, United States

Location

Medical University of South Carolina: Shawn Jenkins Women's and Children's Hospital

Charleston, South Carolina, 29425, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Texas Children's Hospital - Investigational Pharmacy

Houston, Texas, 77030, United States

Location

Texas Children's Hospital- Wallace Tower

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Ain Shams University Hospital- Clinical Research Center (MASRI)

Cairo, Abassia, 11566, Egypt

Location

Zagazig University Hospital

Zagazig, Alsharkia, Egypt

Location

Alexandria Clinical Research Center, Faculty of Medicine, Alexandria University

Alexandria, 21131, Egypt

Location

Abu El Rich Hospital, Cairo University Hospital

Cairo, 11562, Egypt

Location

Komfo Anokye Teaching Hospital

Kumasi, Ashanti Region, 00233, Ghana

Location

Department of Child Health, University of Ghana Medical School, College of Health Sciences, Korle-Bu

Accra, Greater Accra Region, GA-221-1570, Ghana

Location

Azienda Ospedaliera Universitaria Meyer "A.O.U. Meyer" - SOC "Oncologia, Ematologia e TCSE"

Florence, 50139, Italy

Location

Azienda Ospedaliera Universitaria (A.O.U.) "Luigi Vanvitelli"

Naples, 80138, Italy

Location

Azienda Ospedaliera Universita' (AOU ) Padova

Padua, 35128, Italy

Location

Azienda Ospedaliera Universita' (AOU) Padova

Padua, 35128, Italy

Location

Kemri/Crdr,Siaya,Kemri Clinical Research Annex

Kisumu, Siaya County, 40600, Kenya

Location

KEMRI CRDR Clinical Research Annex

Nairobi, 00100, Kenya

Location

Strathmore University Medical Centre

Nairobi, 00200, Kenya

Location

Gertrude's Children Hospital

Nairobi, 100, Kenya

Location

Lagos University Teaching Hospital

Surulere, Lagos, 100254, Nigeria

Location

College of Medicine, University of Ibadan

Ibadan, Oyo State, 200212, Nigeria

Location

University of Nigeria Teaching Hospital

Enugu, 460000, Nigeria

Location

Barau Dikko Teaching/Kaduna State University

Kaduna, 800212, Nigeria

Location

Aminu Kano Teaching Hospital

Kano, 700233, Nigeria

Location

Sultan َQaboos University Hospital

Muscat, Oman

Location

King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard - Health

Riyadh, 11481, Saudi Arabia

Location

Barts Health NHS Trust

London, E1 1BB, United Kingdom

Location

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 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-Blind, Placebo-Controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: January 6, 2020
• Study Start: November 11, 2020
• Primary Completion: January 18, 2024
• Study Completion: November 6, 2024
• Last Updated: March 10, 2026
• Results First Posted: June 13, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

IT (4); EG (4); KE (4); GH (2); NG (5); US (13); SA (1); OM (1); GB (1)