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

Sickle Cell Disease Clinical Trial

— HOPE Kids 2  

Official title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Voxelotor (GBT440) in Pediatric Participants With Sickle Cell Disease (HOPE Kids 2)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04218084
• Other study ID #: GBT440-032
• Secondary ID: C53410212017-000
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 11, 2020
• Est. completion date: January 28, 2025

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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 study will be conducted at approximately 50 international clinical sites, and will enroll approximately 224 participants. Participants will be randomized in a 1:1 ratio to receive voxelotor or placebo. All participants younger than 12 years of age and randomized to voxelotor will receive a dose based on their body weight, to provide exposure corresponding to the adult dose of 1500 mg/day.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 236
• Est. completion date: January 28, 2025
• Est. primary completion date: August 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 14 Years

Eligibility

Inclusion Criteria:

1. Male or female participants with Sickle Cell Anemia (SCA) HbSS, HbSß0 thalassemia genotype

2. TCD time averaged maximum of the mean velocity (TAMMV) arterial cerebral blood flow = 170 to 200cm/sec during the Screening Period

3. Hb = 5.5 and = 10.5 g/dL during screening

4. 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

5. Written informed parental/guardian consent and participant assent (where applicable) has been obtained per IRB/EC policy and requirements, consistent with ICH guidelines.

Exclusion Criteria:

1. Body weight < 10kg at the screening visit

2. Hospitalization for VOC or acute chest syndrome (ACS) within the 14 days prior to execution of informed consent/assent

3. More than 10 VOCs within the past 12 months that required hospitalization, emergency room, or clinic visit

4. Stroke resulting in focal neurological deficit; previous silent infarcts are permitted.

5. Known history or findings suggestive of significant cerebral vasculopathy

6. History of seizure disorder

7. 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

8. 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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• Voxelotor
Participants are randomized 1:1 to receive voxelotor or placebo.
• Placebo
Matching placebo.

Locations

Country	Name	City	State
Egypt	Alexandria Clinical Research Center, Faculty of Medicine, Alexandria University	Alexandria
Egypt	Abu El Rich Hospital, Cairo University Hospital	Cairo
Egypt	Abu Elrish Children Hospital	Cairo
Egypt	Ain Shams University Hospital- Clinical Research Center (MASRI)	Cairo	Abassia
Egypt	Egyptian Thalassemia Association (satellite site)	Cairo
Egypt	Zagazig University Hospital	Zagazig	Alsharkia
France	AP-HP Hopital Robert Debré	Paris
Ghana	Department of Child Health, University of Ghana Medical School, College of Health Sciences, Korle-Bu	Accra	Greater Accra
Ghana	Komfo Anokye Teaching Hospital	Kumasi	Ashanti
Italy	Azienda Ospedaliera Universitaria Meyer "A.O.U. Meyer" - SOC "Oncologia, Ematologia e TCSE"	Firenze
Italy	Azienda Ospedaliera Universitaria (A.O.U.) "Luigi Vanvitelli"	Napoli
Italy	Azienda Ospedaliera Universita' (AOU ) Padova	Padova
Italy	Azienda Ospedaliera Universita' (AOU) Padova	Padova
Kenya	Kemri/Crdr,Siaya,Kemri Clinical Research Annex	Kisumu	Siaya
Kenya	Gertrude's Children Hospital	Nairobi
Kenya	KEMRI CRDR Clinical Research Annex	Nairobi
Kenya	Strathmore University Medical Centre	Nairobi
Nigeria	University of Nigeria Teaching Hospital	Enugu
Nigeria	College of Medicine, University of Ibadan	Ibadan	OYO State
Nigeria	Barau Dikko Teaching/Kaduna State University	Kaduna
Nigeria	Aminu Kano Teaching Hospital	Kano
Nigeria	Lagos University Teaching Hospital	Surulere	Lagos
Oman	Sultan ?Qaboos University Hospital	Muscat
Oman	Sultan Qaboos University Hospital	Muscat
Saudi Arabia	King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard - Health	Riyadh
Saudi Arabia	King Saud University Medical City	Riyadh
United Kingdom	Barts Health NHS Trust	London
United Kingdom	King's College Hospital NHS Foundation Trust	London
United States	Children's Healthcare of Atlanta AFLAC Center	Atlanta	Georgia
United States	Children's Healthcare of Atlanta: Hughes Spalding	Atlanta	Georgia
United States	Children's Healthcare of Atlanta: Scottish Rite	Atlanta	Georgia
United States	Children's of Alabama	Birmingham	Alabama
United States	Boston Childien's Hospital - Clinical Research Pharmacy	Boston	Massachusetts
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Boston Children's Hospital - Clinical Research Pharmacy	Boston	Massachusetts
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Medical University of South Carolina: Investigational Drug Services	Charleston	South Carolina
United States	Medical University of South Carolina: Shawn Jenkins Women's and Children's Hospital	Charleston	South Carolina
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Texas Children's Hospital	Houston	Texas
United States	Texas Children's Hospital - Investigational Pharmacy	Houston	Texas
United States	Texas Children's Hospital- Wallace Tower	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	St. Jude Children's Research Hospital - Pharmaceutical Services	Memphis	Tennessee
United States	University of Miami	Miami	Florida
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Egypt,  France,  Ghana,  Italy,  Kenya,  Nigeria,  Oman,  Saudi Arabia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TCD Measurement	The change in time averaged maximum of the mean velocity (TAMMV) arterial cerebral blood flow, as measured by TCD.	24 weeks
Secondary	Change in TCD Flow Velocity		48 and 96 weeks
Secondary	Time to Conversion to Abnormal TCD Flow Velocity	Time to conversion to abnormal TCD flow velocity (= 200 cm/sec)	24, 48, and 96 weeks
Secondary	Time to Reversion to Normal TCD Flow Velocity	Time to reversion to normal TCD flow velocity (<170 cm/sec)	24, 48, and 96 weeks
Secondary	TCD Flow Velocity Reduction	Proportion of participants with TCD flow velocity reduction = 15 cm/sec	24, 48, and 96 weeks
Secondary	Number of Participants with Change in Hemoglobin (Hb) from baseline		baseline, 24, 48, and 96 weeks
Secondary	Change in Unconjugated Bilirubin from baseline		baseline, 24, 48 and 96 weeks
Secondary	Change in Percent of Reticulocyte from baseline		baseline, 24, 48, and 96 weeks
Secondary	Change in Absolute Reticulocyte from baseline		baseline, 24, 48, and 96 weeks
Secondary	Change in Lactate Dehydrogenase (LDH) from baseline		baseline, 24, 48, and 96 weeks
Secondary	Annualized incidence rate of vaso-occlusive crises (VOCs)		96 weeks

External Links

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