Voxelotor Neurocognitive Function Study

Sickle Cell Disease Clinical Trial

Official title:

A Phase 3b, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Treatment Effect of Voxelotor on Neurocognitive Function in Pediatric Participants 8 to < 18 Years of Age With Sickle Cell Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05228834
• Other study ID #: GBT440-044
• Secondary ID: C5341028
• Status: Terminated
• Phase: Phase 3
• Start date: June 24, 2022
• Est. completion date: September 30, 2022

Study information

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

Clinical Trial Summary

This is a Phase 3b, randomized, double-blind, placebo-controlled, multicenter study to assess the treatment effect of voxelotor on neurocognitive function as assessed by the National Institute of Health (NIH) Toolbox Cognition Module of executive abilities in pediatric participants (8 to < 18 years) with SCD.

Description:

Eligible participants will receive daily treatment with 1500 mg voxelotor or matching placebo for 12 weeks. During screening and at the end of 12 weeks participants will undergo a series of tests to measure the change in neurocognitive functions.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: September 30, 2022
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 18 Years

Eligibility

Inclusion Criteria:

1. Male or female participants with confirmed diagnosis of SCD (all genotypes). Documentation of SCD genotype is required and may be based on documented history of laboratory testing or confirmed by laboratory testing during Screening.

2. Aged 8 to < 18 years.

3. Screening Hb level 5.5 to 10.5 g/dL.

4. Able to answer NIH Toolbox Module questions validated and normed based on age and maternal education on tablet.

5. If participant is receiving HU they must have been on a stable dose for at least 90 days prior to signing the ICF/AF, with no dose modifications or initiation of HU planned or anticipated by the Investigator.

6. If participant is receiving erythropoiesis-stimulating agents (ESAs) they must have been on a stable dose for at least 12 weeks before enrollment with no dose modifications planned or anticipated by the Investigator.

7. Participants, who if female and of child-bearing potential, agree to use highly effective methods of contraception from study start to 30 days after the last dose of study drug and who if male, agree to use barrier methods of contraception and refrain from donating sperm from study start to 30 days after the last dose of study drug.

8. Females of child-bearing potential must have a negative pregnancy test before the administration of study drug.

9. Parental/guardian consent and participant assent (between = 12 and < 18 years) per Institutional Review Board (IRB)/Independent ethics committee (IEC) policy and requirements, consistent with International Council for Harmonisation (ICH) guidelines.

10. Capable of complying with the requirements and restrictions in the protocol, and willing to participate in the study.

Exclusion Criteria:

1. Receiving chronic transfusion therapy.

2. Red blood cell (RBC) transfusion within 3 months before initiation of study drug or receives scheduled RBC transfusion therapy (also termed chronic, prophylactic, or preventive transfusion).

3. History of overt stroke including hemorrhagic stroke or transient ischemic attack (TIA) or spinal cord injury, magnetic resonance angiography (MRA)-defined vasculopathy, or magnetic resonance imaging (MRI)/transcranial doppler (TCD)-documented silent cerebral infarcts.

4. Congenital brain malformation, previously diagnosed severe developmental disability (eg, autism and/or intelligence quotient [IQ] < 60, and/or severe attention deficit hyperactivity disorder [ADHD]), or impairment that would prevent the use of a computer tablet.

5. Participant is taking or has received voxelotor (Oxbryta®) within 90 days prior to the Screening Visit.

6. Surgery within 8 weeks before Day 1 or planned elective surgery during the study.

7. Anemia due to bone marrow failure (eg, myelodysplasia).

8. Absolute reticulocyte count (ARC) < 100 × 10^9/L.

9. Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 4× upper limit of normal (ULN).

10. Severe renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m^2) or is on chronic dialysis.

11. Clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy.

1. Patients with acute bacterial infection requiring antibiotic use should delay screening /enrollment until the course of antibiotic therapy has been completed.

2. Patients with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive.

12. Symptomatic coronavirus disease of 2019 (COVID-19) infection.

13. Females who are breast-feeding or pregnant.

14. History of hematopoietic stem cell transplant or gene therapy.

15. Participants taking concomitant medications such as sensitive cytochrome P450 (CYP)3A4 substrates with a narrow therapeutic range, or strong CYP3A4 inducers

16. Participated in another clinical trial of an investigational product (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational product (or medical device).

17. Medical, psychological, or behavioral condition that, in the opinion of the Investigator, would confound or interfere with evaluation of safety and/or efficacy of the study drug, prevent compliance with the study protocol; preclude informed consent; or, render the participant unable/unlikely to comply with the study procedures.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

Drug:
• Voxelotor Only Product in Oral Dose Form
During the Randomized Treatment Period, participants will be randomized in a 1:1 ratio to receive 1500 mg of voxelotor (or the weight-adjusted equivalent dose for participants < 12 years old), once daily (administered orally as tablets/PFOS) or matching placebo for 12 weeks in addition to ongoing standard of care (SOC) treatment.
• Placebo
During the Randomized Treatment Period, participants will be randomized in a 1:1 ratio to receive 1500 mg of voxelotor (or the weight-adjusted equivalent dose for participants < 12 years old), once daily (administered orally as tablets/PFOS) or matching placebo for 12 weeks in addition to ongoing standard of care (SOC) treatment.

Locations

Country	Name	City	State
United States	University of Maryland Medical Center	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event was defined as any untoward medical occurrence associated with the use of a drug in participants whether or not considered drug related. TEAEs were those events with onset dates that occurred during the treatment period.	From start of study treatment (Day 1) up to Week 12
Primary	Change From Baseline in Executive Abilities Composite Score Assessed Using NIH Toolbox Cognition Module At Week 12	The NIH toolbox cognition module is a standardized cognitive battery comprising of executive function, episodic memory, language, processing speed, working memory, and attention as subdomains. The toolbox is comprised of 7 test instruments that measure 8 abilities within 6 major cognitive domains and have been categorized as executive abilities (Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test, and List Sorting Test) and nonexecutive abilities (Picture Vocabulary Test, Oral Reading Recognition Test, and Picture Sequence Memory Test). The NIH toolbox standard score has a mean of 100 and standard deviation (SD) of 15. The higher the score, the better the performance.	Baseline (last assessment prior to first dose of study treatment), Week 12
Secondary	Change From Baseline in Pattern Comparison Processing Speed Test Scores Assessed Using NIH Toolbox Cognition Module at Week 12	The NIH Toolbox Cognition Battery Test is a comprehensive set of neuro behavioral measurements used to assess cognitive, sensory and motor functions where a higher composite score equals better cognitive performance. The NIH Toolbox Cognitive Scores used the Fully Adjusted Scale score (also referred to as the fully corrected T-score) with a mean of 50 and standard deviation of 10.	Baseline (last assessment prior to first dose of study treatment), Week 12
Secondary	Change From Baseline in Nonexecutive Cognitive Abilities Composite Score Assessed Using NIH Toolbox Cognition Module Up to Week 12	The NIH toolbox cognition module is a standardized cognitive battery comprising of executive function, episodic memory, language, processing speed, working memory, and attention as subdomains. The toolbox is currently comprised of 7 test instruments that measure 8 abilities within 6 major cognitive domains and have been categorized as executive abilities (Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test, and List Sorting Test) and nonexecutive abilities (Picture Vocabulary Test, Oral Reading Recognition Test, and Picture Sequence Memory Test). Baseline was defined as the last assessment performed prior to receiving the first dose of study treatment. The NIH toolbox standard score has a mean of 100 and SD of 15. The higher the score, the better the performance.	Baseline (last assessment prior to first dose of study treatment) up to Week 12
Secondary	Change From Baseline in Hemoglobin Level Up to Week 12		Baseline (last assessment prior to first dose of study treatment) up to Week 12
Secondary	Change From Baseline in Absolute Reticulocyte Count Up to Week 12		Baseline (last assessment prior to first dose of study treatment) up to Week 12
Secondary	Change From Baseline in Percentage Reticulocyte Up to Week 12		Baseline (last assessment prior to first dose of study treatment) up to Week 12
Secondary	Change From Baseline in Lactate Dehydrogenase (LDH) Up to Week 12		Baseline (last assessment prior to first dose of study treatment) up to Week 12
Secondary	Change From Baseline in Unconjugated Bilirubin Up to Week 12		Baseline (last assessment prior to first dose of study treatment) up to Week 12
Secondary	Percent Change From Baseline in Unconjugated Bilirubin, Absolute Reticulocyte, Percentage Reticulocytes, Lactate Dehydrogenase (LDH) Up to Week 12		Baseline (last assessment prior to first dose of study treatment) up to Week 12

External Links

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