Sickle Cell DiseasePhase 3NCT05228834
Voxelotor Neurocognitive Function Study
A Phase 3 study testing Voxelotor Only Product in Oral Dose Form in people with Sickle Cell Disease, run by Pfizer at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 8 to 18 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Voxelotor Only Product in Oral Dose Form
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jun 2022to 30 Sep 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
- Aged 8 to < 18 years.
- Screening Hb level 5.5 to 10.5 g/dL.
- Able to answer NIH Toolbox Module questions validated and normed based on age and maternal education on tablet.
- 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.
- 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.
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- 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.
- Females of child-bearing potential must have a negative pregnancy test before the administration of study drug.
- 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.
- Capable of complying with the requirements and restrictions in the protocol, and willing to participate in the study.
Who cannot join
- Receiving chronic transfusion therapy.
- 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).
- 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.
- 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.
- Participant is taking or has received voxelotor (Oxbryta®) within 90 days prior to the Screening Visit.
- Surgery within 8 weeks before Day 1 or planned elective surgery during the study.
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- Anemia due to bone marrow failure (eg, myelodysplasia).
- Absolute reticulocyte count (ARC) < 100 × 10^9/L.
- Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 4× upper limit of normal (ULN).
- Severe renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m^2) or is on chronic dialysis.
- Clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy.
- Patients with acute bacterial infection requiring antibiotic use should delay screening /enrollment until the course of antibiotic therapy has been completed.
- Patients with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive.
- Symptomatic coronavirus disease of 2019 (COVID-19) infection.
- Females who are breast-feeding or pregnant.
- History of hematopoietic stem cell transplant or gene therapy.
- Participants taking concomitant medications such as sensitive cytochrome P450 (CYP)3A4 substrates with a narrow therapeutic range, or strong CYP3A4 inducers
- 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).
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Maryland Medical Center
Baltimore, Maryland, 21201
About this study
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
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.
Read the detailed 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.
- Conditions
- Sickle Cell Disease
- Being tested
- Voxelotor Only Product in Oral Dose Form, Placebo
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Voxelotor Only Product in Oral Dose FormDrug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Active Drug | Experimental | Voxelotor 1500mg or equivalent daily as a tablet or powder for oral suspension Receives: Drug: Voxelotor Only Product in Oral Dose Form |
| Placebo | Placebo comparator | Matching Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (last assessment prior to first dose of study treatment), Week 12
Secondary outcomes (8)
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.
Measured: Baseline (last assessment prior to first dose of study treatment), Week 12
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.
Measured: Baseline (last assessment prior to first dose of study treatment) up to Week 12
Change From Baseline in Hemoglobin Level Up to Week 12
Measured: Baseline (last assessment prior to first dose of study treatment) up to Week 12
Change From Baseline in Absolute Reticulocyte Count Up to Week 12
Measured: Baseline (last assessment prior to first dose of study treatment) up to Week 12
Change From Baseline in Percentage Reticulocyte Up to Week 12
Measured: Baseline (last assessment prior to first dose of study treatment) up to Week 12
Change From Baseline in Lactate Dehydrogenase (LDH) Up to Week 12
Measured: Baseline (last assessment prior to first dose of study treatment) up to Week 12
Change From Baseline in Unconjugated Bilirubin Up to Week 12
Measured: Baseline (last assessment prior to first dose of study treatment) up to Week 12
Percent Change From Baseline in Unconjugated Bilirubin, Absolute Reticulocyte, Percentage Reticulocytes, Lactate Dehydrogenase (LDH) Up to Week 12
Measured: Baseline (last assessment prior to first dose of study treatment) up to Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2022
- Study start24 Jun 2022
- Primary completion30 Sep 2022
- Study completion30 Sep 2022
Why it stopped: Data will not inform further development of Voxelotor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05228834
- Sponsor's protocol ID
- GBT440-044
- Other IDs
- C5341028
- Status last verified
- Mar 2024
- First submitted
- 10 Jan 2022
- Last updated
- 2 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05228834
- Acronym / sponsor ID
- GBT440-044
- Conditions
- Sickle Cell Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Data will not inform further development of Voxelotor
- Enrolment
- 1 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 24 Jun 2022 (actual)
- Primary completion
- 30 Sep 2022 (actual)
- Study completion
- 30 Sep 2022 (actual)
- First posted
- 8 Feb 2022 (actual)
- Results
- Posted 2 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Drug | Experimental | Drug: Voxelotor Only Product in Oral Dose FormVoxelotor 1500mg or equivalent daily as a tablet or powder for oral suspension |
| Placebo | Placebo comparator | Drug: PlaceboMatching Placebo |
Who may qualify
- Ages
- 8 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- 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.
- Aged 8 to < 18 years.
- Screening Hb level 5.5 to 10.5 g/dL.
- Able to answer NIH Toolbox Module questions validated and normed based on age and maternal education on tablet.
- 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.
Key exclusion criteria (19 listed)
- Receiving chronic transfusion therapy.
- 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).
- 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.
- 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.
- Participant is taking or has received voxelotor (Oxbryta®) within 90 days prior to the Screening Visit.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Voxelotor Only Product in Oral Dose FormDuring 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. | Drug | Active Drug |
| PlaceboDuring 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. | Drug | Placebo |
Primary outcome
Change From Baseline in Executive Abilities Composite Score Assessed Using NIH Toolbox Cognition Module At Week 12
Time frame: Baseline (last assessment prior to first dose of study treatment), 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.
8 secondary outcomes
Change From Baseline in Pattern Comparison Processing Speed Test Scores Assessed Using NIH Toolbox Cognition Module at Week 12
Time frame: Baseline (last assessment prior to first dose of study treatment), Week 12
Change From Baseline in Nonexecutive Cognitive Abilities Composite Score Assessed Using NIH Toolbox Cognition Module Up to Week 12
Time frame: Baseline (last assessment prior to first dose of study treatment) up to Week 12
Change From Baseline in Hemoglobin Level Up to Week 12
Time frame: Baseline (last assessment prior to first dose of study treatment) up to Week 12
Change From Baseline in Absolute Reticulocyte Count Up to Week 12
Time frame: Baseline (last assessment prior to first dose of study treatment) up to Week 12
Change From Baseline in Percentage Reticulocyte Up to Week 12
Time frame: Baseline (last assessment prior to first dose of study treatment) up to Week 12
Change From Baseline in Lactate Dehydrogenase (LDH) Up to Week 12
Time frame: Baseline (last assessment prior to first dose of study treatment) up to Week 12
Change From Baseline in Unconjugated Bilirubin Up to Week 12
Time frame: Baseline (last assessment prior to first dose of study treatment) up to Week 12
Percent Change From Baseline in Unconjugated Bilirubin, Absolute Reticulocyte, Percentage Reticulocytes, Lactate Dehydrogenase (LDH) Up to Week 12
Time frame: Baseline (last assessment prior to first dose of study treatment) up to Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Voxelotor Only Product in Oral Dose Form in people with Sickle Cell Disease, run by Pfizer at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Executive Abilities Composite Score Assessed Using NIH Toolbox Cognition Module At Week 12 (time frame: Baseline (last assessment prior to first dose of study treatment), Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 May 2024.