Sickle Cell DiseasePhase 4NCT05228821
Voxelotor Brain Oxygenation and Neurocognitive Study
A Phase 4 study testing Voxelotor Oral Tablet in people with Sickle Cell Disease, run by Pfizer at 2 sites in United States.
Trial summary
This is an open label, single arm multicenter trial to evaluate the effect of voxelotor treatment on cerebral blood flow (CBF) and neurocognitive function in adolescent and young adult participants (12-30 years of age) with sickle cell disease (SCD). Read more about this study
- Who is it for?
- Ages 12 to 30 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Voxelotor Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 2 sitesUnited States
- Study dates
- 9 Aug 2023to 23 Aug 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 12 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Male or female participants with confirmed diagnosis of SCD with HbSS or Hbβ0 thalassemia genotype. Documentation of SCD genotype is required and may be based on documented history of laboratory testing or confirmed by laboratory testing during Screening.
- Aged 12 to 30 years.
- Screening Hb level ≥ 5.5 and ≤ 10.5 g/dL.
- Must meet site-specific compliance requirements for a diagnostic MRI scan.
- Able to answer NIH Toolbox Module questions in English
- If participant is receiving hydroxyurea (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.
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- 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.
- 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.
- Written informed consent (≥ 18 years) or parental/guardian consent and participant assent (≥ 12-17 years) per Institutional Review Board (IRB) policy and requirements, consistent with ICH guidelines.
- Capable of complying with the requirements and restrictions in the protocol, and willing to participate in the study.
Who cannot join
- History of overt stroke including hemorrhagic stroke, transient ischemic attacks, or spinal cord injury.
- Grade 4 vasculopathy defined as moderate stenosis (50% to 69%) in more than 2 major cerebral arteries or severe stenosis (> 70%) in any major cerebral artery.
- Non-MRI compatible metal hardware and/or metal braces.
- 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.
- Participant is taking or has received crizanlizumab (Adakveo®) within 90 days prior to the Screening Visit.
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- Vaso-occlusive event requiring intravenous opioids within 28 days prior to Day 1.
- 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).
- Surgery within 8 weeks before Day 1 or planned elective surgery during the study.
- Anemia due to bone marrow failure (eg, myelodysplasia).
- Absolute reticulocyte count (ARC) < 100 × 10^9/L.
- Screening alanine aminotransferase or aspartate aminotransferase > 4× upper limit of normal (ULN).
- Severe renal dysfunction (estimated glomerular filtration rate [eGFR] <45 mL/min/1.73 m^2) or on chronic dialysis.
- Clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy
- Acute bacterial infection requiring antibiotic use should delay Screening/enrollment until the course of antibiotic therapy has been completed.
- Known active hepatitis A, B, or C or 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 CYP3A4 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 (particularly the MRI scan).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Washington University School of Medicine
St Louis, Missouri, 63110
The Children's Hospital at Montefiore
The Bronx, New York, 10467
About this study
Official title: An Open Label, Single Arm, Multicenter Study to Evaluate the Effect of Voxelotor on Cerebral Blood Flow and Neurocognitive Function in Adolescents and Adults With Sickle Cell Disease
This is an open label, single arm multicenter trial to evaluate the effect of voxelotor treatment on cerebral blood flow (CBF) and neurocognitive function in adolescent and young adult participants (12-30 years of age) with sickle cell disease (SCD).
Read the detailed description
Eligible participants will receive daily treatment with 1500 mg voxelotor for 24 weeks. During screening, at 12 and 24 weeks, participants will undergo an MRI for evaluation of cerebral blood flow and oxygen extraction fraction as well as NIH toolbox testing for evaluation of executive function, processing speed, and nonexecutive function.
- Conditions
- Sickle Cell Disease
- Being tested
- Voxelotor Oral Tablet
- 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 Oral TabletDrug
Also called Oxbryta
During the Treatment Period, participants will receive 1500 mg of voxelotor once daily (administered as tablets) for 24 weeks in addition to ongoing current standard of care (SOC) treatment
| Study group | Role | What they receive |
|---|---|---|
| Active Drug | Experimental | Generic Name: Voxelotor Dosage Form: tablet Dosage: 1500mg Frequency: QD Duration: 24 weeks Receives: Drug: Voxelotor Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in CBF
Change from Baseline in CBF through Week 24 measured by magnetic resonance imaging (MRI) using pseudo-continuous arterial spin labeling (pCASL).
Measured: Baseline to Week 24
Secondary outcomes (3)
Change in executive functioning.
Change from Baseline through Week 24 in the executive cognitive abilities composite score (using Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test, and List Sorting Test) as assessed by the National Institutes of Health Toolbox Cognition Module.
Measured: Baseline to Week 24
Change in processing speed
Change from Baseline through Week 24 in processing speed (using Pattern Comparison Test) as assessed by the NIH Toolbox Cognition Module
Measured: Baseline to Week 24
Change in nonexecutive functioning
Change from Baseline through Week 24 in nonexecutive cognitive abilities composite score (using Picture Vocabulary Test, Oral Reading Recognition Test, and Picture Sequence Memory Test) as assessed by the NIH Toolbox Cognition Module.
Measured: Baseline to Week 24
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 start9 Aug 2023
- Primary completion23 Aug 2023
- Study completion23 Aug 2023
Why it stopped: The study has been stopped due to Sponsor's business reasons. The termination is not a result of any safety concerns or change in the benefit-risk ratio.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 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
- NCT05228821
- Sponsor's protocol ID
- GBT440-043
- Other IDs
- C5341027
- Status last verified
- Aug 2024
- First submitted
- 10 Jan 2022
- Last updated
- 9 Aug 2024
- Results posted
- No
- 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 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Single Arm, Multicenter Study to Evaluate the Effect of Voxelotor on Cerebral Blood Flow and Neurocognitive Function in Adolescents and Adults With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT05228821
- Acronym / sponsor ID
- GBT440-043
- Conditions
- Sickle Cell Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study has been stopped due to Sponsor's business reasons. The termination is not a result of any safety concerns or change in the benefit-risk ratio.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 9 Aug 2023 (actual)
- Primary completion
- 23 Aug 2023 (actual)
- Study completion
- 23 Aug 2023 (actual)
- First posted
- 8 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an open label, single arm multicenter trial to evaluate the effect of voxelotor treatment on cerebral blood flow (CBF) and neurocognitive function in adolescent and young adult participants (12-30 years of age) with sickle cell disease (SCD).
Detailed description
Eligible participants will receive daily treatment with 1500 mg voxelotor for 24 weeks. During screening, at 12 and 24 weeks, participants will undergo an MRI for evaluation of cerebral blood flow and oxygen extraction fraction as well as NIH toolbox testing for evaluation of executive function, processing speed, and nonexecutive function.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Active Drug | Experimental | Drug: Voxelotor Oral TabletGeneric Name: Voxelotor Dosage Form: tablet Dosage: 1500mg Frequency: QD Duration: 24 weeks |
Who may qualify
- Ages
- 12 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- Male or female participants with confirmed diagnosis of SCD with HbSS or Hbβ0 thalassemia genotype. Documentation of SCD genotype is required and may be based on documented history of laboratory testing or confirmed by laboratory testing during Screening.
- Aged 12 to 30 years.
- Screening Hb level ≥ 5.5 and ≤ 10.5 g/dL.
- Must meet site-specific compliance requirements for a diagnostic MRI scan.
- Able to answer NIH Toolbox Module questions in English
Key exclusion criteria (22 listed)
- History of overt stroke including hemorrhagic stroke, transient ischemic attacks, or spinal cord injury.
- Grade 4 vasculopathy defined as moderate stenosis (50% to 69%) in more than 2 major cerebral arteries or severe stenosis (> 70%) in any major cerebral artery.
- Non-MRI compatible metal hardware and/or metal braces.
- 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 Oral TabletAlso: OxbrytaDuring the Treatment Period, participants will receive 1500 mg of voxelotor once daily (administered as tablets) for 24 weeks in addition to ongoing current standard of care (SOC) treatment | Drug | Active Drug |
Primary outcome
Change in CBF
Time frame: Baseline to Week 24
Change from Baseline in CBF through Week 24 measured by magnetic resonance imaging (MRI) using pseudo-continuous arterial spin labeling (pCASL).
3 secondary outcomes
Change in executive functioning.
Time frame: Baseline to Week 24
Change in processing speed
Time frame: Baseline to Week 24
Change in nonexecutive functioning
Time frame: Baseline to Week 24
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
- 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
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Voxelotor Oral Tablet in people with Sickle Cell Disease, run by Pfizer at 2 sites 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 11 inclusion and 22 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: withdrawn, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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 in CBF (time frame: Baseline to Week 24). 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 9 Aug 2024.