- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04247594
Dose Escalation Study to Evaluate the Safety, Tolerability, PK and PD of Voxelotor in Patients With SCD
November 1, 2023 updated by: Pfizer
A Phase 2, Open Label, Multiple Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Voxelotor in Patients With Sickle Cell Disease
Study participants will undergo up to four periods of voxelotor administered orally at progressively higher dose levels from 1500 mg until either a maximum tolerated dose (MTD) or 3000 mg/day dose is reached, whichever occurs first
Study Overview
Study Type
Interventional
Enrollment (Actual)
6
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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-
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London, United Kingdom
- King's College Hospital
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London, United Kingdom
- Guy's and St Thomas' NHS Foundation Trust
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London, United Kingdom
- Hammersmith Hospital
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London, United Kingdom
- Guy's Hospital
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London, United Kingdom
- Homerton University
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London, United Kingdom
- Royal London Hospital, Barts Health NHS Trust
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 60 years (Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Male or female with SCD
- Documentation of SCD genotype HbSS or HbSB0
- Age 18 to < 60 years, inclusive
- Hemoglobin ≥ 5.5 and ≤ 10.5 g/dL during Screening, and considered stable and close to Baseline by the Investigator
- For participants taking HU, the dose in mg/kg must be stable for at least 90 days prior to signing the informed consent form (ICF) and with no anticipated need for dose adjustments during the study, in the opinion of the Investigator.
- Participants, who if female and of child-bearing potential, agree to use highly effective methods of contraception or practicing abstinence from study start to 30 days after the last dose of study drug, and who if male, agree to use barrier methods of contraception or practice abstinence from study start to 30 days after the last dose of study drug
- Participant has provided documented informed consent
Exclusion Criteria:
- More than 10 VOCs within 12 months of screening that required a hospital, emergency room, or clinic visit
- Female participant who is breast feeding or pregnant
- Receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or have received an RBC transfusion for any reason within 60 days of signing the ICF or at any time during the Screening Period
- Hospitalized for sickle cell crisis or other vaso-occlusive event within 30 days prior to dosing (ie, a vaso-occlusive event cannot be within 30 days prior to dosing)
- Screening laboratory test of alanine aminotransferase (ALT) > 4 × upper level of normal (ULN)
- Clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy, including acute bacterial infection requiring antibiotics
- Known to be COVID-19 positive from within 3 weeks of screening through Day 1
- Participants with active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive
- Severe renal dysfunction (estimated glomerular filtration rate < 30 mL/min/1.73 m2 at the Screening visit; calculated by the local laboratory to assess safety) or is on chronic dialysis
- History of malignancy within the past 2 years prior to treatment Day 1 requiring chemotherapy and/or radiation (with the exception of local therapy for non-melanoma skin malignancy)
History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:
- Unstable angina pectoris or myocardial infarction or elective coronary intervention
- Congestive heart failure requiring hospitalization
- Uncontrolled clinically significant arrhythmias
- Pulmonary hypertension
Criteria related to ECG parameters:
- PR interval > 220 msec in any participant
- QRS interval > 120 msec or QT interval corrected using Fridericia's formula (QTcF) > 480 msec (both genders) in participants without bundle branch block
- QRS interval > 120 msec in participants with newly (within 3 months) emerged bundle branch block
- A participant with stable bundle branch block with or without stable cardiac disease may be enrolled; QRS interval > 120 msec and QTcF interval > 480 msec are acceptable in these participants.
- Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable)
- Participated in another clinical trial of an investigational agent 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 agent or medical device
- Inadequate venous access as determined by the Investigator/site staff
- Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent
- Received erythropoietin or other hematopoietic growth factor treatment within 28 days of signing ICF or is anticipated to require such agents during the study
- Ongoing or recent (within 2 years) substance abuse
- Known allergy to voxelotor
- Use of herbal medications (eg, St. John's Wort), sensitive cytochrome P450 (CYP) 3A4 substrates with a narrow therapeutic index, strong CYP3A4 inhibitors, fluconazole, or moderate or strong CYP3A4 inducers
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Period 1
1500 mg per day
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synthetic small molecule supplied as 500 mg tablets
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Experimental: Period 2
2000 mg per day
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synthetic small molecule supplied as 500 mg tablets
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Experimental: Period 3
2500 mg per day
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synthetic small molecule supplied as 500 mg tablets
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Experimental: Period 4
3000 mg per day
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synthetic small molecule supplied as 500 mg tablets
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Treatment-emergent Adverse Events (AEs)
Time Frame: approximately 300 days
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Treatment emergent AEs including SAEs
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approximately 300 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Clinically Significant Abnormalities in Hb, Unconjugated Bilirubin, % Reticulocyte, Absolute Reticulocyte, and Lactate Dehydrogenase [LDH]
Time Frame: approximately 200 days
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approximately 200 days
|
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Number of Participants With an Hb Increase > 1 g/dL Compared to Baseline
Time Frame: approximately 200 days
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Participants with an Hb increase > 1 g/dL compared to Baseline.
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approximately 200 days
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Incidence Rate of VOCs
Time Frame: approximately 200 days
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Incidence rate of vaso-occlusive crisis
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approximately 200 days
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 9, 2020
Primary Completion (Actual)
June 8, 2021
Study Completion (Actual)
June 8, 2021
Study Registration Dates
First Submitted
January 21, 2020
First Submitted That Met QC Criteria
January 28, 2020
First Posted (Actual)
January 30, 2020
Study Record Updates
Last Update Posted (Actual)
November 21, 2023
Last Update Submitted That Met QC Criteria
November 1, 2023
Last Verified
October 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- GBT440-029
- C5341042 (Other Identifier: Alias Study Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
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.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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