Sickle Cell DiseasePhase 2NCT04247594
Dose Escalation Study to Evaluate the Safety, Tolerability, PK and PD of Voxelotor in Patients With SCD
A Phase 2 study testing Voxelotor in people with Sickle Cell Disease, run by Pfizer at 6 sites in United Kingdom.
Trial summary
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 Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Voxelotor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 6 sitesUnited Kingdom
- Study dates
- 9 Jan 2020to 8 Jun 2021
- Phase
- Phase 2
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United Kingdom6 sites
Guy's and St Thomas' NHS Foundation Trust
London
Guy's Hospital
London
Hammersmith Hospital
London
Homerton University
London
King's College Hospital
London
Royal London Hospital, Barts Health NHS Trust
London
About this study
Official title: 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
- Conditions
- Sickle Cell Disease
- Being tested
- Voxelotor
- Keywords
- Sickle Cell Disease, SCD
- 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.
VoxelotorDrug
synthetic small molecule supplied as 500 mg tablets
| Study group | Role | What they receive |
|---|---|---|
| Period 1 | Experimental | 1500 mg per day Receives: Drug: Voxelotor |
| Period 2 | Experimental | 2000 mg per day Receives: Drug: Voxelotor |
| Period 3 | Experimental | 2500 mg per day Receives: Drug: Voxelotor |
| Period 4 | Experimental | 3000 mg per day Receives: Drug: Voxelotor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-emergent Adverse Events (AEs)
Treatment emergent AEs including SAEs
Measured: approximately 300 days
Secondary outcomes (3)
Number of Participants With Clinically Significant Abnormalities in Hb, Unconjugated Bilirubin, % Reticulocyte, Absolute Reticulocyte, and Lactate Dehydrogenase [LDH]
Measured: approximately 200 days
Number of Participants With an Hb Increase > 1 g/dL Compared to Baseline
Participants with an Hb increase > 1 g/dL compared to Baseline.
Measured: approximately 200 days
Incidence Rate of VOCs
Incidence rate of vaso-occlusive crisis
Measured: approximately 200 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2020
- Study start9 Jan 2020
- Primary completion8 Jun 2021
- Study completion8 Jun 2021
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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 6 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
- NCT04247594
- Sponsor's protocol ID
- GBT440-029
- Other IDs
- C5341042
- Status last verified
- Oct 2023
- First submitted
- 21 Jan 2020
- Last updated
- 21 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- 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 21 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04247594
- Acronym / sponsor ID
- GBT440-029
- Conditions
- Sickle Cell Disease
- Keywords
- Sickle Cell Disease, SCD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Data will not inform further development of Voxelotor
- Enrolment
- 6 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 9 Jan 2020 (actual)
- Primary completion
- 8 Jun 2021 (actual)
- Study completion
- 8 Jun 2021 (actual)
- First posted
- 30 Jan 2020 (actual)
- Results
- Posted 21 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Period 1 | Experimental | Drug: Voxelotor1500 mg per day |
| Period 2 | Experimental | Drug: Voxelotor2000 mg per day |
| Period 3 | Experimental | Drug: Voxelotor2500 mg per day |
| Period 4 | Experimental | Drug: Voxelotor3000 mg per day |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (28 listed)
- 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)
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 |
|---|---|---|
| Voxelotorsynthetic small molecule supplied as 500 mg tablets | Drug | Period 1, Period 2, Period 3, Period 4 |
Primary outcome
Treatment-emergent Adverse Events (AEs)
Time frame: approximately 300 days
Treatment emergent AEs including SAEs
3 secondary outcomes
Number of Participants With Clinically Significant Abnormalities in Hb, Unconjugated Bilirubin, % Reticulocyte, Absolute Reticulocyte, and Lactate Dehydrogenase [LDH]
Time frame: approximately 200 days
Number of Participants With an Hb Increase > 1 g/dL Compared to Baseline
Time frame: approximately 200 days
Incidence Rate of VOCs
Time frame: approximately 200 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2023.
- 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
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Voxelotor in people with Sickle Cell Disease, run by Pfizer at 6 sites in United Kingdom.
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 7 inclusion and 28 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 21 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 21 Nov 2023). 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?
Treatment-emergent Adverse Events (AEs) (time frame: approximately 300 days). 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 21 Nov 2023.