Sickle Cell Disease
Conditions
Brief summary
Open-label extension study of voxelotor for participants with Sickle Cell Disease who have participated in voxelotor clinical trials.
Detailed description
Open-label extension (OLE) study of voxelotor for participants with Sickle Cell Disease who have participated in voxelotor clinical trials. Up to approximately 600 participants with sickle cell disease (SCD), will be enrolled at approximately 70 clinical sites globally. All participants will receive voxelotor once daily, administered orally as tablets, dispersible tablets, or powder for oral suspension formulation. The objective of this OLE is to assess the safety of, and SCD-related complications of, long-term treatment with voxelotor, in participants who have completed treatment in a Global Blood Therapeutics (GBT)-sponsored voxelotor clinical study.
Interventions
DRUGVoxelotor
All participants will receive voxelotor once daily (QD), administered orally as tablets, dispersible tablets, or a powder for oral suspension formulation (powder formulation packaged as stick packs).
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-Label Extension study available to eligible participants from GBT-sponsored voxelotor clinical studies.
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female participant with SCD, who participated and received study drug in a GBT-sponsored voxelotor clinical study. Note: Participants who discontinued study drug due to an AE, but who remained on study, may be eligible for treatment in this study provided the AE does not pose a risk for treatment with voxelotor. Note: Participants who discontinued Study GBT440-032 as the result of an abnormal transcranial Doppler (TCD) flow velocity assessment (≥ 200 cm/sec) are eligible for treatment in this study. \- Participant has provided written consent/assent (for pediatric participants, both the consent of the participant's legal representative or legal guardian and the participant's assent \[where applicable\] must be obtained).
Exclusion criteria
* Female participant who is breastfeeding or pregnant * Participant withdrew consent from a GBT-sponsored voxelotor clinical study * Known hypersensitivity to voxelotor or any other components of the study drug * Use of St. John's wort, sensitive cytochrome P450 (CYP) 3A4 substrates with a narrow therapeutic index, or moderate or strong CYP3A4 inducers within 30 days of Day 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (AEs) | From date of informed consent until 28 days after last dose of study drug (maximum up to 4.31 years) | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered to be drug related. A treatment emergent AE was defined as an AE with an onset date on or after the date of informed consent until 28 days after discontinuation of drug. AEs included both serious AEs (SAEs) and all non-SAEs. An SAE was an AE or suspected adverse reaction that, at any dose, in the view of the either the investigator or sponsor, resulted in any of the following outcomes: death, was life-threatening, resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. |
| Number of Participants With SAEs | From date of informed consent until 28 days after last dose of study drug (maximum up to 4.31 years) | An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered to be drug related. An SAE was an AE or suspected adverse reaction that, at any dose, in the view of the either the investigator or sponsor, resulted in any of the following outcomes: death, was life-threatening, resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. |
| Number of Participants With Sickle Cell Disease (SCD) Related TEAEs and SAEs | From date of informed consent until 28 days after last dose of study drug (maximum up to 4.31 years) | SCD-related AEs were common complications associated with the study participant's SCD and were not considered to be related to voxelotor unless judged by the investigator to have worsened in severity and/or frequency or changed in nature during the study. SCD-related complications included the following: sickle cell anemia with crisis, acute chest syndrome (ACS), pneumonia, priapism, and osteonecrosis. A treatment emergent AE was defined as an AE with an onset date on or after the date of informed consent until 28 days after discontinuation of drug. An SAE was an AE or suspected adverse reaction that, at any dose, in the view of either the investigator or sponsor, resulted in any of the following outcomes: death, was life-threatening, resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization. |
Countries
Egypt, Lebanon, Nigeria, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 162 participants who had previously completed the following studies: GBT440-032 (NCT04218084) who received placebo, and GBT440-007 (NCT02850406), GBT440-032 (NCT04218084) or GBT440-042 (NCT05561140) who received voxelotor were enrolled in the study GBT440-038 (NCT04188509). All participants enrolled in this study received voxelotor.
Participants by arm
| Arm | Count |
|---|---|
| Voxelotor Participants aged \>= 12 years received voxelotor 1500 mg QD tablets. Participants aged \< 12 years received a voxelotor dose based on their body weight to provide exposure corresponding to the adult dose of 1500 mg QD as powder for oral suspension or dispersible tablet or modified dispersible tablet. Participants received study drug as long they continued to receive clinical benefit that outweighed risk as determined by the investigator and/or until the participant had access to voxelotor from an alternative source. | 162 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Discretion of Investigator | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Noncompliance | 3 |
| Overall Study | Other | 2 |
| Overall Study | Sponsor Decision | 127 |
| Overall Study | Withdrawal of Consent | 1 |
Baseline characteristics
| Characteristic | Voxelotor |
|---|---|
| Age, Continuous | 9.2 Years STANDARD_DEVIATION 5.68 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 161 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Race African | 94 Participants |
| Race/Ethnicity, Customized Race Arab | 2 Participants |
| Race/Ethnicity, Customized Race Black or African American | 40 Participants |
| Race/Ethnicity, Customized Race Middle Eastern or North African | 9 Participants |
| Race/Ethnicity, Customized Race Multi-Racial | 7 Participants |
| Race/Ethnicity, Customized Race White | 10 Participants |
| Sex: Female, Male Female | 75 Participants |
| Sex: Female, Male Male | 87 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 162 |
| other Total, other adverse events | 93 / 162 |
| serious Total, serious adverse events | 53 / 162 |
Outcome results
Primary
Number of Participants With SAEs
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered to be drug related. An SAE was an AE or suspected adverse reaction that, at any dose, in the view of the either the investigator or sponsor, resulted in any of the following outcomes: death, was life-threatening, resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization.
Time frame: From date of informed consent until 28 days after last dose of study drug (maximum up to 4.31 years)
Population: The safety population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Voxelotor | Number of Participants With SAEs | 53 Participants |
Primary
Number of Participants With Sickle Cell Disease (SCD) Related TEAEs and SAEs
SCD-related AEs were common complications associated with the study participant's SCD and were not considered to be related to voxelotor unless judged by the investigator to have worsened in severity and/or frequency or changed in nature during the study. SCD-related complications included the following: sickle cell anemia with crisis, acute chest syndrome (ACS), pneumonia, priapism, and osteonecrosis. A treatment emergent AE was defined as an AE with an onset date on or after the date of informed consent until 28 days after discontinuation of drug. An SAE was an AE or suspected adverse reaction that, at any dose, in the view of either the investigator or sponsor, resulted in any of the following outcomes: death, was life-threatening, resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization.
Time frame: From date of informed consent until 28 days after last dose of study drug (maximum up to 4.31 years)
Population: The safety population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Voxelotor | Number of Participants With Sickle Cell Disease (SCD) Related TEAEs and SAEs | SCD related treatment emergent AE | 60 Participants |
| Voxelotor | Number of Participants With Sickle Cell Disease (SCD) Related TEAEs and SAEs | SCD related SAEs | 43 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (AEs)
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered to be drug related. A treatment emergent AE was defined as an AE with an onset date on or after the date of informed consent until 28 days after discontinuation of drug. AEs included both serious AEs (SAEs) and all non-SAEs. An SAE was an AE or suspected adverse reaction that, at any dose, in the view of the either the investigator or sponsor, resulted in any of the following outcomes: death, was life-threatening, resulted in persistent disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required inpatient hospitalization or prolongation of existing hospitalization.
Time frame: From date of informed consent until 28 days after last dose of study drug (maximum up to 4.31 years)
Population: The safety population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Voxelotor | Number of Participants With Treatment Emergent Adverse Events (AEs) | 105 Participants |