Sickle Cell Disease
Conditions
Brief summary
An Open-label Extension Study of GBT021601 in Participants with Sickle Cell Disease
Detailed description
An Open-label Extension Study to Evaluate the Long-term Safety and Efficacy of GBT021601 Administered to Participants with Sickle Cell Disease Who Have Participated in a GBT021601 Clinical Trial
Interventions
DRUGOsivelotor
Osivelotor
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female aged 6 months or older with SCD who participated and received study drug or placebo in a previous osivelotor clinical study and completed the end of treatment visit. Note: Participants who discontinued study drug in the originating study due to an TEAE, but who remained on study, may be eligible for treatment in this study provided the TEAE does not pose a risk for treatment with osivelotor. 2. Females of childbearing potential are required to have a negative urine pregnancy test prior to dosing on Day 1. Note: Females who become of childbearing potential during the study must be willing to have negative urine pregnancy tests to remain in the study. 3. If sexually active, females of childbearing potential must consistently use highly effective methods of contraception consistently throughout the study and for at least 120 days after the last dose of study drug. If sexually active, male participants must use barrier methods of contraception until 84 days after the last dose of study drug. Male participants are eligible to participate if they agree to the following requirements during the study intervention period and for 84 days after the last dose of study intervention: * Refrain from donating sperm PLUS either * Be abstinent from heterosexual intercourse as their preferred and usual lifestyle OR * Must agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person 4. Participant has provided written informed consent/assent. For underage participants, both the consent of the participant's legal representative or legal guardian and the participant's assent (where applicable) must be obtained based on local requirements.
Exclusion criteria
* Participant withdrew consent or was noncompliant from the originating osivelotor clinical study * Current or recent use of voxelotor. Recent use is defined as within 10 days prior to Day 1 * Current or recent use of crizanlizumab. Recent use is defined as within 90 days prior to Day 1 * Participant has any medical, psychological, safety, or behavioral conditions that, in the opinion of the Investigator, may confound safety interpretation, interfere with compliance, or preclude informed consent * Has received an investigational drug (including investigational vaccines) within 5 times the elimination half-life (if known) or within 30 days (if the elimination half-life- is unknown) prior to study drug administration or is concurrently enrolled in any research judged not to be scientifically or medically compatible with this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | From first dose of study drug up to 56 days after last dose of study drug (approximately up to 736 days) | An adverse event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a clinical investigation. Serious adverse events (SAEs) were defined as any untoward medical occurrence that, at any dose, met one or more of the criteria: death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly or birth defect and other medically significant events. TEAEs are events between first dose of study drug and up to 56 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness of any AE to treatment was based on investigator decision. AEs included both SAEs and all non-serious AEs. |
| Change From Baseline in Hematocrit at Week 12 | Baseline, Week 12 | Change from baseline in hematocrit at week 12 were reported in this outcome measure. |
| Change From Baseline in Hematocrit at Week 48 | Baseline, Week 48 | Change from baseline in hematocrit at week 48 were reported in this outcome measure. |
| Change From Baseline in Leukocytes at Week 12 | Baseline, Week 12 | Change from baseline in leukocytes at week 12 were reported in this outcome measure. |
| Change From Baseline in Leukocytes Week 48 | Baseline, Week 48 | Change from baseline in leukocytes at week 48 were reported in this outcome measure. |
| Change From Baseline in Supine Blood Pressure (SBP) at Week 12 | Baseline, Week 12 | Change from baseline in SBP at week 12 were reported in this outcome measure. |
| Change From Baseline in SBP at Week 48 | Baseline, Week 48 | Change from baseline in SBP at week 48 were reported in this outcome measure. |
| Change From Baseline in Diastolic Blood Pressure (DBP) at Week 12 | Baseline, Week 12 | Change from baseline in DBP at week 12 were reported in this outcome measure. |
| Change From Baseline in DBP at Week 48 | Baseline, Week 48 | Change from baseline in DBP at week 48 were reported in this outcome measure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Rate of Vaso-Occlusive Crisis (VOC) | From the first dose of study drug up to last dose of study drug (approximately up to 680 days) | A VOC was defined as an acute episode of pain that had no medically determined cause other than a vaso-occlusive event, and resulted in a visit to a medical facility (hospitalization, emergency department, urgent care center, outpatient clinic, or infusion center), and required parenteral narcotic agents, parenteral nonsteroidal anti-inflammatory drugs (NSAIDs), or an increase in treatment with oral narcotics. Annualized rate of VOC was reported in this outcome measure. |
| Number of Participants With Sickle Cell Disease (SCD) Related Serious Adverse Events (SAEs) | From first dose of study drug up to 56 days after last dose of study drug (approximately up to 736 days) | SCD is an inherited disorder caused by a point mutation in the beta globin gene which leads to formation of sickle hemoglobin (HbS). SAEs were defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria: death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly or birth defect and other medically significant events. Participants with delayed start are those with a gap in dosing greater than 42 consecutive days from completing the originating study (C5351005 Date of First Dose - C5351004 End of Treatment Date + 1 greater than 42). |
| Change From Baseline in Hemoglobin at Weeks 12, 24, 36, 48, and 60 | Baseline, Weeks 12, 24, 36, 48, and 60 | Change from baseline in hemoglobin at weeks 12, 24, 36, 48 and 60 were reported in this outcome measure. |
| Change From Baseline in Reticulocytes at Weeks 12, 24, 36, 48, and 60 | Baseline, Weeks 12, 24, 36, 48, and 60 | Change from baseline in reticulocytes at weeks 12, 24, 36, 48 and 60 were reported in this outcome measure. |
| Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 12, 24, 36, 48, and 60 | Baseline, Weeks 12, 24, 36, 48, and 60 | Change from baseline in LDH at weeks 12, 24, 36, 48 and 60 were reported in this outcome measure. |
| Change From Baseline in Unconjugated Bilirubin at Weeks 12, 24, 36, 48, and 60 | Baseline, Weeks 12, 24, 36, 48, and 60 | Change from baseline in unconjugated bilirubin at weeks 12, 24, 36, 48 and 60 were reported in this outcome measure. |
Countries
Nigeria, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Participant flow
Pre-assignment details
A total of 47 participants from only Part A of the parent study C5351004 \[NCT05431088\] were enrolled in the current study C5351005 \[NCT05632354\]. Study was terminated based on Sponsor's decision. There were no participants enrolled in 'Participants With Delayed Start: Osivelotor 200 mg' group.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 29.6 Years STANDARD_DEVIATION 12.25 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Race African | 6 Participants |
| Race/Ethnicity, Customized Race Black or African American | 14 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 17 | 0 / 1 | 1 / 5 | 0 / 6 |
| other Total, other adverse events | 14 / 18 | 13 / 17 | 1 / 1 | 5 / 5 | 5 / 6 |
| serious Total, serious adverse events | 5 / 18 | 4 / 17 | 1 / 1 | 2 / 5 | 2 / 6 |
Outcome results
None listed