Sickle Cell Disease
Conditions
Brief summary
This is an open label, single arm study which enrolled 5 subjects with SCD who previously participated in the GBT440-001 study (NCT02285088).
Detailed description
This is an open label, single arm study which enrolled 5 subjects with SCD who previously participated in the GBT440-001 study (NCT02285088). Dosing of study drug was 2 to 6 months, depending on subject's dose assignment in the last administration of study drug in GBT440-001 (NCT02285088). The primary objective of the study was to evaluate the safety and tolerability of up to a total of 6 months dosing of subjects with SCD who participated in the GBT440-001 study (NCT02285088).
Interventions
DRUGGBT440
Oral drug
Sponsors
Global Blood Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects with SCD aged 18 to 60 years inclusive and \>50 kg who have participated in the GBT440-001 study. 2. Subjects, who if female and of child bearing potential, agree to continue to use highly effective methods of contraception prior to enrollment in this study and for 3 months after the last dose of study drug. 3. Subjects, who if male are willing to continue to use barrier methods of contraception, prior to enrollment in this study to 3 months after the last dose of study drug.
Exclusion criteria
1. Subjects requiring chronic transfusion therapy. 2. Subjects receiving a blood transfusion within 30 days of enrollment in this study. 3. Female subjects who are pregnant, trying to become pregnant or lactating. 4. Subjects who have a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, connective tissue diseases or disorders, or additional risk factors for torsades de pointe (e.g., heart failure, hypokalemia, personal or family history of long QTc interval). 5. Subjects who have a significant infection or known inflammatory process on admission to this study. 6. Subjects who have acute gastrointestinal symptoms at the time of admission (e.g. nausea, vomiting, diarrhoea, heartburn).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events During Dosing of GBT440 for up to 6 Months. | 2 - 6 months | The safety evaluation will include physical examinations, blood pressure, clinical laboratory tests (hematology, serum biochemistry) and adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Observed Pharmacokinetics in Plasma and Whole Blood. | 2 - 6 months | Measure maximum plasma concentration (Cmax) |
| To Assess the Efficacy of GBT440 as Measured by Improvements in Anemia | 2 - 6 months | Data presented are hemoglobin value collected at specific time points. |
| To Characterize the Effect of GBT440 on Hemolysis. | 2 - 6 months | Data presented for unconjugated bilirubin at specific time point. |
Countries
United Kingdom
Participant flow
Recruitment details
Subjects enrolled in this study participated in GBT440-001 study (NCT02285088).
Pre-assignment details
There was no screening period as subjects transitioned directly from the GBT440-001 study (NCT02285088).into this study.
Participants by arm
| Arm | Count |
|---|---|
| GBT440 - 2 Months These subjects received GBT440 for 2 months as these subjects received GBT440 for 4 months in GBT440-001 study (NCT02285088) (n=3). | 3 |
| GBT440 - 6 Months The subject received GBT440 for 6 months as this subject received placebo in GBT440-001 study (NCT02285088) (n=1). | 1 |
| GBT440 - 4 Months This subject received GBT440 for 4 months as the subject received GBT440 for 2 months in GBT440-001 study (NCT02285088) (n=1). | 1 |
| Total | 5 |
Baseline characteristics
| Characteristic | GBT440 - 2 Months | GBT440 - 6 Months | GBT440 - 4 Months | Total |
|---|---|---|---|---|
| Age, Continuous | 35 Years | 26 Years | 21 Years | 30 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 0 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 2 / 3 | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 3 | 1 / 1 | 1 / 1 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events During Dosing of GBT440 for up to 6 Months.
The safety evaluation will include physical examinations, blood pressure, clinical laboratory tests (hematology, serum biochemistry) and adverse events.
Time frame: 2 - 6 months
Population: Safety
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GBT440 - 2 Months | Number of Participants With Treatment-Emergent Adverse Events During Dosing of GBT440 for up to 6 Months. | 2 Participants |
| GBT440 - 6 Months | Number of Participants With Treatment-Emergent Adverse Events During Dosing of GBT440 for up to 6 Months. | 1 Participants |
| GBT440 - 4 Months | Number of Participants With Treatment-Emergent Adverse Events During Dosing of GBT440 for up to 6 Months. | 1 Participants |
Secondary
To Assess the Efficacy of GBT440 as Measured by Improvements in Anemia
Data presented are hemoglobin value collected at specific time points.
Time frame: 2 - 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GBT440 - 2 Months | To Assess the Efficacy of GBT440 as Measured by Improvements in Anemia | NA g/dL |
| GBT440 - 6 Months | To Assess the Efficacy of GBT440 as Measured by Improvements in Anemia | NA g/dL |
| GBT440 - 4 Months | To Assess the Efficacy of GBT440 as Measured by Improvements in Anemia | NA g/dL |
Secondary
To Characterize the Effect of GBT440 on Hemolysis.
Data presented for unconjugated bilirubin at specific time point.
Time frame: 2 - 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GBT440 - 2 Months | To Characterize the Effect of GBT440 on Hemolysis. | NA umol/L |
| GBT440 - 6 Months | To Characterize the Effect of GBT440 on Hemolysis. | NA umol/L |
| GBT440 - 4 Months | To Characterize the Effect of GBT440 on Hemolysis. | NA umol/L |
Secondary
To Observed Pharmacokinetics in Plasma and Whole Blood.
Measure maximum plasma concentration (Cmax)
Time frame: 2 - 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GBT440 - 2 Months | To Observed Pharmacokinetics in Plasma and Whole Blood. | NA ug/mL |
| GBT440 - 6 Months | To Observed Pharmacokinetics in Plasma and Whole Blood. | NA ug/mL |
| GBT440 - 4 Months | To Observed Pharmacokinetics in Plasma and Whole Blood. | NA ug/mL |