An Extension Study to Further Evaluate the Safety, Tolerability of GBT440 in Patients With Sickle Cell Disease Who Participated in the Study GBT440-001

Study Overview
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Brief Summary
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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
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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).

Official Title
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An Open Label Single Arm Extension Study to Further Evaluate the Safety, Tolerability and Treatment Response of GBT440 in Patients With Sickle Cell Disease Who Participated in the Phase 1 Study GBT440-001

Conditions
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Sickle Cell Disease

Intervention / Treatment
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* Drug: GBT440


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects with SCD aged 18 to 60 years inclusive and >50 kg who have participated in the GBT440-001 study. 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. 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: Subjects requiring chronic transfusion therapy. Subjects receiving a blood transfusion within 30 days of enrollment in this study. Female subjects who are pregnant, trying to become pregnant or lactating. 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). Subjects who have a significant infection or known inflammatory process on admission to this study. Subjects who have acute gastrointestinal symptoms at the time of admission (e.g. nausea, vomiting, diarrhoea, heartburn).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br>Single Arm / open label | Drug: GBT440<br>* Oral drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 2 - 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Assess the Efficacy of GBT440 as Measured by Improvements in Anemia | Data presented are hemoglobin value collected at specific time points. | 2 - 6 months | 
| To Observed Pharmacokinetics in Plasma and Whole Blood. | Measure maximum plasma concentration (Cmax) | 2 - 6 months | 
| To Characterize the Effect of GBT440 on Hemolysis. | Data presented for unconjugated bilirubin at specific time point. | 2 - 6 months |