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

• ClinicalTrials.gov Identifier: NCT03041909
• Recruitment Status: Completed
• First Posted: February 3, 2017
• Results First Posted: January 2, 2019
• Last Update Posted: January 2, 2019
• Sponsor: Global Blood Therapeutics
• Information provided by (Responsible Party): Global Blood Therapeutics

Tracking Information

• First Submitted Date: January 19, 2017
• First Posted Date: February 3, 2017
• Results First Submitted Date: October 2, 2018
• Results First Posted Date: January 2, 2019
• Last Update Posted Date: January 2, 2019
• Study Start Date: August 2016
• Actual Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 18, 2018)

Number of Participants With Treatment-Emergent Adverse Events During Dosing of GBT440 for up to 6 Months. [ Time Frame: 2 - 6 months ]

The safety evaluation will include physical examinations, blood pressure, clinical laboratory tests (hematology, serum biochemistry) and adverse events.

Original Primary Outcome Measures (submitted: February 1, 2017)

To evaluate the safety and tolerability of GBT440 for up to 6 months of dosing. [ Time Frame: 2 - 6 months ]

The safety evaluation will include physical examinations, blood pressure, clinical laboratory tests (hematology, serum biochemistry) and adverse events.

Current Secondary Outcome Measures (submitted: December 18, 2018)

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

Original Secondary Outcome Measures (submitted: February 1, 2017)

• To Assess the Efficacy of GBT440 as Measured by Improvements in Anemia [ Time Frame: 2 - 6 months ]
  Measurement of haemoglobin
• To Observed Pharmacokinetics in Plasma and Whole Blood. [ Time Frame: 2 - 6 months ]
  Measure maximum plasma concentration (Cmax)
• To Characterize the Effect of GBT440 on Hemolysis. [ Time Frame: 2 - 6 months ]
  Measurement of hemolysis include unconjugated bilirubin.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Extension Study to Further Evaluate the Safety, Tolerability of GBT440 in Patients With Sickle Cell Disease Who Participated in the Study GBT440-001
• Official Title: 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
• 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).

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Other
• Condition: Sickle Cell Disease

Intervention

Drug: GBT440

Oral drug

Study Arms

Experimental: Single Arm

Single Arm / open label

Intervention: Drug: GBT440

• Publications *: Howard J, Hemmaway CJ, Telfer P, Layton DM, Porter J, Awogbade M, Mant T, Gretler DD, Dufu K, Hutchaleelaha A, Patel M, Siu V, Dixon S, Landsman N, Tonda M, Lehrer-Graiwer J. A phase 1/2 ascending dose study and open-label extension study of voxelotor in patients with sickle cell disease. Blood. 2019 Apr 25;133(17):1865-1875. doi: 10.1182/blood-2018-08-868893. Epub 2019 Jan 17.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 13, 2018): 5
• Original Estimated Enrollment (submitted: February 1, 2017): 16
• Actual Study Completion Date: August 2017
• Actual Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT03041909
• Other Study ID Numbers: GBT440-024
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol

• Responsible Party: Global Blood Therapeutics
• Study Sponsor: Global Blood Therapeutics
• Collaborators: Not Provided

Investigators

• Study Director: Josh Lehrer-Graiwer, MD; Global Blood Therapeutics, Inc.
• Principal Investigator: Timothy Mant, FRCP, FFPM; Quintiles, Inc.

• PRS Account: Global Blood Therapeutics
• Verification Date: December 2018