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

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

This is an open label, single arm study which enrolled 5 subjects with SCD who previously participated in the GBT440-001 study (NCT02285088).

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: GBT440

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
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 9RT
    • The BRC Research Facility, Floor 15 The Tower Wing

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm; Single Arm / open label	Drug: GBT440; Oral drug

What is the study measuring?

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

Collaborators and Investigators

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

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: January 19, 2017
• First Submitted That Met QC Criteria: February 1, 2017
• First Posted (Estimate): February 3, 2017

Study Record Updates

• Last Update Posted (Actual): January 2, 2019
• Last Update Submitted That Met QC Criteria: December 18, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: GBT440-024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Supporting Information Type: Study Protocol