A Study of the Safety, Blood Levels and Biological Effects of GBT440 in Healthy Subjects and Subjects With Sickle Cell Disease
A Phase I Randomised, Placebo-controlled, Double-blind, Single and Multiple Ascending Dose Study of the Tolerability and Pharmacokinetics of GBT440 in Healthy Subjects and Patients With Sickle Cell Disease
2 other identifiers
interventional
133
1 country
1
Brief Summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic effects of GBT440 compared with placebo in healthy subjects and subjects with sickle cell disease (SCD).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Dec 2014
Typical duration for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 4, 2014
CompletedFirst Posted
Study publicly available on registry
November 6, 2014
CompletedStudy Start
First participant enrolled
December 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2017
CompletedFebruary 15, 2018
February 1, 2018
2.2 years
November 4, 2014
February 13, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
Safety, as assessed by frequency and severity of adverse events (AEs), and changes in vital signs, 12-lead electrocardiograms (ECGs), and laboratory assessments as compared to baseline
30 - 118 days
Secondary Outcomes (5)
Blood and plasma area under the concentration time curve (AUC) of GBT440
30 - 118 days
Blood and plasma maximum concentration (Cmax) of GBT440
30 - 118 days
Blood and plasma time to maximum concentration (Tmax) of GBT440
30 - 118 days
Percentage of hemoglobin occupied or modified by GBT440
30 days
Change from baseline in heart rate and pulse oximetry following exercise testing in healthy volunteers
30 days
Other Outcomes (5)
Percentage of sickled cells under ex vivo conditions
30 - 90 days
Effect of GBT440 on hemolysis as measured by LDH, direct bilirubin, hemoglobin, and reticulocyte count
30 - 118 days
Change from baseline in pain as measured by visual analog scale
30 days
- +2 more other outcomes
Study Arms (2)
GBT440
EXPERIMENTALSubjects randomized 6:2 to receive daily oral dosing of GBT440 or placebo for 1 day (single dose) and up to 118 days (multiple dose)
Placebo
PLACEBO COMPARATORSubjects randomized 6:2 to receive daily oral dosing of GBT440 or placebo for 1 day (single dose) and up to 118 days (multiple dose)
Interventions
Eligibility Criteria
You may qualify if:
- Healthy male or female of non-child bearing potential; 18 to 55 years old; are non-smokers and have not used nicotine products within 3 months prior to screening.
- Male or female, 18 to 60 years old, with sickle cell disease (hemoglobin SS, HbS/β0thalassemia, HbS/β+thalassemia, or HbSC) not requiring chronic blood transfusion therapy; without hospitalization in 30 days before screening or receiving blood transfusion within 30 days before screening; subjects are allowed concomitant use of hydroxyurea if the dose has been stable for the 3 months prior to screening.
You may not qualify if:
- 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.
- Subjects who consume more than 14 (female subjects) or 21 (male subjects) units of alcohol a week.
- Subjects who have used any investigational product in any clinical trial within 30 days of screening
- Subjects with sickle cell disease who smoke \>10 cigarettes per day; have hemoglobin level \<6 g/dL or \>10.4 g/dL (\> ULN (appropriately corrected for gender) for Cohort 15) at screening; have aspartate aminotransferase (AST) \>4x upper limit of normal or alanine aminotransferase (ALT), or alkaline phosphatase (ALK) \>3x upper limit of normal reference range (ULN) at screening; have moderate or severe renal dysfunction
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Guy's Hospital
London, SE1 9RT, United Kingdom
Related Publications (1)
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.
PMID: 30655275DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Josh Lehrer-Graiwer, MD
Global Blood Therapeutics
- PRINCIPAL INVESTIGATOR
Timothy Mant, FRCP FFPM
Guy's Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 4, 2014
First Posted
November 6, 2014
Study Start
December 1, 2014
Primary Completion
March 1, 2017
Study Completion
May 1, 2017
Last Updated
February 15, 2018
Record last verified: 2018-02