A Study of the Safety, Blood Levels and Biological Effects of GBT440 in Healthy Subjects and Subjects With Sickle Cell Disease

• Sponsor: Global Blood Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02285088
• Collaborator: (none)
• Enrollment: 133
• Location: 1
• Arms: 2
• Actual Duration (Months): 29
• Patients Per Site Per Month: 4.6

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects; Sickle Cell Disease	Drug: GBT440; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 133 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Mar 1, 2017
• Actual Study Completion Date: May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GBT440 Subjects randomized 6:2 to receive daily oral dosing of GBT440 or placebo for 1 day (single dose) and up to 118 days (multiple dose)	Drug: GBT440; GBT440 will be administered as oral capsules
Placebo Comparator: Placebo Subjects randomized 6:2 to receive daily oral dosing of GBT440 or placebo for 1 day (single dose) and up to 118 days (multiple dose)	Drug: Placebo; Matching placebo will be administered as oral capsules

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

1. Blood and plasma area under the concentration time curve (AUC) of GBT440 [30 - 118 days]

2. Blood and plasma maximum concentration (Cmax) of GBT440 [30 - 118 days]

3. Blood and plasma time to maximum concentration (Tmax) of GBT440 [30 - 118 days]

4. Percentage of hemoglobin occupied or modified by GBT440 [30 days]

5. Change from baseline in heart rate and pulse oximetry following exercise testing in healthy volunteers [30 days]

Other Outcome Measures

1. Percentage of sickled cells under ex vivo conditions [30 - 90 days]

2. Effect of GBT440 on hemolysis as measured by LDH, direct bilirubin, hemoglobin, and reticulocyte count [30 - 118 days]

3. Change from baseline in pain as measured by visual analog scale [30 days]

4. Change from baseline in fatigue as measured by questionnaire [30 - 118 days]

5. Exercise capacity as measured by 6-minute walk test [30 - 90 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Guy's Hospital	London		United Kingdom	SE1 9RT

Sponsors and Collaborators

• Global Blood Therapeutics

Investigators

• Study Director: Josh Lehrer-Graiwer, MD, Global Blood Therapeutics
• Principal Investigator: Timothy Mant, FRCP FFPM, Guy's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Global Blood Therapeutics
• ClinicalTrials.gov Identifier: NCT02285088
• Other Study ID Numbers: GBT440-001; 2014-003555-62
• First Posted: Nov 6, 2014
• Last Update Posted: Feb 15, 2018
• Last Verified: Feb 1, 2018

• Additional relevant MeSH terms: Anemia, Sickle Cell

Study Results

No Results Posted as of Feb 15, 2018