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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Global Blood Therapeutics
ClinicalTrials.gov Identifier:
NCT02285088
First received: November 4, 2014
Last updated: March 13, 2017
Last verified: March 2017
  Purpose
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 Intervention Phase
Healthy Subjects Sickle Cell Disease Drug: GBT440 Drug: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Global Blood Therapeutics:

Primary Outcome Measures:
  • 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 [ Time Frame: 30 - 118 days ]

Secondary Outcome Measures:
  • Blood and plasma area under the concentration time curve (AUC) of GBT440 [ Time Frame: 30 - 118 days ]
  • Blood and plasma maximum concentration (Cmax) of GBT440 [ Time Frame: 30 - 118 days ]
  • Blood and plasma time to maximum concentration (Tmax) of GBT440 [ Time Frame: 30 - 118 days ]
  • Percentage of hemoglobin occupied or modified by GBT440 [ Time Frame: 30 days ]
  • Change from baseline in heart rate and pulse oximetry following exercise testing in healthy volunteers [ Time Frame: 30 days ]

Other Outcome Measures:
  • Percentage of sickled cells under ex vivo conditions [ Time Frame: 30 - 90 days ]
  • Effect of GBT440 on hemolysis as measured by LDH, direct bilirubin, hemoglobin, and reticulocyte count [ Time Frame: 30 - 118 days ]
  • Change from baseline in pain as measured by visual analog scale [ Time Frame: 30 days ]
  • Change from baseline in fatigue as measured by questionnaire [ Time Frame: 30 - 118 days ]
  • Exercise capacity as measured by 6-minute walk test [ Time Frame: 30 - 90 days ]

Estimated Enrollment: 128
Actual Study Start Date: December 2014
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02285088

Locations
United Kingdom
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
  More Information

Responsible Party: Global Blood Therapeutics
ClinicalTrials.gov Identifier: NCT02285088     History of Changes
Other Study ID Numbers: GBT440-001
2014-003555-62 ( EudraCT Number )
Study First Received: November 4, 2014
Last Updated: March 13, 2017

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on June 27, 2017