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Study to Evaluate the Effect of GBT440 in Pediatrics With Sickle Cell Disease

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ClinicalTrials.gov Identifier: NCT02850406
Recruitment Status : Recruiting
First Posted : August 1, 2016
Last Update Posted : November 1, 2018
Sponsor:
Information provided by (Responsible Party):
Global Blood Therapeutics

Brief Summary:
This study consists of three parts, Parts A, B, and C. Part A is a single dose PK study in pediatric participants with Sickle Cell Disease. Part B is a multiple dose, safety, exploratory, efficacy, and PK study in adolescent Sickle Cell Disease participants who were 12-17 years of age. Part C is a multiple dose, safety, tolerability, and PK study, which includes the assessment of hematological effects and the effect on TCD flow velocity of GBT440 is pediatric participants with Sickle Cell Disease who are 4 to 17 years of age.

Condition or disease Intervention/treatment Phase
Sickle Cell Disease Drug: GBT440 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 125 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2a, Open-label, Single and Multiple Dose Study to Evaluate the Pharmacokinetics, Safety, Tolerability, and Exploratory Treatment Effect of GBT440 in Pediatric Participants With Sickle Cell Disease
Study Start Date : May 2016
Estimated Primary Completion Date : May 2022
Estimated Study Completion Date : May 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GBT440

Subjects to receive daily oral dosing of GBT440 according to which Part (A, B, or C), the subject is participating in:

  • Part A: Subjects to receive daily oral dosing of GBT440 for 1 day (single dose)
  • Part B: Subjects to receive daily oral dosing of GBT440 for up to 24 weeks (multiple dose)
  • Part C: Subjects to receive daily oral dosing of GBT440 for up to 48 weeks (1500mg or 1500mg equivalent dose)
Drug: GBT440
GBT440 will be administered as oral capsules




Primary Outcome Measures :
  1. Part A: Pharmacokinetic profile of GBT440 including maximum concentration [ Time Frame: Pre-dose to Day 15 ]
  2. Part A: Pharmacokinetic profile of GBT440 including the time taken to reach the maximum concentration [ Time Frame: Pre-dose to Day 15 ]
  3. Part A: Pharmacokinetic profile of GBT440 including the total drug concentration over time [ Time Frame: Pre-dose to Day 15 ]
  4. Part B: Change in hemoglobin [ Time Frame: Baseline to Week 24 ]
  5. Part C: Change in cerebral blood flow as measured by the TAMM TCD velocity [ Time Frame: Baseline to Week 48 ]

Secondary Outcome Measures :
  1. Part A: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: Days 1 - 15 ]
  2. Part B Multiple Dose effect on Clinical Measures of Hemolysis [ Time Frame: Day 1 - Week 24 ]
    To evaluate the effect of GBT440 on clinical measures of hemolysis

  3. Part B: Pharmacokinetic profile of GBT440 including maximum concentration [ Time Frame: Pre-dose to Week 24 ]
  4. Part B: Pharmacokinetic profile of GBT440 including the time taken to reach the maximum concentration [ Time Frame: Pre-dose to Week 24 ]
  5. Part B: Pharmacokinetic profile of GBT440 including the total drug concentration over time [ Time Frame: Pre-dose to Week 24 ]
  6. Part C: Multiple dose effect on clinical measures of hemolysis [ Time Frame: Baseline to Week 24 and Week 48 ]
  7. Part C: Change in cerebral blood flow [ Time Frame: Baseline to Week 24 ]
  8. Part C: Pharmacokinetic profile of GBT440 including maximum concentration [ Time Frame: Pre-Dose to Week 48 ]
  9. Part C: Pharmacokinetic profile of GBT440 including the time taken to reach the maximum concentration [ Time Frame: Pre-Dose to Week 48 ]
  10. Part C: Pharmacokinetic profile of GBT440 including the total drug concentration over time [ Time Frame: Pre-Dose to Week 48 ]


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Ages Eligible for Study:   4 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female participants with homozygous hemoglobin SS (HbSS) or hemoglobin S beta0 thalassemia (HbS β0thal)
  2. A participant taking hydroxyurea (HU) may be enrolled if the dose has been stable for at least 3 months with no anticipated need for dose adjustment during the study and no sign of hematological toxicity.
  3. Hemoglobin (HB):

    1. Part A - No restriction
    2. Part B - Hb ≤ 10.5 g/dL
    3. Part C - Hb ≤ 10.5 g/dL
  4. Written informed parental/guardian consent and participant assent has been obtained per institutional review board (IRB)/Ethics Committee (EC) policy and requirements, consistent with International Council on Harmonisation (ICH) guidelines.

10. For Part C only: Participants 12 to 17 years of age must have a TCD velocity of ≥ 140 cm/sec measured anytime during screening.

Exclusion Criteria:

  1. Any one of the following requiring medical attention within 14 days of signing the Informed Consent Form (ICF):

    • Vaso-occlusive crisis (VOC)
    • Acute chest syndrome (ACS)
    • Splenic sequestration crisis
    • Dactylitis
  2. Requires chronic transfusion therapy
  3. History of stroke or meeting criteria for primary stroke prophylaxis (history of two TCD measurements ≥ 200 cm/sec)
  4. Transfusion within 30 days prior to signing the ICF

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02850406


Contacts
Contact: Josh Lehrer-Graiwer, MD (650) 741-7744 jlehrer@gbt.com

Locations
United States, California
Active, not recruiting
Oakland, California, United States, 94609
United States, Georgia
Recruiting
Atlanta, Georgia, United States, 30342
Contact: Morgan Barnett    732-135-5976    Morgan.Barnett@choa.org   
United States, Illinois
Active, not recruiting
Chicago, Illinois, United States, 60611
Withdrawn
Chicago, Illinois, United States, 60612
United States, Missouri
Active, not recruiting
Kansas City, Missouri, United States, 64108
United States, New Jersey
Active, not recruiting
New Brunswick, New Jersey, United States, 08901
United States, Ohio
Active, not recruiting
Cleveland, Ohio, United States, 38105
United States, Pennsylvania
Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Angela Martino    412-692-6467    Angela.Martino2@chp.edu   
United States, Tennessee
Active, not recruiting
Memphis, Tennessee, United States, 38105
Lebanon
Active, not recruiting
Beirut, Hamrah, Lebanon, 1107-2020
Sponsors and Collaborators
Global Blood Therapeutics
Investigators
Study Director: Josh Lehrer-Graiwer, MD Global Blood Therapeutics

Responsible Party: Global Blood Therapeutics
ClinicalTrials.gov Identifier: NCT02850406     History of Changes
Other Study ID Numbers: GBT440-007
First Posted: August 1, 2016    Key Record Dates
Last Update Posted: November 1, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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