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Study to Evaluate the Effect of GBT440 in Pediatrics With Sickle Cell Disease (HOPE Kids)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02850406
Recruitment Status : Recruiting
First Posted : August 1, 2016
Last Update Posted : February 18, 2020
Sponsor:
Information provided by (Responsible Party):
Global Blood Therapeutics

Tracking Information
First Submitted Date  ICMJE July 1, 2016
First Posted Date  ICMJE August 1, 2016
Last Update Posted Date February 18, 2020
Actual Study Start Date  ICMJE May 18, 2016
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 14, 2020)
  • Part A: Pharmacokinetic profile of voxelotor including maximum concentration [ Time Frame: Pre-dose to Day 15 ]
  • Part A: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration [ Time Frame: Pre-dose to Day 15 ]
  • Part A: Pharmacokinetic profile of voxelotor including the total drug concentration over time [ Time Frame: Pre-dose to Day 15 ]
  • Part B: Change in hemoglobin [ Time Frame: Baseline to Week 24 ]
  • Part C: Change in cerebral blood flow as measured by the TAMM TCD velocity [ Time Frame: Baseline to Week 48 ]
  • Part D: Treatment-Emergent Adverse Events and Serious Adverse Events [ Time Frame: Baseline to Week 48 ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 27, 2016)
  • Part A: Pharmacokinetic profile of GBT440 including maximum concentration [ Time Frame: Pre-dose to Day 15 ]
  • Part A: Pharmacokinetic profile of GBT440 including the time taken to reach the maximum concentration [ Time Frame: Pre-dose to Day 15 ]
  • Part A: Pharmacokinetic profile of GBT440 including the total drug concentration over time [ Time Frame: Pre-dose to Day 15 ]
  • Part B: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: Days 1 - 58 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 14, 2020)
  • Part A: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: Days 1 - 15 ]
  • Part B: Multiple Dose effect on Clinical Measures of Hemolysis [ Time Frame: Day 1 - Week 24 ]
  • Part B: Pharmacokinetic profile of voxelotor including maximum concentration [ Time Frame: Pre-dose to Week 24 ]
  • Part B: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration [ Time Frame: Pre-dose to Week 24 ]
  • Part B: Pharmacokinetic profile of voxelotor including the total drug concentration over time [ Time Frame: Pre-dose to Week 24 ]
  • Part C: Multiple dose effect on clinical measures of hemolysis [ Time Frame: Baseline to Week 24 and Week 48 ]
  • Part C: Change in cerebral blood flow [ Time Frame: Baseline to Week 24 ]
  • Part C: Pharmacokinetic profile of voxelotor including maximum concentration [ Time Frame: Pre-Dose to Week 48 ]
  • Part C: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration [ Time Frame: Pre-Dose to Week 48 ]
  • Part C: Pharmacokinetic profile of voxelotor including the total drug concentration over time [ Time Frame: Pre-Dose to Week 48 ]
  • Part D: Pharmacokinetic profile of voxelotor including percent Hemoglobin occupancy [ Time Frame: Baseline to Week 48 ]
  • Part D: Change in Hemoglobin [ Time Frame: Baseline to Week 24 ]
  • Part D: Change in Lactate Dehydrogenase [ Time Frame: Baseline to Week 24 ]
  • Part D: Change in Indirect Bilirubin [ Time Frame: Baseline to Week 24 ]
  • Part D: Change in Reticulocyte Count [ Time Frame: Baseline to Week 24 ]
  • Part D: Time to initial Hemoglobin response [ Time Frame: Baseline to Week 48 ]
    Change in baseline in Hb > 1g/dL
Original Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2016)
  • Part A: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: Days 1 - 15 ]
  • Part B Multiple Dose effect on Laboratory Biomarkers of Hemolysis [ Time Frame: Days 1 - 58 ]
    To evaluate the effect of GBT440 on clinical laboratory biomarkers of hemolysis
  • Part B: Pharmacokinetic profile of GBT440 including maximum concentration [ Time Frame: Pre-dose to Day 58 ]
  • Part B: Pharmacokinetic profile of GBT440 including the time taken to reach the maximum concentration [ Time Frame: Pre-dose to Day 58 ]
  • Part B: Pharmacokinetic profile of GBT440 including the total drug concentration over time [ Time Frame: Pre-dose to Day 58 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Effect of GBT440 in Pediatrics With Sickle Cell Disease
Official Title  ICMJE 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
Brief Summary This study consists of four parts, Parts A, B, C, and D. Part A is a single dose pharmacokinetic (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 voxelotor in pediatric participants with Sickle Cell Disease who are 4 to 17 years of age. Part D is a multiple dose, safety, tolerability, and PK study, which will examine the hematological effects of voxelotor in pediatric participants with Sickle Cell Disease who are between 9 months to < 4 years of age.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Sickle Cell Disease
Intervention  ICMJE Drug: Voxelotor
Part A: Voxelotor will be administered as oral capsules or tablets Part B: Voxelotor will be administered as oral capsules or tablets Part C: Voxelotor will be administered as oral dispersible tablets or powder for oral suspension Part D: Voxelotor will be administered as powder for oral suspension
Study Arms  ICMJE Experimental: Voxelotor

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

  • Part A: Subjects to receive daily oral dosing of voxelotor for 1 day (single dose)
  • Part B: Subjects to receive daily oral dosing of voxelotor for up to 24 weeks (multiple dose)
  • Part C: Subjects to receive daily oral dosing of voxelotor for up to 48 weeks (1500mg or 1500mg equivalent dose)
  • Part D: Subjects to receive daily oral dosing of voxelotor for up to 48 weeks (1500mg or 1500mg equivalent dose)
Intervention: Drug: Voxelotor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 14, 2020)
155
Original Estimated Enrollment  ICMJE
 (submitted: July 27, 2016)
30
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female participants with homozygous hemoglobin SS (HbSS) or hemoglobin S beta0 thalassemia (HbS β0thal)
  2. Age:

    1. Part A - 6 to 17 years of age
    2. Part B - 12 to 17 years of age
    3. Part C - 4 to 17 years of age
    4. Part D - 9 months to <4 years of age
  3. Hydroxyurea (HU) therapy:

    • Parts A, B, and C: 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.
    • Part D: A participant taking HU may be enrolled if the dose has been stable for at least 1 month. Titration to the maximum tolerated dose (MTD) is allowed during the study.
  4. Hemoglobin (HB):

    1. Part A - No restriction
    2. Parts B, C, & D - Hb ≤ 10.5 g/dL

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 by non-imaging TCD or ≥185 cm/sec by TCDi).
  4. Transfusion within 30 days prior to signing the ICF

Exclusion Criteria for Part D Only:

16. Body weight <5 kg for 1 month prior to the screening visit and at the screening visit.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 9 Months to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Margaret Tonda, PharmD (650) 741-7761 mtonda@gbt.com
Contact: Aimee Enriquez (650) 741-7777 aenriquez@gbt.com
Listed Location Countries  ICMJE Lebanon,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02850406
Other Study ID Numbers  ICMJE GBT440-007
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Global Blood Therapeutics
Study Sponsor  ICMJE Global Blood Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Margaret Tonda, PharmD Global Blood Therapeutics, Inc.
PRS Account Global Blood Therapeutics
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP