Clincosm LogoSign in Get a demo

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

Sponsor
Global Blood Therapeutics (Industry)
Overall Status
Recruiting
CT.gov ID
NCT02850406
Collaborator
(none)
155
Enrollment
18
Locations
1
Arm
78.5
Anticipated Duration (Months)
8.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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 ages 6 to 17 years.

  • Part B is a multiple dose, safety, exploratory, efficacy, and PK study in adolescent participants with Sickle Cell Disease ages 12 to 17 years.

  • 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 ages 4 to 17 years.

  • Part D is a multiple dose, safety, tolerability, and PK study, which examines the hematological effects of voxelotor in pediatric participants with Sickle Cell Disease ages 6 months to < 4 years.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
155 participants
Allocation:
N/A
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 Treatment Effect of GBT440 in Pediatric Participants With Sickle Cell Disease
Actual Study Start Date :
May 18, 2016
Anticipated Primary Completion Date :
Dec 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

Arm Intervention/Treatment
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 equivalent dose)

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

Outcome Measures

Primary Outcome Measures

  1. Part A: Pharmacokinetic profile of voxelotor including maximum concentration [Pre-dose to Day 15]

  2. Part A: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration [Pre-dose to Day 15]

  3. Part A: Pharmacokinetic profile of voxelotor including the total drug concentration over time [Pre-dose to Day 15]

  4. Part B: Change in hemoglobin [Baseline to Week 24]

  5. Part C: Change in cerebral blood flow as measured by the TAMM TCD velocity [Baseline to Week 48]

  6. Part D: Treatment-Emergent Adverse Events and Serious Adverse Events [Baseline to Week 48]

Secondary Outcome Measures

  1. Part A: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [Days 1 - 15]

  2. Part B: Multiple Dose effect on Clinical Measures of Hemolysis [Day 1 - Week 24]

  3. Part B: Pharmacokinetic profile of voxelotor including maximum concentration [Pre-dose to Week 24]

  4. Part B: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration [Pre-dose to Week 24]

  5. Part B: Pharmacokinetic profile of voxelotor including the total drug concentration over time [Pre-dose to Week 24]

  6. Part C: Multiple dose effect on clinical measures of hemolysis [Baseline to Week 24 and Week 48]

  7. Part C: Change in cerebral blood flow as measured by TAMM TCD velocity [Baseline to Week 24]

  8. Part C: Time to initial Hemoglobin response [Baseline to Week 48]

    Change from baseline in Hb > 1g/dL

  9. Part C: Pharmacokinetic profile of voxelotor including percent Hemoglobin occupancy [Baseline to Week 48]

  10. Part C: Proportion of participants with normal TCD flow velocity [Baseline to Week 48]

  11. Part C: Incidence of stroke and VOC [Baseline to Week 48]

  12. Part D: Pharmacokinetic profile of voxelotor including percent Hemoglobin occupancy [Baseline to Week 48]

  13. Part D: Change in Hemoglobin [Baseline to Week 24 and Week 48]

  14. Part D: Change in Lactate Dehydrogenase [Baseline to Week 24 and Week 48]

  15. Part D: Change in Indirect Bilirubin [Baseline to Week 24 and Week 48]

  16. Part D: Change in Reticulocyte Count [Baseline to Week 24 and Week 48]

  17. Part D: Time to initial Hemoglobin response [Baseline to Week 48]

    Change from baseline in Hb > 1g/dL

  18. Part D: Incidence of stroke and VOC [Baseline to Week 48]

Eligibility Criteria

Criteria

Ages Eligible for Study:
6 Months to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Male or female participants with homozygous hemoglobin SS (HbSS) or hemoglobin S beta0 thalassemia (HbS β0thal)

  • Age:

  • Part A - 6 to 17 years of age

  • Part B - 12 to 17 years of age

  • Part C - 4 to 17 years of age

  • Part D - 6 months to <4 years of age

  • 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.

  • Hemoglobin (HB):

  • Part A - No restriction

  • Parts B, C, & D - Hb ≤ 10.5 g/dL

  • 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:
  • 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

  • Requires chronic transfusion therapy

  • 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).

  • Transfusion within 30 days prior to signing the ICF

Exclusion Criteria for Part D Only:
  • Body weight <5 kg for 1 month prior to the screening visit and at the screening visit.

Contacts and Locations

Locations

Site City State Country Postal Code
1 UCSF Benioff Children's Hospital Oakland Oakland California United States 94609
2 Children's National Medical Center Washington District of Columbia United States 20010
3 Children's Healthcare of Atlanta Atlanta Georgia United States 30342
4 Ann & Robert Lurie Children's Hospital of Chicago Chicago Illinois United States 60611
5 Our Lady of the Lake Regional Medical Center Baton Rouge Louisiana United States 70808
6 Children's Mercy Hospital Kansas City Kansas City Missouri United States 64108
7 Rutgers - Cancer Institute of New Jersey New Brunswick New Jersey United States 08901
8 East Carolina University Brody School of Medicine Greenville North Carolina United States 27834
9 The Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
10 Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania United States 15224
11 St. Jude Children's Research Hospital Memphis Tennessee United States 38105
12 American University of Beirut Medical Center AUBMC Beirut Hamrah Lebanon 1107-2020
13 Rafik Hariri University Hospital (RHUH) Beirut Lebanon 28337401
14 Nini Hospital Tripoli Lebanon 1300
15 University College London Hospitals NHS Foundation Trust London United Kingdom NW1 2PG
16 Evelina London Children's Hospital - Guy's and St. Thomas' NHS Foundation Trust London United Kingdom SE1 9RT
17 Royal London Hospital, Barts Health NHS Trust London United Kingdom SE1 9RT
18 Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust Manchester United Kingdom M13 9WL

Sponsors and Collaborators

  • Global Blood Therapeutics

Investigators

  • Study Director: Mark Davis, MS, Global Blood Therapeutics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Global Blood Therapeutics
ClinicalTrials.gov Identifier:
NCT02850406
Other Study ID Numbers:
  • GBT440-007
First Posted:
Aug 1, 2016
Last Update Posted:
Jul 12, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Anemia, Sickle Cell

Study Results

No Results Posted as of Jul 12, 2022