Study to Evaluate the Effect of GBT440 in Pediatrics With Sickle Cell Disease (HOPE Kids)
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| ClinicalTrials.gov Identifier: NCT02850406 |
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Recruitment Status :
Recruiting
First Posted : August 1, 2016
Last Update Posted : May 19, 2023
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Sponsor:
Global Blood Therapeutics
Collaborator:
Pfizer
Information provided by (Responsible Party):
Global Blood Therapeutics
- Study Details
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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 |
|---|---|---|
| Sickle Cell Disease | Drug: Voxelotor | Phase 2 |
Expanded Access : An investigational treatment associated with this study is temporarily not available outside the clinical trial. More info ...
| Study Type : | Interventional (Clinical Trial) |
| Estimated 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 : | July 21, 2016 |
| Estimated Primary Completion Date : | December 2023 |
| Estimated Study Completion Date : | December 2023 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Sickle cell disease
Drug Information available for:
Voxelotor
| Arm | Intervention/treatment |
|---|---|
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Experimental: Voxelotor
Subjects to receive daily oral dosing of voxelotor according to which Part (A, B, C, or D), the subject is participating in:
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Drug: Voxelotor
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Primary Outcome Measures :
- Part A: Pharmacokinetic profile of voxelotor including maximum concentration [ Time Frame: Pre-dose to Day 15 ]Maximum observed concentration (Cmax), area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last), and area under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of voxelotor in whole blood
- Part A: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration [ Time Frame: Pre-dose to Day 15 ]Maximum observed concentration (Cmax), area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last), and area under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of voxelotor in whole blood
- Part A: Pharmacokinetic profile of voxelotor including the total drug concentration over time [ Time Frame: Pre-dose to Day 15 ]Maximum observed concentration (Cmax), area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC0-last), and area under the concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of voxelotor in whole blood
- Part B: Change in hemoglobin [ Time Frame: Baseline to Week 24 ]Change from baseline to Week 24 in Hb
- Part C: Change in cerebral blood flow as measured by the TAMM TCD velocity [ Time Frame: Baseline to Week 48 ]Change from baseline to 12 and 24 weeks in cerebral blood flow as measured by the time-averaged mean of the maximum (TAMM) TCD velocity
- Part D: Treatment-Emergent Adverse Events and Serious Adverse Events [ Time Frame: Baseline to Week 48 ]Participants will be monitored throughout the study for AEs, from the time informed consent is obtained through the EOS visit. The Investigator will assess each AE for seriousness, intensity and relationship to investigational product.
Secondary Outcome Measures :
- 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 as measured by TAMM TCD velocity [ Time Frame: Baseline to Week 24 ]
- Part C: Time to initial Hemoglobin response [ Time Frame: Baseline to Week 48 ]Change from baseline in Hb > 1g/dL
- Part C: Pharmacokinetic profile of voxelotor including percent Hemoglobin occupancy [ Time Frame: Baseline to Week 48 ]
- Part C: Proportion of participants with normal TCD flow velocity [ Time Frame: Baseline to Week 48 ]
- Part C: Incidence of stroke and VOC [ Time Frame: Baseline 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 and Week 48 ]
- Part D: Change in Lactate Dehydrogenase [ Time Frame: Baseline to Week 24 and Week 48 ]
- Part D: Change in Indirect Bilirubin [ Time Frame: Baseline to Week 24 and Week 48 ]
- Part D: Change in Reticulocyte Count [ Time Frame: Baseline to Week 24 and Week 48 ]
- Part D: Time to initial Hemoglobin response [ Time Frame: Baseline to Week 48 ]Change from baseline in Hb > 1g/dL
- Part D: Incidence of stroke and VOC [ Time Frame: Baseline to Week 48 ]
Information from the National Library of Medicine
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| Ages Eligible for Study: | 6 Months to 17 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Male or female participants with homozygous hemoglobin SS (HbSS) or hemoglobin S beta0 thalassemia (HbS β0thal)
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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
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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.
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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:
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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.
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: Mark Davis, MS | (925)336-1055 | Mark.Davis@Pfizer.com | |
| Contact: Aimee Enriquez | (650)741-7777 | Aimee.Enriquez@Pfizer.com |
Locations
Show 18 study locations
Sponsors and Collaborators
Global Blood Therapeutics
Pfizer
Investigators
| Study Director: | Mark Davis, MS | Global Blood Therapeutics |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Global Blood Therapeutics |
| ClinicalTrials.gov Identifier: | NCT02850406 |
| Other Study ID Numbers: |
GBT440-007 C5341020 ( Other Identifier: Pfizer ) |
| First Posted: | August 1, 2016 Key Record Dates |
| Last Update Posted: | May 19, 2023 |
| Last Verified: | May 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| 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:
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Anemia, Sickle Cell Anemia, Hemolytic, Congenital Anemia, Hemolytic Anemia |
Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn |