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Trial details
Study to Evaluate the Effect of GBT440 in Pediatrics With Sickle Cell Disease
Current status:
Approved
|
Date registered:
12/10/2022
Trial version(s)
History: 19/02/2019
History: 19/02/2019
History: 19/02/2019
Current: 19/02/2019
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Main Information
Primary registry identifying number
LBCTR2019090195
Protocol number
GBT440-007
MOH registration number
1288/ص
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Retrospective
Type of registration: Justify
Requested by Sponsor- Registry not in place upon study initiation
Date of registration in national regulatory agency
11/06/2014
Primary sponsor
Global Blood Therapeutics Inc.
Primary sponsor: Country of origin
United States of America
Public title
Study to Evaluate the Effect of GBT440 in Pediatrics With Sickle Cell Disease
Acronym
Scientific 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
Acronym
Brief summary of the study: English
This study consists of three parts, Parts A, B, C and D. - Part A is a single dose PK study in pediatric participants with Sickle Cell Disease. (Closed on 07 Aug 2017 (LPLV)) - 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 (Closed on 04 Jan 2019 (LPLV)) - 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. - Part D is a multiple dose study that will assess the safety, tolerability, and PK, as well as the hematological effects, of voxelotor in pediatric participants with SCD 6 months to < 4 years of age.
Brief summary of the study: Arabic
دراسة لتقييم تأثير GBT440 عند الأطفال المصابين بمرض الخلايا المنجلية
Health conditions/problem studied: Specify
Sickle Cell Disease
Interventions: Specify
Drug: GBT440 administered as oral capsules, tablets, dispersible tablets or powder for oral suspension.
Key inclusion and exclusion criteria: Inclusion criteria
1. Male or female participants with homozygous hemoglobin SS (HbSS) or hemoglobin S beta0 thalassemia (HbS β0 thal). 2. Age: • Part A – 6 to 17 years of age (Cohort 1 [12 to 17] and Cohort 2 [6 to 11] as defined in the Study Design) • 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 3. Hydroxyurea (HU) therapy: • Parts A, B, and C – A participant taking HU may be enrolled if the dose has been stable for at least 3 months with no anticipated need for dose adjustments 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): • Part A – No restriction • Part B – Hb ≤ 10.5 g/dL • Part C – Hb ≤ 10.5 g/dL • Part D – Hb ≤ 10.5 g/dL 5. Written informed parental/guardian consent and participant assent has been obtained per institutional review board (IRB)/Ethics Committee (EC) policy and requirements, consistent with ICH guidelines. 6. Participants in Part B (only) of the study must complete a minimum of 14 days with ePRO to be enrolled. Investigator discretion will be used to determine if a participant who has previously been screen failed due to a lack of baseline ePRO data collection can be invited back for rescreening. 7. If sexually active and female, must agree to abstain from sexual intercourse or to use a highly effective method of contraception throughout the study period and for 30 days after discontinuation of study drug. If sexually active and male, must agree to abstain from sexual intercourse or willing to use barrier methods of contraception throughout the study period and for 30 days after discontinuation of study drug. 8. Females of child-bearing potential are required to have a negative pregnancy test before the administration of study drug. 9. Sufficient venous access to permit collection of PK samples and monitoring of laboratory safety variables, in the opinion of the Investigator. 10. For Part C only, participants 12 to 17 years of age must have a TCD velocity ≥ 140 cm/sec by nonimaging TCD or ≥ 125 cm/sec by TCDi measured anytime during screening.
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
0
Key inclusion and exclusion criteria: Age maximum
17
Key inclusion and exclusion criteria: Exclusion criteria
1. Any one of the following requiring medical attention within 14 days prior to 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 nonimaging TCD or ≥ 185 cm/sec by TCDi). • For the potential modification, addition of approximately 20 participants enrolled in Part C, TCD ≥ 170 cm/sec by nonimaging TCD or ≥ 155 cm/sec by TCDi. 4. Transfusion within 30 days prior to signing the ICF. 5. Renal dysfunction requiring chronic dialysis or creatinine ≥ 1.5 mg/dL. 6. Hepatic dysfunction characterized by alanine aminotransferase (ALT) > 4× upper limit of normal (ULN) for age. 7. Clinically relevant cardiac abnormality, in the opinion of the Investigator, such as: • Hemodynamically significant heart disease, eg, congenital heart defect, uncompensated heart failure, or any unstable cardiac condition • An arrhythmic heart condition requiring medical therapy 8. QTcF > 450 msec, congenital long QT syndrome, second or third degree heart block at rest (with the exception of asymptomatic Mobitz type I second degree heart block). 9. Received an investigational drug within 30 days or 5 half-lives, whichever is longer, of signing the ICF. 10. Heavy smoker (defined as smoking more than 10 cigarettes/day or its nicotine equivalent including e-cigarettes). 11. Unlikely to comply with the study procedures. 12. Other medical, psychological, or addictive condition that, in the opinion of the Investigator, would confound or interfere with evaluation of safety and/or PK of the investigational drug, prevent compliance with the study protocol, or preclude informed consent. 13. Participants who do not have a TCD window (Part B and C only) (ie, participants who are unable to have a TCD due to skull ossification). 14. For Part C only, prior participation in Part B. 15. Active symptomatic COVID-19 infection. In addition, for Part D only: 16. Body weight < 5 kg for 1 month prior to the screening visit and at the screening visit. 17. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable). 18. History of malignancy within the past 2 years prior to treatment Day 1 requiring chemotherapy and/or radiation (with the exception of local therapy for non-melanoma skin malignancy). 19. Clinically significant bacterial, fungal, parasitic, or viral infection currently receiving or that will require therapy. • Participants with acute bacterial infection requiring antibiotic use should delay screening until the course of antibiotic therapy has been completed and the infection has resolved, in the opinion of the investigator. • Known active hepatitis A, B, or C infection or human immunodeficiency virus (HIV)-positive. • Known active malaria.
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
N/A: Single arm study
Study design: Masking
Open (masking not used)
Study design: Control
Dose comparison
Study phase
2
Study design: Purpose
Treatment
Study design: Assignment
Single
IMP has market authorization
Yes, Worldwide
IMP has market authorization: Specify the countries
USA, UAE, EU, GB, Oman and Kuwait
Name of IMP
OXBRYTA
Year of authorization
2019
Month of authorization
11
Type of IMP
Others
Type of IMP: Specify
Pharmaceutical
Pharmaceutical class
Allosteric modulator of hemoglobin-oxygen affinity
Therapeutic indication
Sickle Cell Disease
Therapeutic benefit
Voxelotor is an orally bioavailable HbS polymerization inhibitor that binds specifically to HbS with a 1:1 stoichiometry, and exhibits preferential partitioning to RBCs. By increasing Hb's affinity for oxygen, voxelotor inhibits HbS polymerization in a dose dependent manner that may improve deformability, decrease the viscosity of SCD blood, and ultimately increase blood flow in the microcirculation, thus improving net O2 delivery. Therefore, chronically modifying 20% to 30% of HbS with voxelotor in subjects with SCD is expected to deliver the clinical benefits of reducing HbS polymerization while improving O2 delivery to peripheral tissues.
Biospecimen retention
None retained
Biospecimen description
N/A
Target sample size
24
Actual enrollment target size
38
Date of first enrollment: Type
Actual
Date of first enrollment: Date
21/07/2016
Date of study closure: Type
Actual
Date of study closure: Date
29/12/2023
Recruitment status
Recruiting
Date of completion
IPD sharing statement plan
No
IPD sharing statement description
N/A
Additional data URL
https://clinicaltrials.gov/ct2/show/NCT02850406
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
Clinicaltrials.gov
NCT02850406
EU Clinical Trials Registry
EudraCT: 2016-004209-15
Sources of Monetary or Material Support
Name
Global Blood Therapeutics, Inc. USA
Secondary Sponsors
Name
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Dr. Adlette
Inati
Tripoli
Lebanon
9613228033
adlette.inati@lau.edu.lb
Nini Hospital
Scientific
Mark
Davis
181 Oyster Point Blvd., South San Francisco, CA 94080
United States of America
(925) 336-1055
mdavis@gbt.com
Global Blood Therapeutics
Public
Dr. Miguel
Abboud
Beirut
Lebanon
9611350000
ma56@aub.edu.lb
American University of Beirut Medical Center
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
American University of Beirut Medical Center
Dr. Miguel Abboud
Pediatric Hematology-Oncology
Approved
Rafik Hariri University Hospital
Dr. Adlette Inati
Pediatric Hematology-Oncology
Approved
Nini Hospital
Dr. Adlette Inati
Pediatric Hematology-Oncology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
American University of Beirut Medical Center
09/07/2018
Dr. Fuad Ziyadeh
irb@aub.edu.lb
9611738025
Rafic Hariri University Hospital
31/08/2018
Dr. Iyad Issa
NA
9611830000
Nini Hospital
31/08/2018
Dr. Nabil Kabbara
NA
9616431400
Countries of Recruitment
Name
Lebanon
United States of America
United Kingdom
Health Conditions or Problems Studied
Condition
Code
Keyword
Sickle Cell Disease
Sickle-cell disorders (D57)
Sickle Cell, Anemia, Hemolytic, Congenital, Hematologic Diseases
Interventions
Intervention
Description
Keyword
Drug
GBT440
Oral Capsule, Tablet, Dispersible Tablet or Powder for Oral Suspension
Primary Outcomes
Name
Time points
Measure
Part A: Pharmacokinetic profile of GBT440 including maximum concentration
Pre-dose to Day 15
Pharmacokinetic profile
Part A: Pharmacokinetic profile of GBT440 including the time taken to reach the maximum concentration
Pre-dose to Day 15
Pharmacokinetic profile
Part A: Pharmacokinetic profile of GBT440 including the total drug concentration over time
Pre-dose to Day 15
Pharmacokinetic profile
Part B: Change in hemoglobin
Baseline to Week 24
Hemoglobin in Blood
Part C: Change in cerebral blood flow
Baseline to Week 48
TAMM TCD velocity
Part D
During Study Duration
Incidence of TEAEs and SAEs
Key Secondary Outcomes
Name
Time points
Measure
Part A: Number of participants with treatment-related adverse events
Days 1 - 15
Assessed by CTCAE v4.03
Part B: Multiple Dose effect on Clinical Measures of Hemolysis
Day 1 - Week 24
Clinical Measures of Hemolysis
Part B: Pharmacokinetic profile of GBT440 including maximum concentration
Pre-dose to Week 24
Pharmacokinetic profile
Part B: Pharmacokinetic profile of GBT440 including the time taken to reach the maximum concentration
Pre-dose to Week 24
Pharmacokinetic profile
Part B: Pharmacokinetic profile of GBT440 including the total drug concentration over time
Pre-dose to Week 24
Pharmacokinetic profile
Part C: Multiple dose effect on clinical measures of hemolysis
Baseline to Week 24 and Week 48
Clinical Measures of Hemolysis
Part C: Change in cerebral blood flow
Baseline to Week 24
Measured by the TAMM TCD velocity
Part C: Pharmacokinetic profile of GBT440 including maximum concentration
Pre-Dose to Week 48
Pharmacokinetic profile
Part C: Pharmacokinetic profile of GBT440 including the time taken to reach the maximum concentration
Pre-Dose to Week 48
Pharmacokinetic profile
Part C: Pharmacokinetic profile of GBT440 including the total drug concentration over time
Pre-Dose to Week 48
Pharmacokinetic profile
Part D: Whole blood and plasma voxelotor PK (Cmax, AUC, t1/2, if appropriate) and occupancy
Baseline to Week 24 and Week 48
Change in Hb, LDH, indirect bilirubin, and reticulocyte count
Part D: Whole blood and plasma voxelotor PK (Cmax, AUC, t1/2, if appropriate) and occupancy
-
Time to initial Hb response, defined as change from baseline in Hb > 1g/dL
Part D: Whole blood and plasma voxelotor PK (Cmax, AUC, t1/2, if appropriate) and occupancy
During whole study duration
Incidence of stroke and VOC
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Update of study info mainly in the following sections: Brief summary english, Inclusion and Exclusion Criteria, Age minimum, IMP market authorization section, Actual enrollment target size, date of study closure anticipated, update of scientific contact person details, Primary and Secondary outcomes (addition of part D)
20/09/2022
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