Clinical trial NCT02850406: Study to Evaluate the Effect of GBT440 in Pediatrics With Sickle Cell Disease
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Sickle Cell Disease
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2016-08-01
Enrollment: 147
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part A: Pharmacokinetic profile of voxelotor including maximum concentration
timeFrame: Pre-dose to Day 15
measure: Part A: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration
timeFrame: Pre-dose to Day 15
measure: Part A: Pharmacokinetic profile of voxelotor including the total drug concentration over time
timeFrame: Pre-dose to Day 15
measure: Part B: Change in hemoglobin
timeFrame: Baseline to Week 24
measure: Part C: Change in cerebral blood flow as measured by the TAMM TCD velocity
timeFrame: Baseline to Week 48
measure: Part D: Treatment-Emergent Adverse Events and Serious Adverse Events
timeFrame: Baseline to Week 48
Secondary outcomes:
measure: Part A: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
timeFrame: Days 1 - 15
measure: Part B: Multiple Dose effect on Clinical Measures of Hemolysis
timeFrame: Day 1 - Week 24
measure: Part B: Pharmacokinetic profile of voxelotor including maximum concentration
timeFrame: Pre-dose to Week 24
measure: Part B: Pharmacokinetic profile of voxelotor including the time taken to reach the maximum concentration
timeFrame: Pre-dose to Week 24
measure: Part B: Pharmacokinetic profile of voxelotor including the total drug concentration over time
timeFrame: Pre-dose to Week 24
measure: Part C: Multiple dose effect on clinical measures of hemolysis
timeFrame: Baseline to Week 24 and Week 48
measure: Part C: Change in cerebral blood flow as measured by TAMM TCD velocity
timeFrame: Baseline to Week 24
measure: Part C: Time to initial Hemoglobin response
timeFrame: Baseline to Week 48
measure: Part C: Pharmacokinetic profile of voxelotor including percent Hemoglobin occupancy
timeFrame: Baseline to Week 48
measure: Part C: Proportion of participants with normal TCD flow velocity
timeFrame: Baseline to Week 48
measure: Part C: Incidence of stroke and VOC
timeFrame: Baseline to Week 48
measure: Part D: Pharmacokinetic profile of voxelotor including percent Hemoglobin occupancy
timeFrame: Baseline to Week 48
measure: Part D: Change in Hemoglobin
timeFrame: Baseline to Week 24 and Week 48
measure: Part D: Change in Lactate Dehydrogenase
timeFrame: Baseline to Week 24 and Week 48
measure: Part D: Change in Indirect Bilirubin
timeFrame: Baseline to Week 24 and Week 48
measure: Part D: Change in Reticulocyte Count
timeFrame: Baseline to Week 24 and Week 48
measure: Part D: Time to initial Hemoglobin response
timeFrame: Baseline to Week 48
measure: Part D: Incidence of stroke and VOC
timeFrame: Baseline to Week 48
Other outcomes:
Locations:
city: Brentwood
country: United States
facility: Brentwood Clinic UCSF Benioff Children's Hospital Oakland
state: California
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Walnut Creek
country: United States
facility: UCSF Benioff Children's Hospital Walnut Creek
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Atlanta
country: United States
facility: Emory Children's Center
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta Scottish Rite
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Illinois at Chicago Clinical Research Center
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Hospital and Health Sciences System
state: Illinois
city: Baton Rouge
country: United States
facility: Our Lady of the Lake Children's Hospital (IP Address)
state: Louisiana
city: Baton Rouge
country: United States
facility: St. Jude Affiliate Clinic at Our Lady of the Lake Children's Health
state: Louisiana
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers-Robert Wood Johnson Medical School
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers-Robert Wood Johnson Medical School
state: New Jersey
city: Greenville
country: United States
facility: Brody School of Medicine at East Carolina University
state: North Carolina
city: Greenville
country: United States
facility: ECU Physicians
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Rainbow Babies & Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital - Pharmaceutical Services
state: Tennessee
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Beirut
country: Lebanon
facility: American University of Beirut - Medical Center
city: Beirut
country: Lebanon
facility: Rafik Hariri University Hospital
city: Tripoli
country: Lebanon
facility: Nini Hospital
city: London
country: United Kingdom
facility: University College London Hospital, NHS Foundation Trust
state: Greater London
city: London
country: United Kingdom
facility: Barts Health NHS Trust, The Royal London Hospital
city: London
country: United Kingdom
facility: Guy's and St Thoma's NHS Foundation Trust, Evelina London Children's Hospital
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust, Royal Manchester Children's Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Estepp JH, Kalpatthi R, Woods G, Trompeter S, Liem RI, Sims K, Inati A, Inusa BPD, Campbell A, Piccone C, Abboud MR, Smith-Whitley K, Dixon S, Tonda M, Washington C, Griffin NM, Brown C. Safety and efficacy of voxelotor in pediatric patients with sickle cell disease aged 4 to 11 years. Pediatr Blood Cancer. 2022 Aug;69(8):e29716. doi: 10.1002/pbc.29716. Epub 2022 Apr 21.