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Trial details
Trial details
Evaluate the Pharmacokinetics and Safety of Etavopivat in Pediatric Patients with Sickle Cell Disease
Current status:
Approved
|
Date registered:
23/08/2023
Trial version(s)
History: 08/09/2022
Current: 08/09/2022
Click here to view the tips and fields' descriptions
Main Information
Primary registry identifying number
LBCTR2022095118
Protocol number
4202-HEM-202
MOH registration number
Trial already registered with the MoPH
Study registered at the country of origin
Poor pool of patients with Sickle Cell Disease
Type of registration
Prospective
Date of registration in national regulatory agency
26/09/2022
Primary sponsor
Forma Therapeutics, Inc.
Primary sponsor: Country of origin
United States of America
Public title
Evaluate the Pharmacokinetics and Safety of Etavopivat in Pediatric Patients with Sickle Cell Disease
Acronym
Scientific title
A Single Arm, Open Label, Phase 1/2 Study to Evaluate the Pharmacokinetics and Safety of Etavopivat in Pediatric Patients with Sickle Cell Disease
Acronym
Brief summary of the study: English
This clinical trial is a Phase 1/2 study that will evaluate the Pharmacokinetics and Safety of Etavopivat (FT-4202) in Pediatric Patients from 12 to 18 years with Sickle Cell Disease to improve the amount of hemoglobin in the blood and to reduce the number of vaso-occlusive crises (times when the blood vessels become blocked and cause pain).
Brief summary of the study: Arabic
هذه التجربة السريرية هي دراسة المرحلة 1/2 التي ستقيم الحرائك الدوائية وسلامة Etavopivat (FT-4202) في مرضى الأطفال الذين تتراوح أعمارهم بين 12 و 18 عامًا المصابين بمرض الخلايا المنجلية لتحسين كمية الهيموجلوبين في الدم وتقليل العدد من أزمات انسداد الأوعية الدموية (الأوقات التي يتم فيها انسداد الأوعية الدموية وتسبب الألم).
Health conditions/problem studied: Specify
Sickle Cell Disease
Interventions: Specify
Drug: Etavopivat (FT-4202)
Key inclusion and exclusion criteria: Inclusion criteria
Type of Participant and Disease Characteristics 1. Patient has confirmed diagnosis of SCD • Documentation of SCD genotype (HbSS, HbSβ0-thalassemia or other sickle cell syndrome variants) based on prior history of laboratory testing. Molecular genotyping is not required. SCD genotype may be determined from the results of Hb electrophoresis, high-performance liquid chromatography (HPLC), or similar testing. Note that Hb electrophoresis is performed by the local laboratory at Screening. 2. Hemoglobin ≥ 5.5 and < 10.5 g/dL 3. Adolescent patients with severe SCD, as defined by at least 1 of the following: • Two or more VOCs in the past 12 months, defined as a previously documented episode of acute chest syndrome (ACS) or acute painful crisis (for which there was no explanation other than VOC) which required prescription or healthcare professional-instructed use of analgesics for moderate to severe pain • Hospitalization for any SCD-related complication in the last 12 months • Proteinuria, defined as an albumin:creatinine ratio (ACR) > 100 mg/g on 2 measures (separated by ≥ 1 month) as an indicator of early renal disease • History of a conditional TCD in the last 12 months, but not currently being treated with chronic transfusion therapy. Conditional TCD is defined as a TAMMV of 170-199 cm/s by TCD or 155-184 cm/s by imaging TCD (TCDi). 4. For participants taking HU, the dose of HU (mg/kg) must be stable (no more than a 20% change in dosing) for at least 90 days prior to start of study treatment with no anticipated need for dose adjustments during the study, in the opinion of the Investigator 5. Patients on crizanlizumab or L-glutamine treatment at the time of consent may be eligible if they: • Have been on a stable dose for ≥ 12 months at the time of consent (ie, no changes to the dose except for changes to weight or for safety reasons) • For patients on crizanlizumab, have been ≥ 80% compliant
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
12
Key inclusion and exclusion criteria: Age maximum
18
Key inclusion and exclusion criteria: Exclusion criteria
Medical Conditions 1. More than 10 VOCs within the past 12 months that required a hospital, emergency room (ER), or clinic visit 2. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of Screening 3. Abnormal TCD in the prior 12 months Prior/Concomitant Therapy 4. Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) 5. Received any blood products within 30 days of starting study treatment 6. Receiving or use of concomitant medications that are strong inducers of cytochrome P450 (CYP) 3A4/5 within 2 weeks of starting study treatment 7. Use of voxelotor within 28 days prior to starting study treatment or anticipated need for this agent during the study 8. Receipt of erythropoietin or other hematopoietic growth factor treatment within 28 days of starting study treatment or anticipated need for such agents during the study 9. Receipt of prior cellular based therapy (eg, hematopoietic cell transplant, gene modification therapy)
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Other
Trial scope: Specify scope
Pharmacokinetics and Safety
Study design: Allocation
Single Arm Study
Study design: Masking
Open (masking not used)
Study design: Control
Active
Study phase
1 to 2
Study design: Purpose
Treatment
Study design: Assignment
Single
IMP has market authorization
No
Name of IMP
-
Type of IMP
Others
Type of IMP: Specify
Pharmaceutical
Pharmaceutical class
Antianaemics- Pyruvate kinase red blood cell isozyme (PKR) agonist
Therapeutic indication
Sickle Cell Disease
Therapeutic benefit
Etavopivat is an investigational, oral, small molecule activator of erythrocyte pyruvate kinase (PKR) in development for the treatment of sickle cell disease (SCD) and other hemoglobinopathies. PKR activation is proposed to ameliorate the sickling of SCD red blood cells (RBCs) through multiple mechanisms, including reduction of 2,3-diphosphoglycerate (2,3-DPG), which consequently increases hemoglobin (Hb)-oxygen affinity; increased binding of oxygen reduces sickle hemoglobin polymerization and sickling. In addition, PKR activation increases adenosine triphosphate (ATP) produced via glycolytic flux, which helps preserve membrane integrity and RBC deformability.
Biospecimen retention
Samples without DNA
Biospecimen description
PK and PD samples
Target sample size
8
Actual enrollment target size
Date of first enrollment: Type
Anticipated
Date of first enrollment: Date
15/11/2022
Date of study closure: Type
Anticipated
Date of study closure: Date
12/09/2026
Recruitment status
Pending
Date of completion
IPD sharing statement plan
No
IPD sharing statement description
N/A
Additional data URL
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
N/A
N/A
Sources of Monetary or Material Support
Name
Forma Therapeutics, Inc. USA
Secondary Sponsors
Name
N/A
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Mohamed
Salloum
Saint Therese street, Beirut
Lebanon
+961 81967 578
mohamed.salloum@iqvia.com
IQVIA
Scientific
Cameron
Trenor
300 North Beacon Street, Suite 501 Watertown, MA 02472
United States of America
+1-857-209-2374
4202-202Clinical@formarx.com
Forma Therapeutics, Inc.
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Nini Hospital s.a.l.
Dr. Adlette Inati
Hematology
Approved
American University of Beirut Medical Center
Dr. Miguel Abboud
Hematology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
Nini Hospital
26/08/2022
Dr. Elias Bitar
-
+9616431400
American University of Beirut Medical Center
26/01/2023
Dr. Nathalie Zgheib
irb@aub.edu.lb
+961 1 35 00 00 – Ext 5445
Countries of Recruitment
Name
Lebanon
Canada
Health Conditions or Problems Studied
Condition
Code
Keyword
Sickle Cell
Sickle-cell disorders (D57)
Hematology, Blood diseases, Sickle Cell
Interventions
Intervention
Description
Keyword
Drug
Etavopivat (FT-4202)
-
Primary Outcomes
Name
Time points
Measure
To assess the PK of etavopivat in patients with SCD
-
Single-dose: maximum concentration (Cmax), area under the concentration time curve (AUC)0-t, AUC0-inf
To assess the PK of etavopivat in patients with SCD
-
Steady-state etavopivat plasma exposure (Cmax,ss, AUCtau,ss, Cavg,ss, Cmin,ss)
To assess the PK of etavopivat in patients with SCD
-
Estimated using population PK
To assess the safety and tolerability of etavopivat
During the 24-week primary treatment period
Incidence of adverse events (AEs), serious adverse events (SAEs), and AEs related to etavopivat
To assess the safety and tolerability of etavopivat
During the 24-week primary treatment period
Number of premature discontinuations, dose interruptions, and dose reductions
Key Secondary Outcomes
Name
Time points
Measure
To assess the safety and tolerability of etavopivat
during the 72-week treatment extension period
Incidence of AEs, SAEs, and AEs related to etavopivat
To assess the safety and tolerability of etavopivat
during the 72-week treatment extension period
Number of premature discontinuations, dose interruptions, and dose reductions
To assess the effects of etavopivat on hemoglobin (Hb) response
Weeks 12 and 24
Hb response rate (increase of > 1 g/dL from baseline)
To assess the effects of etavopivat on hemoglobin (Hb) response
Weeks 12 and 24
Change in Hb from baseline
To describe occurrence of vaso-occlusive crisis (VOCs) in enrolled patients
-
Change from baseline in incidence of VOCs during the treatment period of: Number of VOCs + Annualized Rate of VOC
To assess changes in fatigue of patients with SCD taking etavopivat
Weeks 12 and 24
Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale
To assess changes in cerebral blood flow in patients with SCD taking etavopivat
-
Change from baseline in time-averaged mean of the maximum velocity (TAMMV) by transcranial Doppler ultrasonography (TCD)
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
Download as PDF
Save a PDF copy of the summary of the trial