Toggle navigation
Lebanon Clinical Trials Registry
Home
About Us
FAQs
Contact Us
Search Trials
Register
Log in
User Guide
Trial details
You are here
Home
Search Trials
Trial details
Trial details
An Adaptive, Randomized, Placebo-controlled, Double-blind, Multi-center Study of Oral FT-4202, a Pyruvate Kinase Activator in Patients with Sickle Cell Disease
Current status:
Approved
|
Date registered:
27/01/2022
Trial version(s)
Current: 10/12/2021
Click here to view the tips and fields' descriptions
Main Information
Primary registry identifying number
LBCTR2021124934
Protocol number
4202-HEM-301
MOH registration number
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Prospective
Date of registration in national regulatory agency
Primary sponsor
Forma Therapeutics, Inc.
Primary sponsor: Country of origin
United Stated of America
Public title
An Adaptive, Randomized, Placebo-controlled, Double-blind, Multi-center Study of Oral FT-4202, a Pyruvate Kinase Activator in Patients with Sickle Cell Disease
Acronym
Scientific title
An Adaptive, Randomized, Placebo-controlled, Double-blind, Multi-center Study of Oral FT-4202, a Pyruvate Kinase Activator in Patients with Sickle Cell Disease
Acronym
Brief summary of the study: English
FT-4202 is an experimental medication that may help treat sickle cell disease by acting to lower the rate of red blood cell (RBC) sickling. RBC sickling can cause hemolysis (breaking apart of RBCs) that leads to anemia and vasoocclusion (painful blockage of blood vessels). This research is being performed to determine the effects of FT-4202, good and bad, in individuals with sickle cell disease. This study is made up of 2 parts: • Double-blind treatment period: Research patients will take the study drug (FT 4202 or placebo, depending on which treatment group they are in) for 52 weeks. This part of the study is “double-blind,” meaning neither the patient nor study doctor will know which specific treatment (FT-4202 or placebo) the patient is receiving. • Open-label extension: Patients who complete the double-blind treatment period may be eligible to receive FT-4202 in the 52-week open-label extension. In this part of the study, the patient will receive FT-4202 even if they were assigned to receive placebo in the double-blind treatment period.
Brief summary of the study: Arabic
FT-4202 عبارة عن دواء تجريبي قد يساعد في علاج مرض الخلايا المنجلية من خلال العمل على خفض معدل خلايا الدم الحمراء المنجلية. يمكن أن تتسبب خلايا الدم الحمراء المنجلية في انحلال الدم والذي يؤدي إلى فقر الدم وانسداد الأوعية الدموية (انسداد مؤلم للأوعية الدموية).يُجرى هذا البحث لتحديد آثار عقار FT-4202، الجيدة والسيئة، على الأشخاص المصابين بمرض الخلايا المنجلية. تتكون هذه الدراسة من جزأين: • فترة العلاج مزدوجة التعمية: سيتناول المرضى المشاركين في البحث عقار الدراسة (FT-4202 أو الدواء الإرضائي، بناءً على مجموعة العلاج المشاركين بها) لمدة 52 أسبوعًا. هذا الجزء من الدراسة "مزدوج التعمية"، مما يعني أنه لن يعرف المريض ولا طبيب الدراسة أي علاج بعينه (FT-4202 أو الدواء الإرضائي) يتلقاه المريض. • فترة التوسع مفتوحة التسمية: قد يكون المرضى الذين يكملون فترة العلاج مزدوجة التعمية مؤهلين لتلقي عقار FT-4202 في فترة التوسع مفتوحة التسمية البالغة 52 أسبوعًا. في هذا الجزء من الدراسة، سيتلقى المريض عقار FT-4202 حتى لو كان تلقي الدواء الإرضائي في فترة العلاج مزدوجة التعمية.
Health conditions/problem studied: Specify
Sickle Cell Disease
Interventions: Specify
Dose Determination Group: In the dose determination portion of the study, up to 90 patients will be randomized in a 1:1:1 ratio to receive FT-4202 low dose (200 mg once daily [QD]), high dose (400 mg QD), or placebo. Patients will be stratified by age (12 to 17, or 18 to 65 years old, inclusive, where applicable), number of VOCs in the preceding 12 months (2 to 3 or 4 to 10), and prior/concomitant hydroxyurea (HU) use in the preceding 12 months (Yes or No). Following randomization, all patients enrolled in the Dose Determination Group will continue blinded treatment for up to a total of 52 weeks. Twelve weeks after the 60th patient has received their first dose of study drug, both safety and Hb response at Week 12 will be unblinded to the Data and Safety Monitoring Board (DSMB) to select the appropriate dose level for further study. Between the time when the 60th patient has received their first dose and the dose determination has been made by the DSMB, enrollment may continue for a maximum of 30 additional patients. After 30 patients are enrolled, enrollment will pause until the dose is selected. Thus, a maximum of 10 patients may be randomized to the unselected dose but not contribute to the dose determination decision. These patients will contribute to the safety analyses. Efficacy Continuation Group: This portion of the study will further establish the efficacy and safety of FT-4202 at the selected dose with planned enrollment up to 274 patients. Patients will be randomized in a 1:1 ratio to receive the selected FT-4202 dose or placebo. Patients will be enrolled using the same inclusion/exclusion criteria and stratified using the same stratification factors in the Dose Determination Group. Open Label Extension Period: All patients, after completion of 52 weeks of double-blind treatment, may enter a 52-week FT-4202 open-label extension period. If some patients in the Dose Determination Group complete 52 weeks of double-blind treatment prior to the DSMB determination of dose selection for the Efficacy Continuation Group, the dose of FT-4202 administered in this open-label extension period will be the high dose of FT-4202. After dose selection by the DSMB at IA1, the dose of FT-4202 administered for all patients in the open-label extension period will be the dose selected for Efficacy Continuation. Patients who do not complete 52 weeks of the double-blinded treatment period may not enter the open-label extension period.
Key inclusion and exclusion criteria: Inclusion criteria
Participants are eligible to be included in the study only if all the following criteria apply: Informed Consent 1. Patient has provided documented informed consent or assent (the informed consent form [ICF] must be reviewed and signed by each patient) Age 2. Age 18 to 65 years, inclusive, at time of randomization Type of Participant and Disease Characteristics 3. Patient has a confirmed diagnosis of sickle cell disease • Documentation of SCD genotype (HbSS, HbSβ0-thalassemia or other sickle cell syndrome variants) based on prior history of laboratory testing; if unavailable, must be confirmed by laboratory testing during screening 4. Patient has had at least 2 episodes of VOC in the past 12 months • For study eligibility, VOC is defined as a previously documented episode of 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 (documentation must exist in the patient medical record prior to Screening) 5. Hemoglobin ≥ 5.5 and ≤ 10 g/dL (≥ 55 and ≤ 100 g/L) during screening 6. 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 Sex and Contraceptive/Barrier Requirements 7. Patients, who if female and of child bearing potential, are using highly effective methods of contraception and agree not to donate ova from study start to 90 days after the last dose of study drug, and who if male are willing to use barrier methods of contraception and agree not to donate sperm, from study start to 90 days after the last dose of study drug
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
65
Key inclusion and exclusion criteria: Exclusion criteria
Patients are excluded from the study if they meet any of the following criteria: Medical Conditions 1. More than 10 VOCs (as defined in Inclusion Criterion 4) within the past 12 months 2. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF 3. Female who is breast feeding or pregnant 4. Hepatic dysfunction characterized by: • Alanine aminotransferase (ALT) > 4.0 × upper limit of normal (ULN) • Direct bilirubin > 3.0 × ULN 5. Patients with clinically significant bacterial, fungal, parasitic, or viral infection requiring systemic therapy • Patients with acute bacterial, fungal, parasitic, or viral infection requiring systemic therapy should delay screening/enrollment until active therapy has been completed Note: Infection prophylaxis is allowed (see concomitant medication restrictions) 6. Known human immunodeficiency virus (HIV) positivity 7. Active infection with hepatitis B virus (hepatitis B surface antigen [HepBsAg] and hepatitis B core antibody [HepBcAb] positive) 8. Active hepatitis C infection 9. Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the central laboratory < 30 mL/min/1.73 m2) or on chronic dialysis 10. History of malignancy within the past 2 years prior to treatment Day 1 requiring systemic chemotherapy and/or radiation • Patients with malignancy considered surgically cured are eligible (eg, non-melanoma skin cancer, cancer of the cervix in-situ, ductal carcinoma in situ [stage 1], grade 1 endometrial cancer) 11. History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following: • Unstable angina pectoris or myocardial infarction or elective coronary intervention • Congestive heart failure requiring hospitalization • Uncontrolled clinically significant arrhythmias • Symptomatic pulmonary hypertension 12. History of overt clinical stroke within previous 2 years or any history of an intracranial hemorrhage 13. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable) 14. Patients with iron deficiency (eg, serum iron less than the lower limit of normal [LLN] or ferritin < 10 μg/L) who are not taking or are unable to take iron supplements at the time of consent and during the study 15. Patients with folate (or folic acid or Vitamin B9) or Vitamin B12 deficiency (eg, folate or Vitamin B12 levels less than the LLN) who are not taking or are unable to take supplements before the first dose of study drug and during the study 16. Patients who are not taking or are unable to take antimalarial prophylaxis at the time of consent and during the study if they live in areas of endemic malaria where prophylaxis is recommended Prior/Concomitant Therapy 17. Patients receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) • Patients who have received an RBC transfusion for any reason within 60 days of the Screening period are eligible if HbA (adult Hb) < 10% by Hb electrophoresis before start of study treatment 18. Receiving or use of concomitant medications that are strong inducers or moderate/strong inhibitors of CYP3A4/5 within 2 weeks of starting study treatment or anticipated need for such agents during the study 19. Use of voxelotor within 28 days prior to starting study treatment or anticipated need for this agent during the study 20. Use of a selectin antagonist (eg, crizanlizumab or other monoclonal antibody or small molecule) within 28 days of starting study treatment or anticipated need for such agents during the study 21. Use of erythropoietin or other hematopoietic growth factor treatment within 28 days of starting study treatment or anticipated need for such agents during the study 22. Receipt of prior cellular-based therapy (eg, hematopoietic cell transplant, gene modification therapy) Prior/Concurrent Clinical Study Experience 23. Participated in another clinical trial of an investigational agent (or medical device) within 28 days or 5 half-lives of first dose of study drug, whichever is longer, or is currently participating in another trial of an investigational agent (or medical device) Other Exclusions 24. Inadequate venous access as determined by the Investigator/ site staff 25. Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
Randomized controlled trial
Study design: Masking
Blinded (masking used)
Study design: Control
Placebo
Study phase
2 to 3
Study design: Purpose
Treatment
Study design: Assignment
Parallel
IMP has market authorization
No
Name of IMP
FT-4202
Type of IMP
Others
Type of IMP: Specify
Chemical
Pharmaceutical class
Small-molecule activator of pyruvate kinase-red blood cell (PKR)
Therapeutic indication
Sickle Cell Disease
Therapeutic benefit
The clinical hypothesis is that PKR activation will reduce the rate of sickle cell polymerization and improve red blood cell (RBC) membrane function, thereby reducing RBC sickling and RBC hemolysis that lead to vascular obstruction and anemia, two hallmarks of SCD pathology.
Biospecimen retention
Samples without DNA
Biospecimen description
Blood and Urine
Target sample size
344
Actual enrollment target size
Date of first enrollment: Type
Anticipated
Date of first enrollment: Date
07/03/2022
Date of study closure: Type
Anticipated
Date of study closure: Date
31/07/2025
Recruitment status
Recruiting
Date of completion
IPD sharing statement plan
No
IPD sharing statement description
NAP
Additional data URL
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
No secondary identifiers
NAP
Sources of Monetary or Material Support
Name
Forma Therapeutics, Inc.
Secondary Sponsors
Name
None
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Reem
Bejjani
Syneos Health, Berytech Technological Pole Mar Roukoz, 1107 2240 Mkalles | Lebanon
Lebanon
+961 4 531 375
reem.bejjani@syneoshealth.com
Syneos Health
Scientific
Adlette
Inati
El Maarad Street, Tripoli
Lebanon
+961 3 228 033
adlette.inati@lau.edu.lb
Nini Hospital
Scientific
Miguel
Abboud
Cairo Street, Beirut
Lebanon
+961 03 534 213
abboudm@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
Nini Hospital
Dr. Adlette Inati
Pediatric Hematology and Oncology Specialist
Approved
American University of Beirut Medical Center
Dr. Miguel Abboud
Pediatric Hematology and Oncology Specialist
Pending
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
Nini Hospital
11/10/2021
Kamleh Ibrahim
kamleh.ibrahim@hopitalnini.com
+961 70 500 375
Countries of Recruitment
Name
Lebanon
France
Germany
Italy
Spain
United Kingdom
Canada
Health Conditions or Problems Studied
Condition
Code
Keyword
Sickle Cell Disease
Sickle-cell disorders (D57)
SCD
Interventions
Intervention
Description
Keyword
Dose Determination Group
90 patients will be randomized in a 1:1:1 ratio to receive FT-4202 low dose (200 mg once daily [QD]), high dose (400 mg QD), or placebo
Dose Determination
Efficacy Continuation Group
Patients will be randomized in a 1:1 ratio to receive the selected FT-4202 dose or placebo.
Efficacy
Open Label Extension Period
The dose of FT-4202 administered in this open-label extension period will be the high dose of FT-4202
OLE
Primary Outcomes
Name
Time points
Measure
To assess the efficacy of FT-4202 in patients with SCD as compared to placebo as measured by improvement in hemoglobin (Hb)
During the blinded treatment period
Hb response rate at Week 24 (increase of > 1 g/dL [> 10 g/L] from baseline)
To assess the efficacy of FT-4202 as compared to placebo on the annualized vaso-occlusive crisis (VOC) rate
During the 52-week blinded treatment period based on adjudicated VOC review
Annualized VOC rate
Key Secondary Outcomes
Name
Time points
Measure
To measure the effects of FT-4202 on clinical measures and sequelae of hemolysis
t Week 24 during the blinded treatment period
Change from baseline in Hb
To measure the effects of FT-4202 on clinical measures and sequelae of hemolysis
At Week 24 during the blinded treatment period
% reticulocytes, Unconjugated bilirubin, and Lactate dehydrogenase (LDH)
To evaluate the effects of FT-4202 on the sequelae of VOC
During the blinded treatment period
Time to first VOC
To assess changes in fatigue of sickle cell patients taking FT-4202
at Week 24 during the blinded treatment period
Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale
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