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CTRI Number  CTRI/2021/03/031725 [Registered on: 04/03/2021] Trial Registered Prospectively
Last Modified On: 31/07/2023
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   Efficacy and Safety of FG-4592 for Treatment of Anaemia in Patients with Lower Risk Myelodysplastic Syndrome (MDS) with Low Red Blood Cell Transfusion Burden 
Scientific Title of Study   A Phase 3 Randomized Double-Blind Placebo-Controlled Study Investigating the Efficacy and Safety of Roxadustat (FG-4592) for Treatment of Anemia in Patients with Lower Risk Myelodysplastic Syndrome (MDS) with Low Red Blood Cell (RBC) Transfusion Burden (LTB) 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
129546  Other 
2017-001773-17  EudraCT 
FGCL-4592-082 (version 3.0, 30-Jan-2020)  Protocol Number 
NCT03263091  ClinicalTrials.gov 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name   
Designation   
Affiliation   
Address 




 
Phone    
Fax    
Email    
 
Details of Contact Person
Scientific Query  
Name  Dr Annappa Kamath 
Designation  Senior Solutions Consultant Director 
Affiliation  PAREXEL International Clinical Research Private Limited 
Address  CRS SOLUTION CONSULTANTS Department
CoWrks, Coworking Spaces Pvt. Ltd. – RMZ Eco World, Ground Floor, Bay Area – Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village.
Bangalore
KARNATAKA
560103
India 
Phone  918067169360  
Fax  918067723001  
Email  Annappa.Kamath@PAREXEL.com  
 
Details of Contact Person
Public Query  
Name  Dr Annappa Kamath 
Designation  Senior Solutions Consultant Director 
Affiliation  PAREXEL International Clinical Research Private Limited 
Address  CRS SOLUTION CONSULTANTS Department
CoWrks, Coworking Spaces Pvt. Ltd. – RMZ Eco World, Ground Floor, Bay Area – Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village.
Bangalore
KARNATAKA
560103
India 
Phone  918067169360  
Fax  918067723001  
Email  Annappa.Kamath@PAREXEL.com  
 
Source of Monetary or Material Support  
FibroGen, Inc, 409 Illinois Street, San Francisco, California 94158, USA 
 
Primary Sponsor  
Name  FibroGen Inc 
Address  409 Illinois Street San Francisco California 94158 USA 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
Parexel International Clinical Research Private Limited  CoWrks, Coworking Spaces Pvt. Ltd-RMZ Eco World, Ground Floor, Bay Area - Adjacent to Building 6A, Outer Ring Road, Devarabeesanahalli Village, BENGALURU, INDIA - 560103 
 
Countries of Recruitment
Modification(s)  		   Republic of Korea
Australia
Belgium
Canada
Denmark
France
Germany
India
Israel
Italy
Poland
Russian Federation
Spain
Turkey
United Kingdom
United States of America
Norway  
Sites of Study
Modification(s)  
No of Sites = 2  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Biju George  "Christian Medical College"  Department of Hematology, OT block, First floor, room # 03, Ida Scudder Road, Vellore-632004.
Vellore
TAMIL NADU 		 04162282352

biju@cmcvellore.ac.in 
Dr Tuphan Kanti Dolai  "Nilratan Sircar Medical College Hospital"  Department of Hematology, HOD’s Chamber, 4th floor, Nilratan Sircar Medical College Hospital, 138, AJC Bose Road, Kolkata 700014.
Kolkata
WEST BENGAL 		 9874890275

tkdolai@hotmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 2  
Name of Committee  Approval Status 
"NRS Medical College and Hospital"  Approved 
"Silver Institutional Review Board"  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: D469||Myelodysplastic syndrome, unspecified,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Roxadustat  Roxadustat will be administered as an oral route at a dose of 50mg per kg body weight 
Comparator Agent  Placebo  Placebo will be administered as an oral route 
Intervention  Roxadustat  Roxadustat will be administered as an oral route at a dose of 100 mg per kg body weight 
Intervention  Roxadustat  Roxadustat will be administered as an oral route at a dose of 150 mg per kg body weight 
Intervention  Roxadustat  Roxadustat will be administered as an oral route at a dose of 20mg per kg body weight 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  1.Diagnosis of primary MDS (confirmed by bone marrow aspirate and biopsy prior to Treatment Day 1)classified by the IPSS-R as very low, low, or intermediate risk with <5% bone marrow blasts. There is no minimum time from diagnosis to registration/randomization except to allow for proper IPSS-R classification to be made (within 16 weeks prior to randomization), and to show transfusion dependence for patients in both portions of the study.
2.RBC transfusion requirement of either:
a)2 to 4 pRBC during the 8-weeks prior to registration/randomization,
b)1 pRBC during the 8-weeks prior to registration/randomization: Patients with 1 pRBC must have a documented history of requiring 1 pRBC/8-weeks in 2 consecutive periods of 8 weeks in the 16 weeks preceding registration/randomization (The PI and site staff will utilize their own institutional criteria for the determination of when to transfuse a patient.
c)Open-Label Lead-in patients only, the requirement to demonstrate transfusion dependence can also be met by a PI starting this particular patient on pRBC transfusion during the screening period.
3.There is no restriction on prior use of recombinant erythropoietins or analogues (erythropoiesis-stimulating agents (ESAs)), except that the patient must not have received any ESA within the 8 weeks prior to Day 1. registration/randomization. ESAs include but are not limited to any recombinant human erythropoietin and other drugs listed in Appendix I of the protocol #FGCL-4592-082 dated 30-Jan-2020.
4.Hb ≤10.0 g/dL during Screening, Only 1 central laboratory value needs to meet the Hb ≤ 10.0 g/dL criteria.
5.Age ≥18 years.
6.Body weight ≥45 kg.
7.ECOG performance status of 0, 1 or 2 during screening.
8.Must be capable of giving written informed consent 
 
ExclusionCriteria 
Details  1.Diagnosis of secondary MDS associated with prior chemotherapy, extensive radiation therapy (>25% of bone marrow reserve), and or/other significant chemical or radiation exposure
2.Previous diagnosis of IPSS-R high risk or very high risk MDS (Appendix G)
3.Planned myeloablative or craniospinal radiation during the study
4.Prior bone marrow or stem cell transplantation (SCT)
5.Significant myelofibrosis (>2+ fibrosis)
6.MDS associated with 5q(del) cytogenetic abnormality
7.Screen serum erythropoietin level: >400 mIU/mL;
Amendment 03: Patients with elevated serum erythropoietin levels (>400 mIU/mL) are allowed to repeat after ≥ 7 days. If the serum erythropoietin remains elevated (>400 mIU/mL) the patient may then qualify for the OL High-erythropoietin cohort.
8.Alanine aminotransferase (ALT) >3 x upper limit of normal (ULN), OR aspartate aminotransferase (AST) >3 × ULN, OR total bilirubin (TBili) > 1.5 × ULN.
Amendment 03: Patients with TBili up to 2.0 x ULN may be allowed to participate if the AST and ALT are within normal limits.
9.Azacitidine, decitabine, thalidomide, lenalidomide, granulocyte colony-stimulating factor (G-CSF), or luspatercept, or any investigational drugs within 8-weeks prior to Day 1 Treatment or plans to use any of these medications during the course of clinical trial participation
10.Anticipated use of dapsone at any dose amount or chronic use of acetaminophen or paracetamol > 2.0 g/day during the study for more than 7 days
11.Clinically significant anemia, as determined by the investigator, due to non-MDS etiologies such as iron deficiency, vitamin B12 or folate deficiency, autoimmune or hereditary hemolysis or anemia or hemorrhage or hereditary anemia such as sickle cell anemia or thalassemia
12.Active infection(s) requiring systemic antibiotic therapy (upon treatment with antibiotic, stable asymptomatic patients may qualify to participate.)
13.Cockroft-Gault calculated estimated glomerular filtration rate (eGFR) <30 mL/min
14.Thromboembolic event (such as deep vein thrombosis (DVT)), pulmonary embolism, myocardial infarction, stroke, or transient ischemic attack (TIA), within previous 6 months of randomization
15.Significant heart disease, including New York Heart Association (NYHA) Class III or IV congestive heart failure, uncontrolled hypertension or hypotension, or significant valvular or endocardial disease that would put the patient at risk for thromboembolism
16.Clinically significant or uncontrolled ongoing inflammatory/autoimmune disease (e.g., rheumatoid arthritis, Crohn’s disease, celiac disease, etc.)
17.History of significant liver disease or active liver disease
18.Major surgery planned during the treatment period
19.Known, active or chronic gastrointestinal bleeding
20. Known human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection.
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant and Investigator Blinded 
Primary Outcome  
Outcome  TimePoints 
"Efficacy of roxadustat (FG-4592) to achieve transfusion independence ≥ 56 consecutive days"  "28 weeks" 
 
Secondary Outcome  
Outcome  TimePoints 
Evaluate the incidence of treatment emergent adverse events of roxadustat
 		 52 weeks  
Effect of roxadustat on quality of life parameters as measured by PROMIS and EQ 5D 5L assessment
 		 52 weeks 
Evaluate transfusion independence greater than 56 or equal to consecutive days
 		 52 weeks 
Evaluate the impact of roxadustat on RBC transfusion requirements  52 weeks 
 
Target Sample Size
Modification(s)  		 Total Sample Size="204"
Sample Size from India="15" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   15/03/2021 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  22/02/2018 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="5"
Months="5"
Days="25" 
Recruitment Status of Trial (Global)
Modification(s)  		 Other (Terminated) 
Recruitment Status of Trial (India)  Other (Terminated) 
Publication Details   None 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary   The purpose of this study is to determine whether is safe and effective in the treatment of anemia in patients with Lower Risk Myelodysplastic Syndrome and Low Red Blood Cell Transfusion Burden


Due to word limits in the exclusion criteria section remaining few points were added below,

1.Clinically significant or uncontrolled medical condition that would affect the patient’s ability to participate in the study or confound the study’s efficacy or safety results
2.History of leukemia or other active malignancy except localized and non-metastatic squamous or basal cell carcinoma of the skin, or cervical intraepithelial neoplasm; patients with a history of cured malignancy with no evidence of recurrence for at least 3 years are eligible
3.Previous recipient of roxadustat or another hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI)
4.Pregnant or breastfeeding females
• Additional central laboratory samples may be collected via unscheduled visit to confirm eligibility, as deemed necessary by the investigator. Medical monitor should be informed.
• A positive Hep-C test will be confirmed via C-RNA testing; C-RNA negative patient may qualify to participate.
• Patients must meet all eligibility criteria prior to randomization; no waiver will be granted.
 
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