Safety and efficacy study of roxadustat to treat anemia in patients with lower risk Myelodysplastic Syndrome (MDS), who require 1 to 4 packs of Red Blood Cells through transfusion every 8-weeks.
- Conditions
- Anemia due to Myelodysplastic Syndrome (MDS) in International Prognostic Scoring System – Revised Very Low, Low, or Intermediate Risk with <5% Blasts, and has low red blood cell transfusion burden (requires 1 to 4 packed red blood cell units per 8-week period)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2017-001773-17-ES
- Lead Sponsor
- FibroGen, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 303
1. Diagnosis of primary MDS of >/=16 weeks duration (confirmed by bone marrow aspirate/biopsy within 16 weeks prior to treatment Day 1), classified by the IPSS-R as very low, low, or intermediate risk with <5% bone marrow blasts (documented within 16 weeks prior to randomization).
2. RBC transfusion requirement of either
a. 2 to 4 pRBC over the 8-weeks prior to randomization, or
b. 1 pRBC during the 8-weeks prior to randomization. Patients with 1 pRBC must have a documented history of requiring 1pRBC/8-weeks in 2 consecutive periods of 8 weeks in the 16 weeks preceding registration/randomization
3. No prior use of recombinant erythropoietins or analogues (erythropoiesis-stimulating agents, ESAs), or received a life-time ESA exposure of less than 28 days, AND received no ESA within the 12 weeks prior to day 1 randomization. ESAs include but are not limited to any recombinant human erythropoietin and other drugs listed in Appendix I of the Protocol.
4. Pre-transfusion Hb =/<10.0 g/dL during Screening
5. Age >/=18 years
6. Body weight >/=45 kg
7. ECOG performance status of 0 or 1 at last screen visit
8. Must be capable of giving written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 243
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
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 erythropoietin level >400 mIU/mL
8. Alanine aminotransferase (ALT) AND aspartate aminotransferase (AST) >3 × upper limit of normal (ULN), and total bilirubin (Tbili) > 1.5 × ULN
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
11. Clinically significant anemia 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 antibiotic therapy
13. Cockroft-Gault calculated creatinine clearance <30 mL/min
14. Thromboembolic event (deep vein thrombosis (DVT)), pulmonary embolism, myocardial infarction, stroke, transient ischemic attack (TIA) within previous 6 months
15. Current condition requiring anticoagulants
16. 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
17. Clinically significant or uncontrolled ongoing inflammatory/autoimmune disease (e.g., rheumatoid arthritis, Crohn’s disease, celiac disease, etc.)
18. History of significant liver disease or active liver disease
19. Major surgery planned during the treatment period
20. Known, active or chronic gastrointestinal bleeding
21. Known human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection
22. 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
23. 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 malignancy for at least 5 years) are eligible
24. Previous recipients of roxadustat or another hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method