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)
Conditions
Sponsors
FibroGen, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 =65 years) yes F.1.3.1 Number of subjects for this age range 243
Exclusion criteria
Exclusion criteria: 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 serum erythropoietin level > 400 mIU/mL Patients with elevated serum rythropoietin 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 Higherythropoietin cohort. 8. Alanine aminotransferase (ALT) > 3 x ULN, OR aspartate aminotransferase (AST) > 3 × ULN OR TBili > 1.5 × ULN 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 DVT, pulmonary embolism, myocardial infarction, stroke, or TIA, within previous 6 months of randomization 15. Exclusion criteria 15 has been removed 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 recurrence for at least 3 years are eligible 24. Previous recipient of roxadustat or another hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) 25. Pregnant or breastfeeding females -Additional central laboratory samples may be collected via unscheduled visit to confirm eligibility, as deemed necessary by the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of roxadustat in the treatment of anemia in patients with lower risk MDS who have a low burden of RBC transfusion. ;Secondary Objective: - To evaluate the safety of roxadustat - To evaluate the impact of roxadustat on RBC transfusion requirements - To evaluate pharmacokinetics (PK) and pharmacodynamics (PD) of roxadustat in MDS patients - To evaluate effect of roxadustat on quality of life parameters;Primary end point(s): The primary efficacy endpoint is the proportion of patients who achieved transfusion-independence (TI) =56 consecutive days in the first 28 weeks of treatment;Timepoint(s) of evaluation of this end point: The first 28 weeks of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Proportion of patients achieved TI =56 consecutive days anytime during the study - Proportion of patients who achieved =50% reduction in number of RBC transfusion over any 8 weeks compared to their baseline - Cumulative number of patient-exposure-week of TI - Number of pRBC packs transfused compared to baseline - Proportion of patients who achieved TI for =20 Weeks (140 Days) - Mean change from baseline in Physical Function as measured by Patient Reported Outcomes Measurement Information System (PROMIS) - Mean change from baseline in PROMIS Fatigue score. - Mean change from baseline in Euroqol Quality of Life Five Dimensional Five Level Health Questionnaire (EQ-5D-5L) assessment;Timepoint(s) of evaluation of this end point: All secondary and exploratory endpoints will be analyzed at both for the first 28 weeks of treatment and for the end of the 52-week study treatment period, if appropriate. | — |
Countries
Australia, Belgium, Canada, Denmark, France, Germany, Israel, Italy, Korea, Republic of, Netherlands, Poland, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Development
FibroGen, Inc.
Outcome results
None listed