CTRI/2021/03/031725Other3 期
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)
试验速览
- 阶段
- 3 期
- 状态
- Other
- 发起方
- FibroGen Inc
- 入组人数
- 204
- 试验地点
- 2
- 主要终点
- "Efficacy of roxadustat (FG-4592) to achieve transfusion independence ≥ 56 consecutive days"
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •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
- •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-
- •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.
排除标准
- •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
- •Known human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection.
结局指标
主要结局
"Efficacy of roxadustat (FG-4592) to achieve transfusion independence ≥ 56 consecutive days"
时间窗: "28 weeks"
次要结局
- Evaluate the incidence of treatment emergent adverse events of roxadustat
- Effect of roxadustat on quality of life parameters as measured by PROMIS and EQ 5D 5L assessment
- Evaluate transfusion independence greater than 56 or equal to consecutive days
- Evaluate the impact of roxadustat on RBC transfusion requirements(52 weeks)
研究者
研究点 (2)
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