A randomized, double blind, placebo controlled, multicentre phase 3 trial to evaluate the efficacy and safety of Desidustat for the treatment of chemotherapy induced anemia in patients with solid tumor malignancy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 156
- 试验地点
- 18
- 主要终点
- To assess the efficacy of Desidustat oral tablet in comparison to placebo for the treatment of chemotherapy induced anemia.
研究概览
简要总结
This is a randomized, double blind, placebo controlled, multicentre, phase 3 clinical trial to evaluate the efficacy and safety of Desidustat oral tablets for treatment of chemotherapy induced anemia in patients with solid tumor malignancy. The study consists of screening period of up to 4 weeks, treatment period of 12 weeks, and end of the study visit at Week 14. The total duration of the study will be 126 days including screening period of 28 days.
Informed consent will be obtained from all eligible participants before any study related activity according to the applicable regulatory requirements. After signing the informed consent form, participants will be screened for eligibility to participate in the study based on clinical history, physical examination, vital signs, ECG, and laboratory parameters (hematology, biochemistry, urine analysis, Serum Hepcidin, VEGF, Vitamin B12 and Folic acid, serum beta-HCG, iron profile, and virology tests for HIV type 1 and type 2, HBsAg and Anti-HCV antibody). Eligibility criteria will be assessed at screening (Visit 1) and verified at randomization visit (Visit 2).
Eligible participants will be randomly assigned to either test arm (Desidustat) or comparator arm (matching placebo) with an allocation ratio of 2 and 1. Study drug (test or placebo) will be administered three times a week for a period of 12 weeks with a goal to achieve hemoglobin level within the target of 11 g/dL.
Assessment of hemoglobin level for dose interruption will be done at the site by calibrated HemoCue instrument.
During the study period, dose review and interruption will be permitted every 3 weeks, from visit-3 (Day 21). Dose interruption will be based on hemoglobin level as assessed by change in hemoglobin level compared to previous visit.
If at any visit hemoglobin level is greater than or equals to 12 gm/dl, Desidustat treatment will be interrupted for 21 days, after which hemoglobin assessment would be done with Hemocue, and if the hemoglobin level falls below 11 gm/dl, Desidustat treatment would be re-initiated. if not therapy would be interrupted till next scheduled visit.
During the study, participants will be followed up at the study sites for 7 scheduled visits.
At screening visit (Visit 1 - Day - 28)
Randomization visit (Visit 2 - Day 0)
Follow-up visits during the treatment period
Visit 3 (Day 21 plus or minus 3 days), Visit 4 (Day 42 plus or minus 3 days), Visit 5 (Day 63 plus or minus 3 days), Visit 6 (Day 84 plus or minus 3 days)
Safety follow-up (Visit 7, Day 98 plus or minus 3 days) will be conducted after 2 weeks (within allowable window period) of EOT period.
During the follow-up visits, participants will be evaluated for efficacy and safety.
Evaluation of efficacy will be done by assessing mean change in hemoglobin level from baseline to Week 12 in Desidustat arm compared to placebo arm.
Additional efficacy assessment will be done by assessing mean of maximum increase in hemoglobin level in Desidustat arm from baseline to Week 12 without rescue therapy in comparison to placebo arm.
Efficacy will be assessed by proportion of participants achieving Hemoglobin response and requiring rescue therapy.
Median time to achieve target hemoglobin level ( greater than or equals to 11 g/dL) and mean change from baseline to Week 12 in serum hepcidin level, serum VEGF level will also be evaluated.
To evaluate the safety, participants will be assessed by physical examination, vital signs, ECG, and safety laboratory parameters as described in the schedule of assessments.
All the participants will be evaluated for adverse events throughout the study period. If further investigations are required in case of any AE, investigator is advised to assess the AE and take necessary action. Participants are advised to contact the investigator for any discomfort.
To ensure the safety of the trial participants, an oversight on interim safety data was provided by the independent data and safety monitoring board (DSMB ). Interim safety data of first 24 participants up to 21 days after randomization was presented to the independent DSMB in blinded manner. Unanimous decision of continuation of the trial was provided by DSMB members on 24th December 2025.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •Adult male and female (Age greater than or equals to 18)
- •Body weight greater than or equals to 45 kg at screening
- •Confirmed diagnosis of solid tumor malignancy (based on historical document such as histopathology report and current documentation of the disease by imaging modality performed within 03 months prior to screening
- •Anemia caused by myelosuppressive chemotherapy defined as hemoglobin level 8 to 10 g/dL (both inclusive) assessed at screening (Patient must have received at least one cycle of myelosuppressive chemotherapy irrespective of the treatment regimen within 28 days prior to screening) (Refer Annexure No. III)
- •ECOG performance status of 0 to 2 at screening
- •Planned concurrent treatment of cancer with myelosuppressive chemotherapy for at least 08 additional weeks irrespective of frequency of cycles
- •Estimated life expectancy greater than or equals to 6 months at enrolment
- •Adequate iron status defined as serum Ferritin level greater than or equals to 100 ng/mL and transferrin saturation (TSAT) greater than or equals to 20 percent at screening.
- •Men and women of childbearing potential must agree to use adequate birth control measures during the study. Acceptable methods of birth control in this study include.
- •surgical sterilization, intrauterine device, oral contraceptive, contraceptive patch, long-acting injectable contraceptive, partners vasectomy, double-barrier method (condom or diaphragm with spermicide) during study participation and for 30 days after their last dose of study drug.
- •Participants must be capable of giving written informed consent. Understand and sign informed consent be willing to comply with all study procedures. In case of illiterate patients, thumb impression of the patients will be obtained along with the signature of the impartial witness on the consent form prior to patients participation in the trial.
排除标准
- •Patients who are receiving only hormonal products, novel immunosuppressive therapy, or targeted biological therapy or radiation therapy to treat their cancer
- •Patients who have received an RBC transfusion or erythropoietin therapy within 4 weeks prior to randomization
- •Patients who preferred a red blood cell (RBC) transfusion for treatment of anemia at time of study entry over receiving the study drug (Desidustat)
- •Participants who have participated in clinical trial of any investigational product or medical device within 3 months prior to screening other than the present trial.
- •Clinically significant Vitamin B12 or Folic acid deficiency assessed at screening
- •Serologic status assessed at screening that reflect active infection with HBV, HCV or HIV.
- •Female participants with any of one of the following criteria: a.
- •History of pregnancy or lactation within three months prior to screening b.
- •Positive serum beta-HCG test at screening c.
- •History of amenorrhea for less than 1 year and not using adequate antifertility measures
- •Abnormal baseline laboratory investigations as follows: a.
- •Total WBC count less than or equals to 2 x 103/microL b.
- •Absolute Neutrophil Count less than or equals to 1000/microL d.
- •ALT and/or AST greater than or equals to 2.5 times of the ULN and Total bilirubin greater than 1.5 times of ULN In participants with metastatic lesions in liver, AST/ALT level greater than 5 times ULN shall be excluded e.
- •Total bilirubin greater than 2 times of ULN f.
- •HbA1c greater than 9 percent
- •History of significant heart disease, including New York Heart Association 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
- •History of thromboembolic event (deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke, or transient ischemic attack) within previous 6 months prior to screening
- •History of leukemia
- •History of clinically significant anemia due to other aetiologies such autoimmune or hereditary hemolysis or anemia, hemorrhage, or hereditary anemia such as sickle cell anemia or thalassemia
- •Clinically significant or uncontrolled ongoing autoimmune disease (e.g., rheumatoid arthritis, Crohns disease, celiac disease, etc.)
- •Major surgery within 90 days prior to randomization, and minor surgery within 30 days of prior to randomization or planned surgery during the study period
- •History of severe allergic or hypersensitivity reaction to investigational products and its excipients
- •Medical, psychological or behavioural conditions, which in the opinion of the investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent.
- •History of significant alcoholism or drug abuse within the past 1 year.
- •History or presence of significant smoking (more than 10 cigarettes per day) or consumption of tobacco/nicotine products (more than 10 times per day).
- •Unable to swallow tablets or disease significantly affected gastrointestinal function and/or inhibiting small intestine absorption such as; malabsorption syndrome, resection of the small bowel or poorly controlled inflammatory bowel disease affecting the small intestine.
- •Clinically significant abnormal findings on physical examination, or 12-lead ECG at screening
- •Current life-threatening illness, medical condition or organ system dysfunction which, in the Investigators opinion, could compromise the patients safety.
- •Presence of other systemic disorders or diseases (e.g., respiratory, gastrointestinal, endocrine, immunological, dermatological, neurological, psychiatric disease or any other body system involvement) which, in the Investigators opinion, could compromise the patients safety.
- •Active infection requiring chronic antibiotic therapy.
- •Presence or a history of bleeding disorders or clinical conditions (e.g. gastrointestinal (GI) bleeding or constitutional disorders) that may increase risk of life-threatening bleeding.
- •Any condition not mentioned in any of the above criteria that, as per the investigator, would hinder participation of subject in the study.
结局指标
主要结局
To assess the efficacy of Desidustat oral tablet in comparison to placebo for the treatment of chemotherapy induced anemia.
时间窗: Mean change in hemoglobin level - Week 12
次要结局
- A. To evaluate the additional and indirect parameters of efficacy of Desidustat oral tablet compared to placebo.(B. To evaluate safety of Desidustat oral tablet compared to placebo during the trial.)
研究者
Dr Dharmesh Domadia
Cliantha Research Limited