Anaemia Associated With Chronic Kidney Disease Clinical Trial
Official title:
Open-Label Randomised Controlled Trial of Efepoetin Alfa for Treatment of Anaemia Associated With Chronic Kidney Disease Patients Not on Dialysis (ND-CKD). A Non- Inferiority Trial Compared to Methoxy Polyethylene Glycol-Epoetin Beta (MIRCERA)
Verified date | December 2023 |
Source | PT Kalbe Genexine Biologics |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This is an open-label, randomised, multicenter, Mircera-controlled, parallel-group, Phase III study to determine whether subcutaneous administered efepoetin alfa is as effective and well tolerated as subcutaneous Mircera for anaemia correction and maintenance in erythropoiesis stimulating agent (ESA)-naïve subjects who have CKD and are not on dialysis. ESA prior users who have stopped using ESA at least 12 weeks till screening will also be eligible for this study provided they fulfil all the subject entry criteria.
Status | Completed |
Enrollment | 391 |
Est. completion date | June 30, 2023 |
Est. primary completion date | March 30, 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Age should be greater than or equal to the minimum age of consent in the applicable country 2. Stage 3 or 4 CKD (eGFR = 15 and < 60 mL/min/1.73 m2) 3. ESA-naive (no prior ESA use) subjects whose Hb at baseline is = 8 g/dL and < 10 g/dL, or ESA prior users whose Hb at baseline is = 8 g/dL and < 10 g/dL and who have stopped using ESA at least 12 weeks till the screening 4. Ferritin = 100 ng/mL and transferrin saturation (TSAT) = 20% 5. Subject must be willing to complete all study-related activities and follow-up visits 6. Evidence of a signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. Exclusion Criteria: 1. Need for dialysis therapy expected in the next 12 months or rapid progression of CKD (e.g., eGFR decrease of >20% within 12 weeks) 2. Received a blood transfusion (including RBC transfusion) within the 12 weeks prior to screening, or blood transfusion is anticipated during the study period 3. Have a history of overt gastrointestinal bleeding or any other bleeding episode associated with a fall in Hb of = 1 g/dL, within the last 8 weeks prior to screening 4. Have an unstable Hb for any reason, in the investigator's opinion 5. Have non-renal anaemia (any anaemia where the investigator considers the anaemia is predominantly due to a non-renal cause. Non-renal causes include, but are not limited to vitamin B12 or folic acid deficiency, homozygous sickle-cell disease, thalassemia of all types, other non-renal cause of anaemia such as myelodysplasia or haematological malignancies) 6. Platelet count of = 50 x109/L 7. Vitamin B12 deficiency defined as total serum levels of < 181 pmol/L (246 pg/ml) 10 8. Folic acid deficiency defined as total serum levels < 7.63 nmol/L (3.37 ng/mL) 10 9. Pure red cell aplasia, or a history of pure red cell aplasia 10. Poorly controlled hypertension defined as a sitting SBP =170 mmHg and/or DBP =100 mm Hg 11. Chronic congestive heart failure (New York Heart Association class IV) or are otherwise at high risk for early withdrawal or interruption of the study (due to myocardial infarction, severe or unstable coronary artery disease, stroke, or severe liver disease) within the 12 weeks before screening or during screening 12. Active or not active malignancy (except non-melanoma skin cancer) within five years before screening 13. Planned live kidney transplantation scheduled within 52 weeks after the screening visit 14. Uncontrolled hyperparathyroidism, in the investigator's opinion 15. Uncontrolled hypothyroidism determined by the investigator that they cannot participate in the study 16. Active acute or chronic infection, or uncontrolled or symptomatic inflammatory disease (e.g., rheumatoid arthritis, systemic lupus erythematosus), or a C-reactive protein level > 15 mg/L. (Routinely screening for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infection is not required in this protocol. By history or current clinical evidence, patients with active acute HBV or HCV infection should be excluded. Chronic HBV/HCV infection with LFTs > 3 times of normal are excluded. Known HIV positive patients are excluded) 17. Immunosuppressive therapy (other than corticosteroids for a chronic condition, or tacrolimus/cyclosporine) within 12 weeks prior to baseline 18. Life expectancy of less than 52 weeks 19. Planned surgery during the study period (excluding minor skin excisions) 20. Have received investigational drug(s) other than those of this study within 4 weeks prior to screening, or will receive investigational drug(s) other than those of this study during the study period 21. History or clinical evidence of cardiovascular, haematologic or hepatic (ALT, AST, bilirubin values above three times the upper limit of normal [ULN] at screening) or any physical conditions that, in the opinion of the investigator, would compromise participation in the study 22. With a cognitive or psychiatric condition rendering the subject unable to be cooperative with and complete study requirements 23. Hypersensitivity to any one of the investigational drugs 24. Subjects are, in the judgement of the investigator, otherwise inappropriate for entry into the study 25. Subjects who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or subjects who are KGBio or CRO employees directly involved in the conduct of the trial 26. Participation in other studies involving same investigational drug(s) (Phases 1-4) of this study within 12 weeks before screening 27. Females of childbearing potential or males who are unable/unwilling to take adequate contraceptive precautions defined by the protocol for the duration of the study and for at least 28 days after last dose of investigational product. Females have a positive pregnancy test result within 24 hours prior to study entry, is otherwise known to be pregnant, plans to become pregnant in the next 12 months or is currently breastfeeding. |
Country | Name | City | State |
---|---|---|---|
Australia | Royal Adelaide Hospital | Adelaide | South Australia |
Australia | Renal Research Gosford | Gosford | New South Wales |
Australia | Launceston General Hospital | Launceston | Tasmania |
Indonesia | Rspad Gatot Soebroto | Jakarta Pusat | |
Indonesia | Rumah Sakit Islam Jakarta Cempaka Putih | Jakarta Pusat | |
Indonesia | Rumah Sakit Islam Jakarta Pondok Kopi | Jakarta Pusat | |
Indonesia | Rumah Sakit Pgi Cikini | Jakarta Pusat | |
Indonesia | Rumah Sakit Umum Pusat Fatmawati | Jakarta Pusat | |
Indonesia | Rumah Sakit Umum Pusat Nasional Dr Cipto Mangunkusumo | Jakarta Pusat | |
Korea, Republic of | Chungnam National University Hospital | Daejeon | |
Korea, Republic of | Korea University Ansan Hospital | Gyeonggi-do | |
Korea, Republic of | Seoul National University Bundang Hospital | Gyeonggi-do | |
Korea, Republic of | The Catholic University of Korea Incheon St. Mary'S Hospital | Incheon | |
Korea, Republic of | Chungnam National University Sejong Hospital | Sejong | |
Korea, Republic of | Kyung Hee University Hospital At Gangdong | Seoul | |
Korea, Republic of | The Catholic University of Korea Eunpyeong St. Mary'S Hospital | Seoul | |
Korea, Republic of | The Catholic University of Korea Seoul St. Mary'S Hospital | Seoul | |
Korea, Republic of | The Catholic University of Korea, Yeouido St. Mary'S Hospital | Seoul | |
Malaysia | Hospital Raja Permaisuri Bainun | Ipoh | |
Malaysia | Hospital Kajang | Kajang | |
Malaysia | Hospital Raja Perempuan Zainab II | Kota Bharu | |
Malaysia | Hospital Kuala Lumpur | Kuala Lumpur | |
Malaysia | University of Malaya Medical Centre | Kuala Lumpur | Selangor |
Malaysia | Hospital Tengku Ampuan Afzan | Kuantan | |
Malaysia | Hospital Serdang | Serdang | |
Malaysia | Seri Manjung Hospital | Seri Manjung | Perak |
Malaysia | Hospital Sibu | Sibu | |
Philippines | M3 Dialysis Center | Bacolod City | |
Philippines | Baguio General Hospital Medical Center | Baguio | |
Philippines | Norzel Medical and Diagnostic Clinic | Cebu City | |
Philippines | De La Salle Medical and Health Sciences Institute | Dasmariñas | |
Philippines | Davao Doctors Hospital | Davao City | |
Philippines | West Visayas State University Hospital | Iloilo City | |
Philippines | National Kidney and Transplant Institute | Quezon | |
Taiwan | Changhua Christian Hospital | Changhua | |
Taiwan | Hualien Tzu Chi Hospital | Hualien City | |
Taiwan | Kaohsiung Chang Gung Hospital | Kaohsiung | |
Taiwan | Kaohsiung Medical University Chung-Ho Memorial Hospital | Kaohsiung | |
Taiwan | Kaohsiung Veterans General Hospital | Kaohsiung | |
Taiwan | Keelung Chang Gung Memorial Hospital | Keelung | |
Taiwan | Kuang Tien General Hospital | Taichung | |
Taiwan | Taiching Veterans General Hospital | Taichung | |
Taiwan | Chi Mei Medical Center | Tainan | |
Taiwan | National Cheng Kung University Hospital | Tainan | |
Taiwan | Far Eastern Memorial Hospital | Taipei | |
Taiwan | National Taiwan University Hospital | Taipei | |
Taiwan | Taipei Medical University - Shuang Ho Hospital | Taipei | |
Taiwan | Tri-Service General Hospital | Taipei | |
Taiwan | Linkou Chang Gung Memorial Hospital | Taoyuan | |
Thailand | Siriraj Hospital | Bangkok | |
Thailand | Vajira Hospital | Bangkok | |
Thailand | Maharaj Nakorn Chiang Mai Hospital | Chiang Mai | |
Thailand | Thammasat University Hospital | Pathum Thani | |
Thailand | Songklanagarind Hospital | Songkhla | |
Thailand | Sunpasitthiprasong Hospital | Ubon Ratchathani |
Lead Sponsor | Collaborator |
---|---|
PT Kalbe Genexine Biologics | Novotech (Australia) Pty Limited |
Australia, Indonesia, Korea, Republic of, Malaysia, Philippines, Taiwan, Thailand,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | To assess the efficacy of efepoetin alfa in the treatment of anaemia associated with CKD as measured by haemoglobin (Hb) response rate at the end of correction treatment evaluation period | Measurement is done by an increase in Hb more than or equal to 1 g/dL compared with baseline and a Hb concentration within range of 10 - 12 g/dL inclusive without transfusion during evaluation period | Measurement from the date of Randomization till the End of the Corrective Treatment period, assessed up to 20 weeks. | |
Secondary | Characterise safety and tolerability of subcutaneous efepoetin alfa is being measured by based on the frequency of adverse events and on the number of out of range laboratory values. | Safety endpoints parameters including Serious Adverse Events (SAE) specified below Composite outcome of cardiovascular death or a nonfatal myocardial infarction or stroke All-cause mortality Cardiovascular mortality Acute myocardial infarction Heart failure Acute kidney injury defined according to Acute Kidney Injury Network (AKIN) criteria Abnormal clinical laboratory tests (haematology, biochemistry including serum ferritin and TSAT) Anti-efepoetin alfa or anti-Mircera antibody titres Clinically meaningful abnormal findings of vital signs Development of clinically meaningful electrocardiogram abnormalities Hospitalisations (excluding those for logistic reasons) It is a composite outcome. Any abnormal test findings during the study will be helpful in reviewing the outcome. |
Measurement from the time the subject provides informed consent through and including 28 calendar days after the last study drug administration. |