Clinical trial NCT04155125: A Study of Efepoetin Alfa in Treating Anaemia Associated With Chronic Kidney Diseases Patient
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anaemia Associated With Chronic Kidney Disease
Lead sponsor: PT Kalbe Genexine Biologics
Sponsor class: INDUSTRY
Collaborators: name: Novotech (Australia) Pty Limited
First posted: 2019-11-07
Enrollment: 391
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: The study will consist of a 20-week correction period for dosage titration and Hb correction, followed by an 8-week evaluation period for efficacy assessments of corrective treatment. Subjects who respond to efepoetin alfa (defined as an increase in Hb ≥1.0 g/dL versus baseline and Hb level within 10 - 12 g/dL range without blood transfusion during the 28 weeks after the first dose) will be eligible to continue treatment, and will be randomised to receive subcutaneous efepoetin alfa either once every 2W or every 4W for an additional 24-week extension period to assess long-term safety and maintenance effect. Mircera responders will also be allowed to continue the drug during the extension period, receiving it every 4 weeks using the dose equal to twice the previous once-every-two-week dose. The safety data collected will be part of an ongoing pooled analysis of safety data from the efepoetin alfa clinical development program.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Measurement from the date of Randomization till the End of the Corrective Treatment period, assessed up to 20 weeks.
Secondary outcomes:
measure: 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.
timeFrame: Measurement from the time the subject provides informed consent through and including 28 calendar days after the last study drug administration.
Other outcomes:
Locations:
city: Gosford
country: Australia
facility: Renal Research Gosford
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Launceston
country: Australia
facility: Launceston General Hospital
state: Tasmania
city: Jakarta Pusat
country: Indonesia
facility: Rspad Gatot Soebroto
city: Jakarta Pusat
country: Indonesia
facility: Rumah Sakit Islam Jakarta Cempaka Putih
city: Jakarta Pusat
country: Indonesia
facility: Rumah Sakit Islam Jakarta Pondok Kopi
city: Jakarta Pusat
country: Indonesia
facility: Rumah Sakit Pgi Cikini
city: Jakarta Pusat
country: Indonesia
facility: Rumah Sakit Umum Pusat Fatmawati
city: Jakarta Pusat
country: Indonesia
facility: Rumah Sakit Umum Pusat Nasional Dr Cipto Mangunkusumo
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Incheon
country: Korea, Republic of
facility: The Catholic University of Korea Incheon St. Mary'S Hospital
city: Sejong
country: Korea, Republic of
facility: Chungnam National University Sejong Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital At Gangdong
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Eunpyeong St. Mary'S Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St. Mary'S Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Yeouido St. Mary'S Hospital
city: Seri Manjung
country: Malaysia
facility: Seri Manjung Hospital
state: Perak
city: Kuala Lumpur
country: Malaysia
facility: University of Malaya Medical Centre
state: Selangor
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
city: Kajang
country: Malaysia
facility: Hospital Kajang
city: Kota Bharu
country: Malaysia
facility: Hospital Raja Perempuan Zainab II
city: Kuala Lumpur
country: Malaysia
facility: Hospital Kuala Lumpur
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan
city: Serdang
country: Malaysia
facility: Hospital Serdang
city: Sibu
country: Malaysia
facility: Hospital Sibu
city: Bacolod City
country: Philippines
facility: M3 Dialysis Center
city: Baguio
country: Philippines
facility: Baguio General Hospital Medical Center
city: Cebu City
country: Philippines
facility: Norzel Medical and Diagnostic Clinic
city: Dasmariñas
country: Philippines
facility: De La Salle Medical and Health Sciences Institute
city: Davao City
country: Philippines
facility: Davao Doctors Hospital
city: Iloilo City
country: Philippines
facility: West Visayas State University Hospital
city: Quezon
country: Philippines
facility: National Kidney and Transplant Institute
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Hualien City
country: Taiwan
facility: Hualien Tzu Chi Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Hospital
city: Keelung
country: Taiwan
facility: Keelung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: Taiching Veterans General Hospital
city: Taichung
country: Taiwan
facility: Kuang Tien General Hospital
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Taipei
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University - Shuang Ho Hospital
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
city: Bangkok
country: Thailand
facility: Vajira Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Pathum Thani
country: Thailand
facility: Thammasat University Hospital
city: Songkhla
country: Thailand
facility: Songklanagarind Hospital
city: Ubon Ratchathani
country: Thailand
facility: Sunpasitthiprasong Hospital
Study officials:
References: