A Study of Efepoetin Alfa in Treating Anaemia Associated With Chronic Kidney Diseases Patient

NCT ID: NCT04155125

Last Updated: 2023-12-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 391 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-02
• Study Completion Date: 2023-06-30

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.

Conditions

Anaemia Associated With Chronic Kidney Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

efepoetin alfa

Route of administration: Subcutaneous Injection.

The administration interval and initial dosage for subjects who are randomly assigned to subcutaneous efepoetin alfa will be starting from 4 μg/kg BW once per 2 weeks, then titrated based on Hb level during study period.

Group Type: EXPERIMENTAL

efepoetin alfa

Intervention Type: DRUG

The administration interval and initial dosage for subjects who are randomly assigned to subcutaneous efepoetin alfa will be starting from 4 μg/kg BW once per 2 weeks, then titrated based on Hb level during study period.

Mircera

Route of administration: Subcutaneous Injection.

The starting dosage of Mircera arm will be 0.6 μg/kg BW per 2 weeks based on prior data in similar study populations with subsequent titration to achieve targeted Hb range. During the correction treatment period, the dosage of study drug will be adjusted to achieve a Hb level range within 10 - 12 g/dL and an increase ≥1.0 g/dL versus the individual patient's baseline Hb level. During the extension period, Hb levels should be maintained between 10 and 12 g/dL.

Group Type: PLACEBO_COMPARATOR

Mircera

Intervention Type: DRUG

The starting dosage of Mircera arm will be 0.6 μg/kg BW per 2 weeks based on prior data in similar study populations with subsequent titration to achieve targeted Hb range. During the correction treatment period, the dosage of study drug will be adjusted to achieve a Hb level range within 10 - 12 g/dL and an increase ≥1.0 g/dL versus the individual patient's baseline Hb level. During the extension period, Hb levels should be maintained between 10 and 12 g/dL.

Interventions

efepoetin alfa

The administration interval and initial dosage for subjects who are randomly assigned to subcutaneous efepoetin alfa will be starting from 4 μg/kg BW once per 2 weeks, then titrated based on Hb level during study period.

Intervention Type: DRUG

Mircera

The starting dosage of Mircera arm will be 0.6 μg/kg BW per 2 weeks based on prior data in similar study populations with subsequent titration to achieve targeted Hb range. During the correction treatment period, the dosage of study drug will be adjusted to achieve a Hb level range within 10 - 12 g/dL and an increase ≥1.0 g/dL versus the individual patient's baseline Hb level. During the extension period, Hb levels should be maintained between 10 and 12 g/dL.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novotech (Australia) Pty Limited

INDUSTRY

Sponsor Role: collaborator

PT Kalbe Genexine Biologics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Renal Research Gosford

Gosford, New South Wales, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Launceston General Hospital

Launceston, Tasmania, Australia

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, , Indonesia

Seri Manjung Hospital

Seri Manjung, Perak, Malaysia

University of Malaya Medical Centre

Kuala Lumpur, Selangor, 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

Hospital Tengku Ampuan Afzan

Kuantan, , Malaysia

Hospital Serdang

Serdang, , Malaysia

Hospital Sibu

Sibu, , Malaysia

M3 Dialysis Center

Bacolod City, , Philippines

Baguio General Hospital Medical Center

Baguio City, , 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, , Philippines

Chungnam National University Hospital

Daejeon, , South Korea

Korea University Ansan Hospital

Gyeonggi-do, , South Korea

Seoul National University Bundang Hospital

Gyeonggi-do, , South Korea

The Catholic University of Korea Incheon St. Mary'S Hospital

Incheon, , South Korea

Chungnam National University Sejong Hospital

Sejong, , South Korea

Kyung Hee University Hospital At Gangdong

Seoul, , South Korea

The Catholic University of Korea Eunpyeong St. Mary'S Hospital

Seoul, , South Korea

The Catholic University of Korea Seoul St. Mary'S Hospital

Seoul, , South Korea

The Catholic University of Korea, Yeouido St. Mary'S Hospital

Seoul, , South Korea

Changhua Christian Hospital

Changhua, , Taiwan

Hualien Tzu Chi Hospital

Hualien City, , Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Kaohsiung Veterans General Hospital

Kaohsiung City, , Taiwan

Kaohsiung Chang Gung Hospital

Kaohsiung City, , Taiwan

Keelung Chang Gung Memorial Hospital

Keelung, , Taiwan

Taiching Veterans General Hospital

Taichung, , Taiwan

Kuang Tien General Hospital

Taichung, , Taiwan

Chi Mei Medical Center

Tainan City, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Tri-Service General Hospital

Taipei, , Taiwan

Far Eastern Memorial Hospital

Taipei, , Taiwan

Taipei Medical University - Shuang Ho Hospital

Taipei, , Taiwan

Linkou Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

Vajira Hospital

Bangkok, , Thailand

Siriraj 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, , Thailand

Countries

Australia; Indonesia; Malaysia; Philippines; South Korea; Taiwan; Thailand

Other Identifiers

GXE4KGBio-001

Identifier Type: -

Identifier Source: org_study_id