A Phase 3 Study of Efepoetin Alfa for Treatment of Anemia in Patients With Chronic Kidney Disease on Dialysis

NCT06466785 | Recruiting Phase 3 DMC

• 1 other identifier: GX-E4-CKD-002
• Study Type: interventional
• Target: 429
• Locations: 2 countries
• Sites: 9

Brief Summary

An investigator-blinded, randomized, multicenter, active-controlled Phase III study for the treatment of anemia in patients with CKD on hemodialysis

Conditions

Anemia of Chronic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• Mean change in hemoglobin (Hb)

  Mean change from Baseline in Hb averaged over Week 20 to Week 28 without the use of rescue therapy (i.e., transfusion, or any approved ESA for all patients) within 6 weeks prior to and during the 8-week evaluation period.

  Over Week 20 to Week 28

Study Arms (2)

Efepoetin Alfa (GX-E4)

EXPERIMENTAL

Dose: 0.3 mg/0.3 mL, 0.6 mg/0.6 mL and 1 mg/1 mL pre-filled syringe (PFS) solution. The dose of study drug can be varied depending on the level of Hb. Frequency: Efepoetin alfa should be administered at 1-week intervals from Day 1 (Visit 2) to Week 28 (Visit 30), but the administration interval may be changed to 1 or 2 weeks from Week 29 (Visit 31) to Week 52 (Visit 54) according to the investigator's judgement. Mode of administration: intravenous injection. When the dose of investigational product (IP) is planned on the same day as hemodialysis (HD), the IP should be injected at the end of HD.

Drug: Efepoetin Alfa

Darbepoetin Alfa (Aranesp®)

ACTIVE COMPARATOR

Dose: 20 µg/0.5 mL, 30 µg/0.3 mL, 60 µg/0.3 mL, 100 μg/0.5 mL PFS. The dose of comparator drug can be varied depending on the level of Hb. Frequency: Darbepoetin alfa should be administered at 1-week intervals from Day 1 (Visit 2) to Week 28 (Visit 30), but the administration interval may be changed to 1 or 2 weeks from Week 29 (Visit 31) to Week 52 (Visit 54) according to the investigator's judgement. Mode of administration: intravenous injection.

Drug: Darbepoetin Alfa

Interventions

Efepoetin Alfa DRUG

Efepoetin alfa (Epoetin-Fc fusion protein, GX-E2 or GX-E4,) is a novel long-acting erythropoietin-hybrid fragment crystallizable (Fc) fusion protein developed by Genexine, intended for treatment and maintenance of anemia due to CKD with or without dialysis. Its drug substance is a recombinant form of human EPO and hybrid Fc (hyFc®) fragment consisting of 2 subunits with a total of 411 amino acid residues. Each subunit contains an EPO molecule linked to a hybrid Fc fragment of c terminal of CH2 and CH3 regions from IgG4 and to N-terminal of CH2 region and the hinge sequence from IgD. These 2 subunits are joined by a single disulfide bond at the hinge region of each subunit. Half-life is 138.5-157.9 hours. It is an acidic glycoprotein of about 30 kDa and comprises 165 amino acids and 4 glycans. Circulating EPO exhibits several glycosylation isoforms that differ in electrical charge and biological activity

Also known as: GX-E4

Efepoetin Alfa (GX-E4)

Darbepoetin Alfa DRUG

Darbepoetin alfa is a re-engineered form of erythropoietin containing 5 amino acid changes (N30, T32, V87, N88, T90) resulting in the creation of 2 new sites for N-linked carbohydrate addition. It has a 3-fold longer serum half-life compared to epoetin alpha and epoetin beta. It stimulates erythropoiesis (increases red blood cell levels) by the same mechanism as rHuEpo (binding and activating the Epo receptor) and is used to treat anemia, commonly associated with chronic kidney failure and cancer chemotherapy

Also known as: Aranesp®

Darbepoetin Alfa (Aranesp®)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males and females ≥ 18 years old.
• Patient (or patient's legally acceptable representative) has voluntarily signed and dated an informed consent form (ICF), approved by an Ethics Committee (EC) or institutional review board (IRB), after the nature of the study has been explained and the patient has had the opportunity to ask questions.
• Patient with stage 5 CKD defined by estimated GFR (eGFR, ≤15 mL/min/1.73m2) on adequate HD for a minimum of 12 weeks prior to Day 1. \*CKD staging will be based on the five-stage system for classification of CKD based on KDIGO guidelines.
• Hemodialysis patients with single-pool Kt/V ≥ 1.2 or urea reduction ratio ≥ 65%.
• \*Single-pool Kt/V or urea reduction ratio will be based on results measured within 4 weeks prior to screening or during the screening period.
• Patients must be on stable doses of IV injections of ESA (including biosimilars) for at least 6 weeks prior to Day 1.
• Minimum ESA dose;
• Epoetin alfa, epoetin beta, and epoetin kappa: ≥1,500 U/week
• Darbepoetin alfa: ≥20 µg/week
• Mircera®: ≥30 µg/2 weeks
• Mean of the 2 most recent local laboratory Hb screening values obtained at least 6 days apart, must be 9.0 g/dL to 12.0 g/dL, inclusive, with a difference of ≤1.5 g/dL between the highest and the lowest value.
• Patients with serum ferritin ≥100 ng/mL at screening.
• Patients with transferrin saturation (TSAT) ≥20% at screening.
• Serum folate concentrations ≥lower limit of normal (LLN) at screening.
• Serum total vitamin B12 concentrations ≥LLN at screening.

You may not qualify if:

• Active acute or chronic infection, or uncontrolled or symptomatic inflammatory disease other than glomerulonephritis that could impact erythropoiesis (e.g., systemic lupus erythematosus, rheumatoid arthritis, celiac disease), or a C reactive protein level 40\> mg/L (high sensitive C-reactive protein level \> 10 mg/L).
• By history or current clinical evidence, patients with active acute hepatitis B virus (HBV) or hepatitis C virus (HCV) infection should be excluded. Routine screening for HBV, HCV, and human immunodeficiency virus (HIV) infection is not required in this protocol. Chronic HBV/HCV infection with liver function tests (LFT) \>3 times of normal are excluded. Known HIV positive patients are excluded.
• History or clinical evidence of cardiovascular, hematologic, hepatic, or any physical conditions that, in the opinion of the Investigator, would compromise participation in the study.
• Any of the following laboratory abnormalities at screening visit;
• Alanine transaminase (ALT) \>3 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) \>3 x ULN
• Total bilirubin \>1.5 x ULN
• Chronic congestive heart failure (New York Heart Association class III or IV).
• 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.
• Uncontrolled hypertension defined as a sitting systolic blood pressure ≥170 mmHg and/or diastolic blood pressure ≥100 mmHg.
• History of active malignancy except for cancers determined to be cured or in remission for ≥5 years, curatively resected basal cell or squamous cell skin cancers, or in situ cancer at any site.
• Patients with 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.
• Known history of myelodysplastic syndrome, multiple myeloma, hereditary hematologic disease such as thalassemia, sickle cell anemia, pure red cell aplasia, or other known causes for anemia other than CKD, hemosiderosis, hemochromatosis, known coagulation disorder, or hypercoagulable condition.
• Any prior functioning organ transplant or a scheduled organ transplantation, or anephric state (one or both kidneys).
• Planned elective surgery that could lead to significant blood loss during the study period.

Sponsors & Collaborators

• Genexine, Inc.: lead
• PT Kalbe Genexine Biologics: collaborator

Study Sites (9)

Batumi Dialysis and Nephrology Center

Batumi, Georgia

RECRUITING

Clinical Center for Nephrology Development

Tbilisi, Georgia

RECRUITING

L.Managadze National Center of Urology

Tbilisi, Georgia

RECRUITING

Tbilisi Heart And Vascular Clinic

Tbilisi, Georgia

RECRUITING

Korea University Ansan Hospital

Ansan, South Korea

RECRUITING

St Mary's Incheon Hospital

Incheon, South Korea

RECRUITING

Kangdong KyungHee University Hospital

Seoul, South Korea

RECRUITING

St Mary's Seoul Hospital

Seoul, South Korea

RECRUITING

St Mary's Yeouido Hospital

Seoul, South Korea

RECRUITING

MeSH Terms

Interventions

Darbepoetin alfa

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Yoon-Jeong Choi

  Genexine, Inc.

  STUDY DIRECTOR

Central Study Contacts

Yoon-Jeong Choi

CONTACT

+82-2-6098-2756; yoonjeong.choi@genexine.com

TaeKyung Seong

CONTACT

+82-2-6098-2759; taekyung.seong@genexine.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2024
• First Posted: June 20, 2024
• Study Start: January 25, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: June 24, 2024

Record last verified: 2024-06

Locations

GE (4); KR (5)