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: 11 countries
• Sites: 58

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 (58)

"ARABKIR" Joint Medical Center & Institute of Child and Adolescent Health

Yerevan, Armenia

RECRUITING

"BEST LIFE" Medical Center Armenian-Japanese Joint Venture LLC

Yerevan, Armenia

RECRUITING

'Astghik'' Medical Center

Yerevan, Armenia

RECRUITING

Multiprofile Hospital for Active Treatment Puls AD

Blagoevgrad, Bulgaria

RECRUITING

Department of Dialysis Treatment, Multiprofile Hospital for Active Treatment - Dobrich AD, Dobrich

Dobrich, Bulgaria

RECRUITING

Department of Nephrology, Dialysis Treatment, Multiprofile Hospital for Active Treatment "Dr. Tota Venkova" AD, Gabrovo

Gabrovo, Bulgaria

RECRUITING

First Dialysis Services Bulgaria EAD, branck Montana

Montana, Bulgaria

RECRUITING

Diaslys Center - Pazardzhik

Pazardzhik, Bulgaria

RECRUITING

Department of Dialysis Treatment, Multiprofile Hospital for Active Treatment - Plovdiv AD, Plovdiv

Plovdiv, Bulgaria

RECRUITING

First Dialysis Services Bulgaria EAD, Plovdiv

Plovdiv, Bulgaria

RECRUITING

Department of Dialysis Treatment, University Multiprofile Hospital for Active Treatment "Medica Ruse" OOD, Ruse

Rousse, Bulgaria

RECRUITING

Department of Dialysis Treatment, Multiprofile Hospital for Active Treatment "Dr. Ivan Selimski - Sliven" AD, Sliven

Sliven, Bulgaria

RECRUITING

Acibadem CityClinic UMHAT Tokuda EAD

Sofia, Bulgaria

RECRUITING

Dialysis Center - Dialmed

Sofia, Bulgaria

RECRUITING

Dialysis Center Hemomed EOOD

Sofia, Bulgaria

RECRUITING

Multiprofile Hospital for Active Treatment Sveta Anna - Varna AD

Varna, Bulgaria

RECRUITING

Nemocnice Cesky krumlov

Český Krumlov, Czechia

RECRUITING

Nemocnice Havlíčkův Brod

Havlíčkův Brod, Czechia

RECRUITING

HDS Privamed Healthia sro v Plzni

Pilsen, Czechia

RECRUITING

B. Braun Avitum s.r.o - Dialyzacni stredisko Teplice - Nefrologicka ambulance

Teplice, Czechia

RECRUITING

Batumi Dialysis and Nephrology Center

Batumi, Georgia

COMPLETED

Clinical Center for Nephrology Development

Tbilisi, Georgia

COMPLETED

L.Managadze National Center of Urology

Tbilisi, Georgia

COMPLETED

Tbilisi Heart And Vascular Clinic

Tbilisi, Georgia

COMPLETED

RSUP Dr. Hasan Sadikin

Bandung, Indonesia

COMPLETED

RS Islam Jakarta Cempaka Putih

Jakarta, Indonesia

COMPLETED

RSPAD Gatot Soebroto

Jakarta, Indonesia

COMPLETED

RSUPN Dr. Cipto Mangunkusumo

Jakarta, Indonesia

COMPLETED

Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia- Unità Operativa (UO) Nefrologia

Brescia, Italy

RECRUITING

SODc Nefrologia Dialisi Trapianto Azienda Ospedaliero Universitaria Careggi

Florence, Italy

RECRUITING

"Azienda Ospedaliero Universitaria ""Ospedali Riuniti"" di Foggia Unità Operativa Complessa di Nefrologia, Dialisi e Trapianto"

Foggia, Italy

RECRUITING

IRCCS Ospedale Policlinico San Martino

Genova, Italy

RECRUITING

ICS Maugeri

Pavia, Italy

RECRUITING

AOU Pisana UO Nefrologia Trapianti e Dialisi

Pisa, Italy

RECRUITING

AOU Integrata di Verona UOC Nefrologia

Verona, Italy

RECRUITING

Wojewodzki Szpital Specjalistyczny im. Kazimierza Dluskiego w Bialymstoku

Bialystok, Poland

RECRUITING

DaVita Stacja Dializ Brodnica

Brodnica, Poland

RECRUITING

Samodzielny Publiczny Zakład Opieki Zdrowotnej Centralny Szpital Kliniczny Uniwersytetu Medycznego w Łodzi

Lodz, Poland

RECRUITING

DaVita Sp. z o.o. Pszczyna

Pszczyna, Poland

RECRUITING

DaVita Stacja Dializ WADOWICE

Wadowice, Poland

RECRUITING

DaVita sp. z o.o. Warszawa Mangalia

Warsaw, Poland

RECRUITING

DaVita Stacja Dializ Warszawa

Warsaw, Poland

RECRUITING

DaVita Sp. z o.o. Zyrardow

Żyrardów, Poland

RECRUITING

Clinic for Nephrology, Clinical Hospital Center Zvezdara

Belgrade, Serbia

RECRUITING

Clinic for Nephrology and Dialysis, University Clinical Center Kragujevac

Kragujevac, Serbia

RECRUITING

Clinic for Nephrology and Dialysis, University Clinical Center Nis

Niš, Serbia

RECRUITING

Korea University Ansan Hospital

Ansan, South Korea

COMPLETED

St Mary's Incheon Hospital

Incheon, South Korea

COMPLETED

Kangdong KyungHee University Hospital

Seoul, South Korea

COMPLETED

St Mary's Seoul Hospital

Seoul, South Korea

COMPLETED

St Mary's Yeouido Hospital

Seoul, South Korea

COMPLETED

Hualien Tzu Chi Hospital

Hualien City, Taiwan

RECRUITING

Far Eastern Memorial Hospital

New Taipei City, Taiwan

RECRUITING

Shuang Ho Hospital

New Taipei City, Taiwan

RECRUITING

Taipei Medical University Hospital

Taipei, Taiwan

RECRUITING

Ege University Faculty of Medicine Hospital

Izmir, Turkey (Türkiye)

COMPLETED

Erciyes University Faculty of Medicine Hospital

Kayseri, Turkey (Türkiye)

COMPLETED

Kocaeli University Faculty of Medicine Hospital

Kocaeli, Turkey (Türkiye)

COMPLETED

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): June 1, 2027
• Study Completion (Estimated): March 1, 2028
• Last Updated: May 22, 2026

Record last verified: 2026-05

Locations

GE (4); BU (13); TU (3); PL (8); TW (4); ID (4); AR (3); CZ (4); SE (3); IT (7); KR (5)