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

Официальное название

A Phase III, Randomized, Investigator-Blinded, Active-Controlled Study of Efficacy and Safety of Efepoetin Alfa for Treatment of Anemia in Patients With Chronic Kidney Disease on Dialysis

Обзор

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

Подробное описание

This is an investigator-blinded, randomized, multicenter, active-controlled Phase III study for the treatment of anemia in patients with CKD on hemodialysis. Eligible patients will be randomized to efepoetin alfa or darbepoetin alfa at a ratio of 2:1. An unblinded team will prepare and administer the study drug at the dosages decided by the blinded Investigator.

The study consists of 3 study periods:

* Screening (up to 28 days before Day 1): subjects in screening will continue treatment with epoetin, methoxy polyethylene glycol-epoetin beta, or darbepoetin alfa as per local standard of care. * Treatment: subjects will discontinue any prior erythropoietin analogue and will be randomized to switch to efepoetin alfa or darbepoetin alfa in a 2:1 ratio.

The aim of the treatment period is to maintain Hb levels between 10.0 g/dL and 12.0 g/dL. It is recommended that study treatment be administered any time after completion of dialysis if dosing is scheduled on a dialysis day to avoid potential bias on study assessments.

• Follow-up (4 weeks) Phone contacts can be done for follow-up for up to Week 56 or at the time of the last patient's Week 56 visit, whichever is shorter.

Вмешательства

• Препарат Efepoetin Alfa
  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 a
• Препарат Darbepoetin Alfa
  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 cance

Первичные конечные точки

• Mean change in hemoglobin (Hb) [Срок оценки: Over Week 20 to Week 28]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.
• Hypoalbuminemia (Serum albumin <2.5 g/dL) at Screening Visit.
• Androgen, deferoxamine, deferiprone, or deferasirox therapy within 12 weeks prior to Day 1.
• Life expectancy of <12 months.
• Cognitive or psychiatric condition rendering the patient unable to be cooperative with and complete study requirements.
• Hypersensitivity to any one of the investigational drugs or its excipients.
• Received a blood transfusion (including RBC transfusion) within the 12 weeks prior to Screening, or blood transfusion is anticipated during the study period (excluding temporary blood transfusion given in case of blood loss due to accident or surgery).
• Immunosuppressive therapy (tacrolimus/cyclosporine, and other than corticosteroids for a chronic condition) within 12 weeks prior to Day 1.
• History of alcohol or drug abuse within the past 2 years and inability to avoid consumption of more than >3 alcoholic beverages per day.
• Use of an investigational medication or treatment, participation in an investigational interventional study, or carryover effect of an investigational treatment expected during the study.
• 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 4 months for male subjects and 7 months for female patients after the end of the study. Females with a positive pregnancy test result within 24 hours prior to study entry, are otherwise known to be pregnant, plan to become pregnant in the next 12 months or are currently breastfeeding.
• Patients 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 patients who are Sponsor or clinical research organization (CRO) employees directly involved in the conduct of the study.
• Patients with very limited functional capacity for which a target Hb value of 12 g/dL may have a lower benefit/risk ratio.
• Any medical condition (patients weighing over 150 kg) that, in the opinion of the Investigator, may pose a safety risk to a patient in this study, may confound efficacy or safety assessment, or may interfere with study participation

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Болгария · 13 центров

• Multiprofile Hospital for Active Treatment Puls AD — Blagoevgrad
• Department of Dialysis Treatment, Multiprofile Hospital for Active Treatment - Dobrich AD, — Dobrich
• Department of Nephrology, Dialysis Treatment, Multiprofile Hospital for Active Treatment " — Gabrovo
• First Dialysis Services Bulgaria EAD, branck Montana — Montana
• Diaslys Center - Pazardzhik — Pazardzhik
• Department of Dialysis Treatment, Multiprofile Hospital for Active Treatment - Plovdiv AD, — Plovdiv
• First Dialysis Services Bulgaria EAD, Plovdiv — Plovdiv
• Department of Dialysis Treatment, University Multiprofile Hospital for Active Treatment "M — Rousse
• … и ещё 5 центров

Польша · 8 центров

• Wojewodzki Szpital Specjalistyczny im. Kazimierza Dluskiego w Bialymstoku — Bialystok
• DaVita Stacja Dializ Brodnica — Brodnica
• Samodzielny Publiczny Zakład Opieki Zdrowotnej Centralny Szpital Kliniczny Uniwersytetu Me — Lodz
• DaVita Sp. z o.o. Pszczyna — Pszczyna
• DaVita Stacja Dializ WADOWICE — Wadowice
• DaVita sp. z o.o. Warszawa Mangalia — Warsaw
• DaVita Stacja Dializ Warszawa — Warsaw
• DaVita Sp. z o.o. Zyrardow — Żyrardów

Италия · 7 центров

• Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia- Unità Operati — Brescia
• SODc Nefrologia Dialisi Trapianto Azienda Ospedaliero Universitaria Careggi — Florence
• "Azienda Ospedaliero Universitaria ""Ospedali Riuniti"" di Foggia Unità Operativa Compless — Foggia
• IRCCS Ospedale Policlinico San Martino — Genova
• ICS Maugeri — Pavia
• AOU Pisana UO Nefrologia Trapianti e Dialisi — Pisa
• AOU Integrata di Verona UOC Nefrologia — Verona

South Korea · 5 центров

• Korea University Ansan Hospital — Ansan
• St Mary's Incheon Hospital — Incheon
• Kangdong KyungHee University Hospital — Seoul
• St Mary's Seoul Hospital — Seoul
• St Mary's Yeouido Hospital — Seoul

Чехия · 4 центра

• Nemocnice Cesky krumlov — Český Krumlov
• Nemocnice Havlíčkův Brod — Havlíčkův Brod
• HDS Privamed Healthia sro v Plzni — Pilsen
• B. Braun Avitum s.r.o - Dialyzacni stredisko Teplice - Nefrologicka ambulance — Teplice

Грузия · 4 центра

• Batumi Dialysis and Nephrology Center — Batumi
• Clinical Center for Nephrology Development — Tbilisi
• L.Managadze National Center of Urology — Tbilisi
• Tbilisi Heart And Vascular Clinic — Tbilisi

Индонезия · 4 центра

• RSUP Dr. Hasan Sadikin — Bandung
• RS Islam Jakarta Cempaka Putih — Jakarta
• RSPAD Gatot Soebroto — Jakarta
• RSUPN Dr. Cipto Mangunkusumo — Jakarta

Тайвань · 4 центра

• Hualien Tzu Chi Hospital — Hualien City
• Far Eastern Memorial Hospital — New Taipei City
• Shuang Ho Hospital — New Taipei City
• Taipei Medical University Hospital — Taipei

Армения · 3 центра

• "ARABKIR" Joint Medical Center & Institute of Child and Adolescent Health — Yerevan
• "BEST LIFE" Medical Center Armenian-Japanese Joint Venture LLC — Yerevan
• 'Astghik'' Medical Center — Yerevan

Сербия · 3 центра

• Clinic for Nephrology, Clinical Hospital Center Zvezdara — Belgrade
• Clinic for Nephrology and Dialysis, University Clinical Center Kragujevac — Kragujevac
• Clinic for Nephrology and Dialysis, University Clinical Center Nis — Niš

Turkey (Türkiye) · 3 центра

• Ege University Faculty of Medicine Hospital — Izmir
• Erciyes University Faculty of Medicine Hospital — Kayseri
• Kocaeli University Faculty of Medicine Hospital — Kocaeli

Идентификаторы

NCT: NCT06466785 · GX-E4-CKD-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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