EFEPOETIN ALFA for Anemia due to chronic kidney disease on dialysis

Inclusion criteria

• {"criterion_text":"- Adult males and females ≥ 18 years old.\n- Serum total vitamin B12 concentrations ≥LLN at screening.\n- 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\n- Patient with stage 4 and 5 CKD defined by estimated GFR (eGFR, ≤29 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.\n- Hemodialysis patients with single-pool Kt/V ≥ 1.2 or urea reduction ratio ≥ 65%.\n- 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\n- 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.\n- Patients with serum ferritin ≥100 ng/mL at screening.\n- Patients with transferrin saturation (TSAT) ≥20% at screening.\n- Serum folate concentrations ≥lower limit of normal (LLN) at screening."}

Exclusion criteria

• {"criterion_text":"- 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).\n- 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\n- Chronic congestive heart failure (New York Heart Association class III or IV).\n- 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.\n- 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.\n- Uncontrolled hypertension defined as a sitting systolic blood pressure ≥170 mmHg and/or diastolic blood pressure ≥100 mmHg (measure BP in both arms, then the arm that gives the higher reading for subsequent readings).\n- 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.\n- 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.\n- 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.\n- Any prior functioning organ transplant or a scheduled organ transplantation, or anephric state (one or both kidneys).\n- Planned elective surgery that could lead to significant blood loss during the study period.\n- 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).\n- Hypoalbuminemia (Serum albumin <2.5 g/dL) at Screening Visit.\n- Androgen, deferoxamine, deferiprone, or deferasirox therapy within 12 weeks prior to Day 1.\n- Life expectancy of <12 months.\n- Cognitive or psychiatric condition rendering the patient unable to be cooperative with and complete study requirements.\n- Hypersensitivity to any one of the investigational drugs or its excipients.\n- Patients with very limited functional capacity for which a target Hb value of 12 g/dL may have a lower benefit/risk ratio.\n- Immunosuppressive therapy (tacrolimus/cyclosporine, and other than corticosteroids for a chronic condition) within 12 weeks prior to Day 1.\n- 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.\n- History of alcohol or drug abuse within the past 2 years and inability to avoid consumption of more than >3 alcoholic beverages per day.\n- Use of an investigational medication or treatment, participation in an investigational interventional study, or carryover effect of an investigational treatment expected during the study.\n- 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.\n- 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.\n- 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."}

Primary endpoints

• {"endpoint_text":"- The 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) within 6 weeks prior to and during the 8-week evaluation period. Baseline value is defined as the mean of the last screening value and Day1 (Visit 2) value.","definition_or_measurement_approach":"Mean change from Baseline in hemoglobin (Hb) averaged over Week 20 to Week 28. Rescue therapy (transfusion or any approved ESA) within 6 weeks prior to and during the 8-week evaluation period excludes measurements; Baseline is defined as the mean of the last screening value and Day 1 (Visit 2) value."}

Secondary endpoints

• {"endpoint_text":"- Mean change from Baseline in Hb averaged over Week 20 to Week 28, regardless of whether the patient received rescue therapy.\n- Mean change from Baseline in Hb level averaged over the maintenance period, regardless of whether the patient received rescue therapy\n- Proportion of patients who maintain Hb level at 10.0-12.0 g/dL over Week 20 to Week 28*, and over the maintenance period, regardless of whether the patient received rescue therapy.\n- Proportion of patients with mean Hb ≥ 10.0 g/dL averaged over Week 20 to Week 28*, and over the maintenance period, regardless of whether the patient received rescue therapy.\n- Proportion of patients requiring rescue therapy during study treatment and time to rescue therapy from date of first dose of study treatment.\n- Proportion of patients receiving rescue therapy over Week 20 to Week 28, and over the maintenance period.\n- Mean dose of the IP over Week 20 to Week 28, and over the maintenance period.\n- Mean change in QoL from Day 1 (V2) over time assessed through the 36-Item Health Survey 1.0 Questionnaire (Rand SF-36).","definition_or_measurement_approach":"Endpoints are defined as changes from Baseline in Hb over specified periods (Week 20-28 and maintenance), proportions maintaining target Hb ranges, rescue therapy usage and timing, mean dose of investigational product over specified periods, and QoL assessed by the RAND SF-36 questionnaire. Some secondary endpoints specify assessment regardless of rescue therapy; details of exact timepoints and analysis windows are provided in the endpoint texts."}

Bulgaria

Earliest CTIS Part Ii Submission Date

16-10-2023

Latest Decision Or Authorization Date

11-02-2024

Processing Time Days

118

Number Of Sites

10

Number Of Participants

50

Czechia

Earliest CTIS Part Ii Submission Date

24-01-2024

Latest Decision Or Authorization Date

09-02-2024

Processing Time Days

16

Number Of Sites

4

Number Of Participants

30

Hungary

Earliest CTIS Part Ii Submission Date

24-01-2024

Latest Decision Or Authorization Date

08-02-2024

Processing Time Days

15

Number Of Sites

5

Number Of Participants

42

Italy

Earliest CTIS Part Ii Submission Date

24-01-2024

Latest Decision Or Authorization Date

09-02-2024

Processing Time Days

16

Number Of Sites

9

Number Of Participants

45

Poland

Earliest CTIS Part Ii Submission Date

26-01-2024

Latest Decision Or Authorization Date

09-02-2024

Processing Time Days

14

Number Of Sites

10

Number Of Participants

55

Primary sponsor

Full Name

Genexine Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Korea, Republic of

Contract research organisations

Name

Opis S.r.l.

Responsibilities

Documentation management and archiving, Pharmacovigilance, Quality management, Management of payments to institutions (sponsor duties codes present)

Name

MARKEN Germany GmbH

Responsibilities

Provide ADA lab kits

Name

Almac Clinical Services Limited

Responsibilities

sponsor duties code 14 (role text not provided in record)

Third parties

• {"country":"Italy","full_name":"Opis S.r.l.","duties_or_roles":"Codes: 1,10,11,12,13,15,5,6,7,8; text for code 15 provided: Documentation management and archiving, Pharmacovigilance, Quality management, Management of payments to institutions","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"MARKEN Germany GmbH","duties_or_roles":"Code: 15; value: Provide ADA lab kits","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"Code: 14","organisation_type":"Pharmaceutical company"}