Efepoetin alfa for treatment of anemia in chronic kidney disease on dialysis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genexine Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2024-02-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

To evaluate the efficacy of efepoetin alfa compared to darbepoetin alfa in terms of hemoglobin (Hb) level control (non-inferiority) in hemodialysis patients with anemia due to chronic kidney disease (CKD).

Secondary objectives 8

1. To compare the change from baseline in Hb level over the maintenance period (starts at Week 29 and can last up to Week 52) between treatment groups.
2. To compare the proportion of patients who maintained a mean Hb level of 10.0 12.0 g/dL over Week 20 to 28, and Week 29 to 52 between treatment groups
3. To compare the proportion of patients with mean Hb ≥10.0 g/dL, averaged over Week 20 to Week 28, and Week 29 to Week 52 between treatment groups
4. To compare safety between treatment groups
5. To evaluate the mean dose of efepoetin alfa used over the course of the study
6. To evaluate the proportion of patients requiring rescue therapy
7. To compare the Quality of Life (QoL) in patients with CKD on hemodialysis between treatment groups.
8. To evaluate immunogenicity (Anti-Drug Antibody [ADA]).

Conditions and MedDRA coding

Anemia in patients with chronic kidney disease on dialysis

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Adult males and females ≥ 18 years old.
2. 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
3. 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.
4. Hemodialysis patients with single-pool Kt/V ≥ 1.2 or urea reduction ratio ≥ 65%.
5. 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
6. 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.
7. Patients with serum ferritin ≥100 ng/mL at screening.
8. Patients with transferrin saturation (TSAT) ≥20% at screening.
9. Serum folate concentrations ≥lower limit of normal (LLN) at screening.
10. Serum total vitamin B12 concentrations ≥LLN at screening.

Exclusion criteria 25

1. 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).
2. 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).
3. Immunosuppressive therapy (tacrolimus/cyclosporine, and other than corticosteroids for a chronic condition) within 12 weeks prior to Day 1.
4. 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.
5. History of alcohol or drug abuse within the past 2 years and inability to avoid consumption of more than >3 alcoholic beverages per day.
6. Use of an investigational medication or treatment, participation in an investigational interventional study, or carryover effect of an investigational treatment expected during the study.
7. 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.
8. 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.
9. 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.
10. 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
11. Chronic congestive heart failure (New York Heart Association class III or IV).
12. 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.
13. 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.
14. 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).
15. 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.
16. 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.
17. 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.
18. Any prior functioning organ transplant or a scheduled organ transplantation, or anephric state (one or both kidneys).
19. Planned elective surgery that could lead to significant blood loss during the study period.
20. Hypoalbuminemia (Serum albumin <2.5 g/dL) at Screening Visit.
21. Androgen, deferoxamine, deferiprone, or deferasirox therapy within 12 weeks prior to Day 1.
22. Life expectancy of <12 months.
23. Cognitive or psychiatric condition rendering the patient unable to be cooperative with and complete study requirements.
24. Hypersensitivity to any one of the investigational drugs or its excipients.
25. Patients with very limited functional capacity for which a target Hb value of 12 g/dL may have a lower benefit/risk ratio.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 8

1. Mean change from Baseline in Hb averaged over Week 20 to Week 28, regardless of whether the patient received rescue therapy.
2. Mean change from Baseline in Hb level averaged over the maintenance period, regardless of whether the patient received rescue therapy
3. 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.
4. 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.
5. Proportion of patients requiring rescue therapy during study treatment and time to rescue therapy from date of first dose of study treatment.
6. Proportion of patients receiving rescue therapy over Week 20 to Week 28, and over the maintenance period.
7. Mean dose of the IP over Week 20 to Week 28, and over the maintenance period.
8. Mean change in QoL from Day 1 (V2) over time assessed through the 36-Item Health Survey 1.0 Questionnaire (Rand SF-36).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genexine Inc.

Sponsor organisation

Genexine Inc.

Address

700 Daewangpangyo-Ro, Bundang Bundang

City

Seongnam

Postcode

13488

Country

Korea, Republic of

Scientific contact point

Organisation

Genexine Inc.

Contact name

TaeKyung Seong

Public contact point

Organisation

Genexine Inc.

Contact name

TaeKyung Seong

Third parties 3

Locations

5 EU/EEA countries · 36 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications