A study in which the safety and efficacy of Nefecon is compared with placebo in patients with primary IgA Nephropathy.

• Register: EUCTR
• Last refreshed on: 23 October 2023
• Main ID: EUCTR2017-004902-16-ES
• Date of registration: 02/03/2018
• Prospective Registration: Yes
• Primary sponsor: Calliditas Therapeutics AB
• Public title: A study in which the safety and efficacy of Nefecon is compared with placebo in patients with primary IgA Nephropathy.
• Scientific title: A Randomized, Double-Blind, Placebo Controlled Study to Evaluate Efficacy and Safety of Nefecon in Patients with Primary IgA Nephropathy at Risk of Progressing to End-Stage Renal Disease (NefIgArd).
• Date of first enrolment: 09/04/2018
• Target sample size: 450
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-004902-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belarus, Belgium, Canada, Czech Republic, Finland, France, Germany, Greece, Italy, Korea, Republic of, Poland, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Operations
• Affiliation: Calliditas Therapeutics AB

• Name: Clinical Operations
• Affiliation: Calliditas Therapeutics AB

Key inclusion & exclusion criteria

Inclusion criteria:
Patients must meet all of the following inclusion criteria at screening to be eligible for admission into the study:
1. Female or male patients 18 years of age;
2. Diagnosed IgAN with biopsy verification within the past 5 years;
3. On a stable dose of RAS inhibitor therapy (ACEIs and/or ARBs) at the maximum allowed dose or MTD according to the 2012 KDIGO guidelines for the 3 months prior to screening. In this instance, a stable dose is defined as doses within 25% of the dose at screening. Patients that are on a stable dose of RAS inhibitor therapy (ACEIs and/or ARBs) that is below the maximum allowed dose or MTD according to the 2012 KDIGO guidelines will be permitted into the study if an attempt to reach the maximum allowed dose or MTD was previously performed; and
4. Willing and able to provide written informed consent at screening.
In addition, patients must meet the following inclusion criteria before randomization into the study:
5. Proteinuria based on 2 consecutive measurements (based on 24-hour urine sampling) after informed consent, separated by at least 2 weeks and calculated by the central laboratory. Both samples must show either of the following:
- Proteinuria ?1 g per day, or
- UPCR ?0.8 g/gram; and
6. eGFR ?45 mL/min per 1.73 m2 and 90 mL/min per 1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, confirmed by the central laboratory.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 410
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion criteria:
Patients who meet any of the following exclusion criteria at screening will not be eligible for admission into the study:
1. Systemic diseases that may cause mesangial IgA deposition including, but not limited to, Henoch Schönlein purpura, systemic lupus erythematosus, dermatitis herpetiformis, and ankylosing spondylitis;
2. Patients who have undergone a kidney transplant;
3. Patients with acute or chronic infectious disease including hepatitis, tuberculosis, human immunodeficiency virus (HIV), and chronic urinary tract infections;
4. Patients with liver cirrhosis, as assessed by the Investigator;
5. Patients with a diagnosis of type 1 or type 2 diabetes mellitus which is poorly controlled (defined as hemoglobin A1c [HbA1c] 8% [64 mmol/mol]);
6. Patients with history of unstable angina, class III or IV congestive heart failure, and/or clinically significant arrhythmia, as judged by the Investigator;
7. Patients with unacceptable blood pressure control defined as a blood pressure consistently above national guidelines for proteinuric renal disease, as assessed by the Investigator; patients with 140 mmHg systolic blood pressure or 90 mmHg diastolic blood pressure are not eligible;
8. Patients with diagnosed malignancy within the past 5 years, except for treated basal cell carcinoma of the skin, curatively resected squamous cell carcinoma of the skin, colon polyps, or cervical carcinoma in situ;
9. Patients with known osteoporosis in medium- or high-risk category according to the 2010 American College of Rheumatology recommendations;
10. Patients with known glaucoma, known cataract(s), and/or history of cataract surgery, unless the surgery was performed on both eyes;
11. Gastrointestinal disorders (eg, peptic ulcer disease, inflammatory bowel disease, and chronic diarrhea) that may interfere with the effects of the study drug;
12. Patients with hypersensitivity to budesonide or any component of the study drug formulation;
13. Patients with previous severe adverse reactions to steroids, at the discretion of the Investigator, including psychotic symptoms;
14. Patients who have been treated with immunosuppressive medications, other than GCSs, within the past 2 years. See Appendix F for more information on immunosuppressive medications;
15. Patients who have been treated with any systemic GCSs within the past 3 months;
16. Patients who have been treated with any systemic GCSs within the past 2 years except for a maximum of 3 periods of 2 weeks with the equivalent of 0.5 mg/kg prednisolone or less, for non-IgAN indications;
17. Patients taking potent inhibitors of cytochrome P450 (CYP) 3A4;
18. Current or prior (within the past 2 years) alcohol or drug abuse;
19. Intake of an investigational drug within 30 days and at least 5 half-lives;
20. Patients unwilling or unable to meet the requirements of the protocol;
21. Other medical or social reasons for exclusion at the discretion of the Investigator;
22. Life expectancy 5 years;
23. Females who are pregnant, breastfeeding, or unwilling to use highly-effective contraception during the Treatment Period and the 3-month Follow-up Period in Part A of the study (contraception only required for women of childbearing potential [WOCBP]);
- Highly-effective methods of contraception are defined as those that achieve a low failure rate (1% per year) when used consistently and correctly. Such methods include the use of combined (estrogen and progesterone) hormonal contraceptives (oral, intravaginal, or

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Primary IgA nephropathy patients at risk of developing end stage renal disease
MedDRA version: 20.0 Level: LLT Classification code 10069341 Term: Berger's disease System Organ Class: 100000004857

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Nefecon
Product Code: Nefecon
Pharmaceutical Form: Modified-release capsule, hard
INN or Proposed INN: BUDESONIDE
CAS Number: 51333-22-3
Other descriptive name: Nefecon
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
Pharmaceutical form of the placebo: Modified-release capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: A formal interim analysis of the full study will be performed when 50 clinical events, defined as occurrence of a 30% reduction from baseline in eGFR, have occurred.

Main Objective: Part A:
The primary objective of Part A is to assess the effect of Nefecon 16 mg treatment on urine protein to creatinine ratio (UPCR) over 9 months compared to placebo.
Part B:
The primary objective of Part B is to assess the effect of the Nefecon treatment given in Part A on long-term clinical consequences of any proteinuria reduction as measured by the time to 30% reduction in estimated glomerular filtration rate (eGFR) compared to placebo.

Secondary Objective: Part A:
The secondary objectives of Part A are to evaluate additional aspects of renal function, and safety and tolerability of Nefecon 16 mg treatment over 9 months compared to placebo.
Part B:
The secondary objectives of Part B are to assess the long-term effects of the Nefecon treatment given in Part A on different aspects of renal function and long-term safety compared to placebo.

Primary end point(s): The primary efficacy endpoint for the final analysis is defined as the time from the first dose of study drug until the first occurrence of a 30% reduction from baseline in eGFR (CKD-EPI). The 30% reduction must be confirmed by a second value obtained within 30 days to 100 days of the original.

Secondary Outcome(s)

Secondary end point(s): • Time from the first dose of study drug until the first occurrence of the initiation of maintenance dialysis for at least 1 month, kidney transplantation, or kidney failure defined as a sustained eGFR <15 mL/min/1.73 m2, or death due to kidney failure;
• Ratio of UPCR, UACR, and eGFR (CKD-EPI) compared to baseline averaged over time points between 12 and 24 months inclusive following the first dose of study drug;
• Time to 40% reduction from baseline in eGFR (CKD-EPI) confirmed by a second value obtained within 30 days to 100 days;
• Time to 50% reduction from baseline in eGFR (CKD-EPI) confirmed by a second value obtained within 30 days to 100 days;
• Proportion of patients with a total proteinuria level 1 g per 24 hours or UPCR 0.8 g/gram at 12, 18, and 24 months following the first dose of study drug, and at the last study visit;
• Proportion of patients with proteinuria ?1 g per 24 hours or UPCR 0.8 g/gram in at least 2 of the following time points: 12, 18, and 24 months following the first dose of study drug;
• Proportion of patients without microhematuria at 12, 18, and 24 months following the first dose of study drug, and at the last study visit;
• Proportion of patients without microhematuria in at least 2 of the following time points: 12, 18, and 24 months following the first dose of study drug;
• Proportion of patients receiving rescue treatment; and
• SF-36 quality of life assessment

Timepoint(s) of evaluation of this end point: - Ratio of UPCR, UACR, and eGFR (CKD-EPI): between 12 and 24 months
- 40% reduction in eGFR (CKD-EPI): a second value obtained within 30 days to 100 days;
- 50% reduction in eGFR (CKD-EPI): a second value obtained within 30 days to 100 days;
- Proportion of patients with a total proteinuria level 1 g per 24 hours or UPCR 0.8 g/gram at 12, 18, and 24 months following the first dose of study drug, and at the last study visit
- Patients without microhematuria:12,18, and 24 months and at the last study visit;

Secondary ID(s)

2017-004902-16-CZ

Nef-301

Source(s) of Monetary Support

Calliditas Therapeutics AB

Ethics review

Status: Approved
Approval date: 22/03/2018
Contact: