Study in which Efficacy and Safety of Nefecon is Evaluated in Patients With IgA Nepropathy Who Have Completed Study Nef-301

• Register: EUCTR
• Last refreshed on: 16 September 2024
• Main ID: EUCTR2020-003308-14-FR
• Date of registration: 13/10/2020
• Prospective Registration: Yes
• Primary sponsor: Calliditas Therapeutics AB
• Public title: Study in which Efficacy and Safety of Nefecon is Evaluated in Patients With IgA Nepropathy Who Have Completed Study Nef-301
• Scientific title: An Open-Label Extension (OLE) Study to Evaluate the Efficacy and Safety of Nefecon Treatment in Patients With IgA Nephropathy Who Have Completed Study Nef-301
• Date of first enrolment: 13/11/2020
• Target sample size: 250
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-003308-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• 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:
-Completed Study Nef-301, defined as Part A (9-month study drug treatment [Nefecon 16 mg/day or placebo] and 3-month follow-up) and Part B (12-month follow-up);
-Completed Visit 17b in Study Nef-301 within 3 months before Study Visit 3;
-On a stable dose of RAS inhibitor therapy (ACEIs and/or ARBs) at the maximum allowed dose or maximum tolerated dose according to the 2012 KDIGO guidelines21 (see Appendix C). A stable dose is defined as a dose within 25% of the dose at Visit 17a or 17b in Study Nef 301; and
-Proteinuria based on 2 consecutive measurements (24-hour urine sampling) after informed consent, separated by at least 2 weeks and calculated by the central laboratory. Both samples of the same parameter must show either of the following:
oProteinuria >/=1 g/day (>/=1000 mg/day) in 2 consecutive measurements; or
oUPCR >/=0.8 g/gram (?90 mg/mmol) in 2 consecutive measurements; and
-eGFR >/=30 mL/min per 1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula confirmed by the central laboratory at Study Visit 1 or Study Visit 3.

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 227
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 23

Exclusion criteria:
-Had a dose reduction to Nefecon 8 mg/day in Study Nef-301;
-Systemic diseases that may cause mesangial IgA deposition including, but not limited to, Henoch Schönlein purpura, systemic lupus erythematosus, dermatitis herpetiformis, and ankylosing spondylitis;
-Patients with nephrotic syndrome (i.e., proteinuria >3.5 g/day and with serum albumin <3.0 g/dL, with or without edema);
-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. At least 1 blood pressure measurement at either Study Visit 1 or Study Visit 3 should be within these limits (based on up to 3 measurements, measured 1 minute apart, after resting in the supine position for at least 5 minutes);
-Patients who have received rescue therapy with systemic immunosuppressants, including GCSs, during Study Nef-301;
-Patients who have been treated with any systemic GCSs within the 3 months before screening;
-Patients who have been treated with any systemic GCSs within the 12 months before screening except for a maximum of 3 periods of 2 weeks with the equivalent of 0.5 mg/kg/day prednisolone or less for non-IgAN indications;



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

Health Condition(s) or Problem(s) studied

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

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

Intervention(s)

Product Name: Nefecon
Product Code: Nefecon
Pharmaceutical Form: Modified-release capsule, hard
INN or Proposed INN: BUDESONIDE
CAS Number: 51333-22-3
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: included in E.5.1

Main Objective: •To assess the effect of 9 months of retreatment with Nefecon on urine protein to creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) in patients who completed Study Nef 301 with Nefecon treatment; and
•To assess the effect of 9 months of treatment with Nefecon on UPCR and eGFR in patients who completed Study Nef-301 with placebo treatment.

Secondary Objective: •To assess the safety and tolerability of 9 months of retreatment with Nefecon in patients who completed Study Nef-301 with Nefecon treatment;
•To assess the safety and tolerability of 9 months of treatment with Nefecon in patients who completed Study Nef-301 with placebo treatment;
•To assess the effect of 9 months of retreatment with Nefecon on additional aspects of renal function in patients who completed Study Nef-301 with Nefecon treatment; and
•To assess the effect of 9 months of treatment with Nefecon on additional aspects of renal function in patients who completed Study Nef-301 with placebo treatment.

Primary end point(s): •Ratio of eGFR at 9 months compared to baseline, calculated using the CKD-EPI formula; and
•Ratio of UPCR at 9 months compared to baseline.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: included in E.5.2

Secondary end point(s): •Ratio of urine albumin to creatinine ratio (UACR) at 9 months compared to baseline;
•Short Form 36 quality of life assessment at 12 months compared to baseline;
•Proportion of patients with microhematuria at 9 months compared to baseline;
•Proportion of patients receiving rescue treatment and time to receiving rescue treatment;
•Proportion of patients on dialysis, undergoing kidney transplantation, or with eGFR <15 mL/min per 1.73 m2; and
•Cortisol suppression at 9 and 12 months, measured as urinary cortisol excretion over 24 hours compared to baseline.

Secondary ID(s)

2020-003308-14-CZ

Nef-301OLE

Source(s) of Monetary Support

Calliditas Therapeutics AB

Ethics review

Status: Approved
Approval date: 13/11/2020
Contact: