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: 5 April 2021
• Main ID: EUCTR2017-004902-16-IT
• Date of registration: 20/01/2021
• Prospective Registration: No
• 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). - A study in which the safety and efficacy of Nefecon is compared with placebo in patients with primar
• Date of first enrolment: 16/11/2018
• Target sample size: 360
• Recruitment status: Authorised-recruitment may be ongoing or finished
• 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, China, Czech Republic, Czechia, Finland, France, Germany, Greece, Italy, Korea, Republic of, Poland, Spain, Sweden, Taiwan, Turkey, United Kingdom

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 10 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 randomization (see Appendix D). In this instance, a stable dose is defined as doses within 25% of the dose at randomization. Patients on a stable dose of RAS inhibitor therapy (ACEIs and/or ARBs) 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 has been performed21 or if
such attempt is deemed unsafe for the patient by the Investigator; and Note: It is recommended that patients achieve a target systolic blood pressure <125 mmHg and target diastolic blood pressure <75 mmHg according to the 2012 KDIGO guidelines.
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 (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:
o Proteinuria =1 g per day (=1000 mg per day) in 2 consecutive
measurements, or
o UPCR =0.8 g/gram (=90 mg/mmol) in 2 consecutive measurements; and
6. eGFR >=35 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 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 328
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32

Exclusion criteria:
Please refer to the protocol due to characters number limitation


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
Current Sponsor code: -
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)

Secondary Objective: Part A:
The secondary objectives of Part A are:
• To assess the effect of Nefecon 16 mg treatment on eGFR at 9 and 12 months compared to placebo, and
• 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 effects of the Nefecon 16 mg treatment given in Part A on different aspects of renal function and safety compared to placebo over 2 years.

Primary end point(s): The primary efficacy endpoint for the Part A analysis is defined as the ratio of UPCR (based on 24 hour urine collections) at 9 months following the first dose of study drug compared to baseline. The primary efficacy endpoint for the Part B analysis is an area under the curve (AUC)-based endpoint of eGFR calculated as a time-weighted average of eGFR recordings observed at each time point over 2 years. The eGFR (CKD EPI) at 2 years (which must be repeated by a second value obtained within 14 to 35 days) will be the geometric mean of the 2 assessments.

Timepoint(s) of evaluation of this end point: Data analysis will include the first 200 patients randomized. The data cut-off for the Part A analysis will occur 9.5 months after the 200th patient randomized is dosed (or, if the 200th patient randomized does not receive any study drug, 9.5 months after the 200th patient is randomized). Supportive analyses of the above endpoints will also be performed at other time points to describe the time course of effect. The Part B analysis will be performed when the 360th/last patient randomized has been followed for 25 months after the first dose (or, if the 360th/last patient randomized does not receive any study drug, 25 months after the 360th/last patient is randomized). At the time of the Part B analysis, the Part A analysis will be repeated using all patients randomized.

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 16 mg treatment given in Part A on clinical consequences of any proteinuria reduction as measured by estimated glomerular filtration rate (eGFR) recorded over 2 years compared to placebo.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Timepoints are described within the text in section E.5.1.1

Secondary ID(s)

Nef-301

2017-004902-16-CZ

Source(s) of Monetary Support

Calliditas Therapeutics AB

Ethics review

Status: Approved
Approval date: 19/07/2018
Contact: