The Effect of Nefecon® in Patients With Primary IgA Nephropathy at Risk of Developing End-stage Renal Disease

Phase 2

Completed

• Conditions: Primary IgA Nephropathy
• Interventions: Drug: NEFECON; Other: Placebo

• Registration Number: NCT01738035
• Lead Sponsor: Calliditas Therapeutics AB

Brief Summary

The objective of the study is to evaluate efficacy and safety of two different doses of NEFECON in the treatment of patients with primary IgA nephropathy (IgAN) at risk of developing end-stage renal disease, under rigorous blood pressure control with an angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin II receptor I blocker (ARB).

Detailed Description

NEFECON is an add-on treatment to other medications for nephropathy symptoms and kidney function, including ACEI and/or ARBs. Rigorous blood pressure control will be achieved over a 6-month Run-in Phase in which ACEI and/or ARB will be dosed to target a blood pressure of \<130/80 mm Hg and UPCR \<0.5 g/g. Patients who complete the Run-in Phase, and despite optimized ACEI and/or ARB therapy, have a UPCR ≥0.5 g/g OR urine protein ≥0.75 g/24hr will be eligible for randomization and entry into the treatment phase of the trial. Patients will remain on their ACEI and/or ARB dosing regimen for the duration of the trial.

Patients entering the treatment phase will be administered NEFECON (8 mg/day OR 16 mg/day) OR placebo for a phase of 9 months. A 3-month follow-up phase will follow on from the treatment phase, of which the first 2 weeks will be used to taper the dose of those patients that received 16 mg/day dosing to 8 mg/day, with the placebo and 8 mg/day groups receiving placebo to retain blinding.

Study Timeline

• Study First Submitted: 2012-07-25
• Study First Submitted QC: 2012-11-29
• Study First Posted: 2012-11-30
• Study Start: 2012-12
• Primary Completion: 2015-06
• Status Verified: 2015-09
• Study Completion: 2015-09
• Last Update Submitted: 2015-09-23
• Last Update Posted: 2015-09-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1. Female or male patients ≥18 years
2. Biopsy-verified IgA nephropathy
3. Urine protein creatinine ratio ≥0.5 g/g OR urine protein ≥0.75 g/24hr
4. Estimated GFR (using the CKD-EPI formula) OR measured GFR ≥50 mL/min per 1.73 m2 OR ≥45 mL/min per 1.73m2 for patients on a maximum recommended or maximum tolerated dose of an ACEI and/or ARB
5. Willing to change antihypertensive medication regimen if applicable
6. Willing and able to give informed consent

Screening

Exclusion Criteria

1. Secondary forms of IgA nephropathy as defined by the treating physician (for example, Henoch-Schönlein purpura patients and those with associated alcoholic cirrhosis)
2. Presence of crescent formation in ≥50% of glomeruli assessed on renal biopsy
3. Kidney transplanted patients 4. Severe gastrointestinal disorders (including peptic ulcer disease and inflammatory bowel disease) which may impair drug effect, or other conditions which could modify the effect of the trial drug as judged by the Investigator
4. Patients currently treated with systemic immunosuppressive or systemic corticosteroid drugs (excluding topical or nasal steroids) or have been previously treated for more than one week within the last 24 months.
5. Patients currently treated chronically (daily dosing) with inhaled corticosteroid drugs or have previously been treated chronically for more than one month within the last 12 months
6. Patients previously treated with immunosuppressive or systemic corticosteroids for the treatment of IgA nephropathy
7. Patients unable to take oral medication or intolerant to budesonide or other corticosteroid preparations
8. Patients with known allergy or intolerance to ACEI, ARB or to any component of the trial drug formulation
9. Patients with acute or chronic infectious disease incl. hepatitis, HIV positive patients and patients with chronic urinary tract infections
10. Severe liver disease according to the discretion of the Investigator
11. Patients with Type 1 or 2 diabetes
12. Patients with uncontrolled cardiovascular disease as judged by the Investigator
13. Patients with current malignancy or history of malignancy during the last three years
14. For women only; pregnant or breast feeding or unwilling to use adequate contraception during the trial (only women of child bearing potential)

Randomization Inclusion Criteria:

1. Completion of the Run-in Phase
2. Urine protein creatinine ratio ≥0.5 g/g OR urine protein ≥0.75 g/24hr
3. eGFR ≥45 mL/min per 1.73 m2 using CKD-EPI formula OR measured GFR ≥45 mL/min per 1.73 m2

Randomization Exclusion Criteria:

1. Unacceptable blood pressure defined as a systolic value >160 mm Hg or diastolic >100 mm Hg
2. eGFR (CKD-EPI) loss >30% over the entire duration of the Run-in Phase
3. For women only; pregnant or breast feeding or unwilling to use adequate contraception during the trial (only women of child bearing potential)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NEFECON 8 mg/day	NEFECON	NEFECON 8 mg/day (2 active + 2 placebo capsules daily) for 9 months
NEFECON 16 mg/day	NEFECON	NEFECON 16 mg/day (4 active capsules daily) for 9 months
Placebo	Placebo	Placebo (4 placebo capsules daily) for 9 months

Primary Outcome Measures

Name	Time	Method
Change from baseline in urine protein creatinine ratio	9 months

Secondary Outcome Measures

Name	Time	Method
Change from baseline in urine albumin creatinine ratio	9 months
Change from baseline in 24 hour albuminuria	9 months
Change from baseline in estimated GFR	9 months

Trial Locations

Locations (56)

University Hospital of Antwerp; 🇧🇪 Antwerp, Belgium

Charles University & General University Hospital; 🇨🇿 Prague, Czech Republic

Institut klinické a experimentální medicíny; 🇨🇿 Prague, Czech Republic

Ghent University Hospital; 🇧🇪 Ghent, Belgium

Imelda Hospital; 🇧🇪 Bonheiden, Belgium

12 de Octubre Hospital; 🇪🇸 Madrid, Spain

Central sjukhuset; 🇸🇪 Karlstad, Sweden

Bassini Hospital; 🇮🇹 Milano, Italy

University Hospitals Leuven; 🇧🇪 Leuven, Belgium

Heilig Hartziekenhuis Roeselare-Menen; 🇧🇪 Roeselare, Belgium

The Leeds Teaching Hospitals NHS Trust; 🇬🇧 Leeds, United Kingdom

Ulster Hospital; 🇬🇧 Belfast, United Kingdom

Würzburg University Hospital; 🇩🇪 Würzburg, Germany

Hospital Universitario Vall d'Hebron; 🇪🇸 Barcellona, Spain

University of Jena; 🇩🇪 Jena, Germany

Universitätsklinikum Magdeburg; 🇩🇪 Magdeburg, Germany

Karlstad Central Hospital; 🇸🇪 Karlstad, Sweden

Uppsala University Hospital; 🇸🇪 Uppsala, Sweden

Ospedale A Manzoni; 🇮🇹 Lecco, Italy

Ospedale S. G. Bosco; 🇮🇹 Torino, Italy

Vivantes Klinikum im Friedrichshain; 🇩🇪 Berlin, Germany

University Medical Center; 🇳🇱 Leiden, Netherlands

Universitätsklinikum Münster; 🇩🇪 Münster, Germany

Universitätsklinikum Regensburg; 🇩🇪 Regensburg, Germany

Fundación Jimenez Diaz Hospital; 🇪🇸 Madrid, Spain

Karolinska University Hospital; 🇸🇪 Stockholm, Sweden

Belcolle Hospital; 🇮🇹 Viterbo, Italy

Belfast City Hospital; 🇬🇧 Belfast, United Kingdom

Studienzentrum Karlstrasse; 🇩🇪 Düsseldorf, Germany

Deutsche Klinik für Diagnostik; 🇩🇪 Wiesbaden, Germany

Policlinico di Bari; 🇮🇹 Bari, Italy

Azienda Ospedaliera G. Brotzu; 🇮🇹 Cagliari, Italy

Hospital Universitario Gregorio Marañon; 🇪🇸 Madrid, Spain

Leicester General Hospital; 🇬🇧 Leicester, United Kingdom

James Cook University Hospital; 🇬🇧 Middlesbrough, United Kingdom

Universitätsmedizin Göttingen; 🇩🇪 Göttingen, Germany

Fundación Puigver; 🇪🇸 Barcellona, Spain

University Hospital; 🇸🇪 Linköping, Sweden

Turku University Central Hospital; 🇫🇮 Turku, Finland

Herlev Hospital; 🇩🇰 Herlev, Denmark

Odense University Hospital; 🇩🇰 Odense, Denmark

Helsinki University Central Hospital; 🇫🇮 Helsinki, Finland

Tampere University Hospital; 🇫🇮 Tampere, Finland

Klinikum Augsburg; 🇩🇪 Augsburg, Germany

University Hospital Carl Gustav Carus; 🇩🇪 Dresden, Germany

Danderyds Hospital; 🇸🇪 Stockholm, Sweden

Royal Derby Hospital; 🇬🇧 Derby, United Kingdom

Edinburgh Royal Infirmary; 🇬🇧 Edinburgh, United Kingdom

Western Infirmary; 🇬🇧 Glasgow, United Kingdom

RWTH Aachen; 🇩🇪 Aachen, Germany

Charité Hospital; 🇩🇪 Berlin, Germany

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Klinikum-Bremen-Mitte; 🇩🇪 Bremen, Germany

Charité-Virchow Clinic; 🇩🇪 Berlin, Germany

Universität München; 🇩🇪 Munich, Germany

Universitätsklinikum Erlangen; 🇩🇪 Erlangen, Germany