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

NCT ID: NCT01738035

Last Updated: 2015-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2015-09-30

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.

Conditions

Primary IgA Nephropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

NEFECON 8 mg/day

NEFECON 8 mg/day (2 active + 2 placebo capsules daily) for 9 months

Group Type: EXPERIMENTAL

NEFECON

Intervention Type: DRUG

All patients will receive a maximum recommended daily dose of an ACEI and/or ARB (or maximum tolerated dose not exceeding the maximum recommended daily dose) for the duration of the treatment and follow-up phases.

NEFECON 16 mg/day

NEFECON 16 mg/day (4 active capsules daily) for 9 months

Group Type: EXPERIMENTAL

NEFECON

Intervention Type: DRUG

All patients will receive a maximum recommended daily dose of an ACEI and/or ARB (or maximum tolerated dose not exceeding the maximum recommended daily dose) for the duration of the treatment and follow-up phases.

Placebo

Placebo (4 placebo capsules daily) for 9 months

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

All patients will receive a maximum recommended daily dose of an ACEI and/or ARB (or maximum tolerated dose not exceeding the maximum recommended daily dose) for the duration of the treatment and follow-up phases.

Interventions

NEFECON

All patients will receive a maximum recommended daily dose of an ACEI and/or ARB (or maximum tolerated dose not exceeding the maximum recommended daily dose) for the duration of the treatment and follow-up phases.

Intervention Type: DRUG

Placebo

All patients will receive a maximum recommended daily dose of an ACEI and/or ARB (or maximum tolerated dose not exceeding the maximum recommended daily dose) for the duration of the treatment and follow-up phases.

Intervention Type: OTHER

Other Intervention Names

Budesonide modified-released capsules (4 mg/capsule)

Eligibility Criteria

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

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

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)

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Calliditas Therapeutics AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bengt Fellström, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Professor of Medicine Department of Medical Sciences, Renal Medicine Uppsala University Hospital, Sweden

Alex Mercer, PhD

Role: STUDY_DIRECTOR

Pharmalink AB, Stockholm, Sweden

Locations

University Hospital of Antwerp

Antwerp, , Belgium

Imelda Hospital

Bonheiden, , Belgium

Ghent University Hospital

Ghent, , Belgium

University Hospitals Leuven

Leuven, , Belgium

Heilig Hartziekenhuis Roeselare-Menen

Roeselare, , Belgium

University Hospital

Olomouc, , Czechia

Charles University & General University Hospital

Prague, , Czechia

Institut klinické a experimentální medicíny

Prague, , Czechia

Rigshospitalet

Copenhagen, , Denmark

Herlev Hospital

Herlev, , Denmark

Odense University Hospital

Odense, , Denmark

Helsinki University Central Hospital

Helsinki, , Finland

Tampere University Hospital

Tampere, , Finland

Turku University Central Hospital

Turku, , Finland

RWTH Aachen

Aachen, , Germany

Klinikum Augsburg

Augsburg, , Germany

Charité Hospital

Berlin, , Germany

Charité-Virchow Clinic

Berlin, , Germany

Vivantes Klinikum im Friedrichshain

Berlin, , Germany

Klinikum-Bremen-Mitte

Bremen, , Germany

University Hospital Carl Gustav Carus

Dresden, , Germany

Studienzentrum Karlstrasse

Düsseldorf, , Germany

Universitätsklinikum Erlangen

Erlangen, , Germany

Universitätsmedizin Göttingen

Göttingen, , Germany

University Hospital

Heidelberg, , Germany

University of Jena

Jena, , Germany

Universitätsklinikum Magdeburg

Magdeburg, , Germany

Universität München

Munich, , Germany

Universitätsklinikum Münster

Münster, , Germany

Universitätsklinikum Regensburg

Regensburg, , Germany

Deutsche Klinik für Diagnostik

Wiesbaden, , Germany

Würzburg University Hospital

Würzburg, , Germany

Policlinico di Bari

Bari, , Italy

Azienda Ospedaliera G. Brotzu

Cagliari, , Italy

Ospedale A Manzoni

Lecco, , Italy

Bassini Hospital

Milan, , Italy

Ospedale S. G. Bosco

Torino, , Italy

Belcolle Hospital

Viterbo, , Italy

University Medical Center

Leiden, , Netherlands

Fundación Puigver

Barcelona, , Spain

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

12 de Octubre Hospital

Madrid, , Spain

Fundación Jimenez Diaz Hospital

Madrid, , Spain

Hospital Universitario Gregorio Marañon

Madrid, , Spain

Central sjukhuset

Karlstad, , Sweden

Karlstad Central Hospital

Karlstad, , Sweden

University Hospital

Linköping, , Sweden

Danderyds Hospital

Stockholm, , Sweden

Karolinska University Hospital

Stockholm, , Sweden

Uppsala University Hospital

Uppsala, , Sweden

Belfast City Hospital

Belfast, , United Kingdom

Ulster Hospital

Belfast, , United Kingdom

Royal Derby Hospital

Derby, , United Kingdom

Edinburgh Royal Infirmary

Edinburgh, , United Kingdom

Western Infirmary

Glasgow, , United Kingdom

The Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

Leicester General Hospital

Leicester, , United Kingdom

James Cook University Hospital

Middlesbrough, , United Kingdom

Countries

Belgium; Czechia; Denmark; Finland; Germany; Italy; Netherlands; Spain; Sweden; United Kingdom

References

Fellstrom BC, Barratt J, Cook H, Coppo R, Feehally J, de Fijter JW, Floege J, Hetzel G, Jardine AG, Locatelli F, Maes BD, Mercer A, Ortiz F, Praga M, Sorensen SS, Tesar V, Del Vecchio L; NEFIGAN Trial Investigators. Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial. Lancet. 2017 May 27;389(10084):2117-2127. doi: 10.1016/S0140-6736(17)30550-0. Epub 2017 Mar 28.

Reference Type: DERIVED

PMID: 28363480 (View on PubMed)

Yeo SC, Liew A, Barratt J. Emerging therapies in immunoglobulin A nephropathy. Nephrology (Carlton). 2015 Nov;20(11):788-800. doi: 10.1111/nep.12527.

Reference Type: DERIVED

PMID: 26032537 (View on PubMed)

Other Identifiers

2012-001923-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Nef-202

Identifier Type: -

Identifier Source: org_study_id