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

Sponsor
Calliditas Therapeutics AB (Industry)
Overall Status
Completed
CT.gov ID
NCT01738035
Collaborator
(none)
150
Enrollment
58
Locations
3
Arms
33
Duration (Months)
2.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
150 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicentre, Interventional Treatment, Randomized, Double-Blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Two Different Doses of Nefecon in Primary IgA Nephropathy Patients at Risk of End-stage Renal Disease
Study Start Date :
Dec 1, 2012
Actual Primary Completion Date :
Jun 1, 2015
Actual Study Completion Date :
Sep 1, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: NEFECON 8 mg/day

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

Drug: 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.
Other Names:
  • Budesonide modified-released capsules (4 mg/capsule)

    		•
    Experimental: NEFECON 16 mg/day

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

    Drug: 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.
    Other Names:
  • Budesonide modified-released capsules (4 mg/capsule)

    		•
    Placebo Comparator: Placebo

    Placebo (4 placebo capsules daily) for 9 months

    Other: 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.

    Outcome Measures

    Primary Outcome Measures

    1. Change from baseline in urine protein creatinine ratio [9 months]

    Secondary Outcome Measures

    1. Change from baseline in urine albumin creatinine ratio [9 months]

    2. Change from baseline in 24 hour albuminuria [9 months]

    3. Change from baseline in estimated GFR [9 months]

    Other Outcome Measures

    1. Change from baseline in urine protein creatinine ratio [3-12 months]

    2. Change in urine albumin creatinine ratio [3-12 months]

    3. Change from baseline in 24 hour albuminuria [3-12 months]

    4. Change from baseline in estimated GFR [3-12 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Screening 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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University Hospital of Antwerp Antwerp Belgium
    2 Imelda Hospital Bonheiden Belgium
    3 Ghent University Hospital Ghent Belgium
    4 University Hospitals Leuven Leuven Belgium
    5 Heilig Hartziekenhuis Roeselare-Menen Roeselare Belgium
    6 University Hospital Olomouc Czech Republic
    7 Charles University & General University Hospital Prague Czech Republic
    8 Institut klinické a experimentální medicíny Prague Czech Republic
    9 Rigshospitalet Copenhagen Denmark
    10 Herlev Hospital Herlev Denmark
    11 Odense University Hospital Odense Denmark
    12 Helsinki University Central Hospital Helsinki Finland
    13 Tampere University Hospital Tampere Finland
    14 Turku University Central Hospital Turku Finland
    15 RWTH Aachen Aachen Germany
    16 Klinikum Augsburg Augsburg Germany
    17 Charité Hospital Berlin Germany
    18 Charité-Virchow Clinic Berlin Germany
    19 Vivantes Klinikum im Friedrichshain Berlin Germany
    20 Klinikum-Bremen-Mitte Bremen Germany
    21 University Hospital Carl Gustav Carus Dresden Germany
    22 Studienzentrum Karlstrasse Düsseldorf Germany
    23 Universitätsklinikum Erlangen Erlangen Germany
    24 Universitätsmedizin Göttingen Göttingen Germany
    25 University Hospital Heidelberg Germany
    26 University of Jena Jena Germany
    27 Universitätsklinikum Magdeburg Magdeburg Germany
    28 Universität München Munich Germany
    29 Universitätsklinikum Münster Münster Germany
    30 Universitätsklinikum Regensburg Regensburg Germany
    31 Deutsche Klinik für Diagnostik Wiesbaden Germany
    32 Würzburg University Hospital Würzburg Germany
    33 Policlinico di Bari Bari Italy
    34 Azienda Ospedaliera G. Brotzu Cagliari Italy
    35 Ospedale A Manzoni Lecco Italy
    36 Bassini Hospital Milano Italy
    37 Ospedale S. G. Bosco Torino Italy
    38 Belcolle Hospital Viterbo Italy
    39 University Medical Center Leiden Netherlands
    40 Fundación Puigver Barcellona Spain
    41 Hospital Universitario Vall d'Hebron Barcellona Spain
    42 12 de Octubre Hospital Madrid Spain
    43 Fundación Jimenez Diaz Hospital Madrid Spain
    44 Hospital Universitario Gregorio Marañon Madrid Spain
    45 Central sjukhuset Karlstad Sweden
    46 Karlstad Central Hospital Karlstad Sweden
    47 University Hospital Linköping Sweden
    48 Danderyds Hospital Stockholm Sweden
    49 Karolinska University Hospital Stockholm Sweden
    50 Uppsala University Hospital Uppsala Sweden
    51 Belfast City Hospital Belfast United Kingdom
    52 Ulster Hospital Belfast United Kingdom
    53 Royal Derby Hospital Derby United Kingdom
    54 Edinburgh Royal Infirmary Edinburgh United Kingdom
    55 Western Infirmary Glasgow United Kingdom
    56 The Leeds Teaching Hospitals NHS Trust Leeds United Kingdom
    57 Leicester General Hospital Leicester United Kingdom
    58 James Cook University Hospital Middlesbrough United Kingdom

    Sponsors and Collaborators

    • Calliditas Therapeutics AB

    Investigators

    • Principal Investigator: Bengt Fellström, MD, PhD, Professor of Medicine Department of Medical Sciences, Renal Medicine Uppsala University Hospital, Sweden
    • Study Director: Alex Mercer, PhD, Pharmalink AB, Stockholm, Sweden

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Calliditas Therapeutics AB
    ClinicalTrials.gov Identifier:
    NCT01738035
    Other Study ID Numbers:
    • Nef-202
    • 2012-001923-11
    First Posted:
    Nov 30, 2012
    Last Update Posted:
    Sep 24, 2015
    Last Verified:
    Sep 1, 2015
    Keywords provided by Calliditas Therapeutics AB
    IgA nephropathy
    Additional relevant MeSH terms:
    Kidney Diseases
    Kidney Failure, Chronic
    Glomerulonephritis, IGA
    Budesonide

    Study Results

    No Results Posted as of Sep 24, 2015