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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Pharmalink AB
ClinicalTrials.gov Identifier:
NCT01738035
First received: July 25, 2012
Last updated: January 8, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Primary IgA Nephropathy
Drug: NEFECON
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Pharmalink AB:

Primary Outcome Measures:
  • Change from baseline in urine protein creatinine ratio [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in urine albumin creatinine ratio [ Time Frame: 9 months ] [ Designated as safety issue: No ]
  • Change from baseline in 24 hour albuminuria [ Time Frame: 9 months ] [ Designated as safety issue: No ]
  • Change from baseline in estimated GFR [ Time Frame: 9 months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Change from baseline in urine protein creatinine ratio [ Time Frame: 3-12 months ] [ Designated as safety issue: No ]
  • Change in urine albumin creatinine ratio [ Time Frame: 3-12 months ] [ Designated as safety issue: No ]
  • Change from baseline in 24 hour albuminuria [ Time Frame: 3-12 months ] [ Designated as safety issue: No ]
  • Change from baseline in estimated GFR [ Time Frame: 3-12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 90
Study Start Date: December 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01738035

  Show 58 Study Locations
Sponsors and Collaborators
Pharmalink 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
  More Information

No publications provided

Responsible Party: Pharmalink AB
ClinicalTrials.gov Identifier: NCT01738035     History of Changes
Other Study ID Numbers: Nef-202, 2012-001923-11
Study First Received: July 25, 2012
Last Updated: January 8, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Pharmalink AB:
IgA nephropathy

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Glomerulonephritis, IGA
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Glomerulonephritis
Nephritis
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 18, 2014