Primary IgA Nephropathy
Conditions
Keywords
IgA nephropathy
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.
Interventions
DRUGNEFECON
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.
OTHERPlacebo
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.
Sponsors
Calliditas Therapeutics AB
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in urine protein creatinine ratio | 9 months |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
Other
| Measure | Time frame |
|---|---|
| Change from baseline in urine protein creatinine ratio | 3-12 months |
| Change in urine albumin creatinine ratio | 3-12 months |
| Change from baseline in 24 hour albuminuria | 3-12 months |
| Change from baseline in estimated GFR | 3-12 months |
Countries
Belgium, Czechia, Denmark, Finland, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom
Outcome results
None listed