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

Primary IgA Nephropathy Clinical Trial

— NEFIGAN  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01738035
• Other study ID #: Nef-202
• Secondary ID: 2012-001923-11
• Status: Completed
• Phase: Phase 2
• First received: July 25, 2012
• Last updated: September 23, 2015
• Start date: December 2012
• Est. completion date: September 2015

Study information

• Verified date: September 2015
• Source: Pharmalink AB
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyFinland: Finnish Medicines AgencyGermany: Federal Institute for Drugs and Medical DevicesItaly: The Italian Medicines AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Spain: Spanish Agency of MedicinesSweden: Medical Products AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: September 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

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

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• Kidney Diseases
• Kidney Failure, Chronic
• Primary IgA Nephropathy

Intervention

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:
• 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.

Locations

Country	Name	City	State
Belgium	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
Czech Republic	University Hospital	Olomouc
Czech Republic	Charles University & General University Hospital	Prague
Czech Republic	Institut klinické a experimentální medicíny	Prague
Denmark	Rigshospitalet	Copenhagen
Denmark	Herlev Hospital	Herlev
Denmark	Odense University Hospital	Odense
Finland	Helsinki University Central Hospital	Helsinki
Finland	Tampere University Hospital	Tampere
Finland	Turku University Central Hospital	Turku
Germany	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
Italy	Policlinico di Bari	Bari
Italy	Azienda Ospedaliera G. Brotzu	Cagliari
Italy	Ospedale A Manzoni	Lecco
Italy	Bassini Hospital	Milano
Italy	Ospedale S. G. Bosco	Torino
Italy	Belcolle Hospital	Viterbo
Netherlands	University Medical Center	Leiden
Spain	Fundación Puigver	Barcellona
Spain	Hospital Universitario Vall d'Hebron	Barcellona
Spain	12 de Octubre Hospital	Madrid
Spain	Fundación Jimenez Diaz Hospital	Madrid
Spain	Hospital Universitario Gregorio Marañon	Madrid
Sweden	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
United Kingdom	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

Sponsors (1)

Lead Sponsor	Collaborator
Pharmalink AB

Countries where clinical trial is conducted

Belgium,  Czech Republic,  Denmark,  Finland,  Germany,  Italy,  Netherlands,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from baseline in urine protein creatinine ratio		3-12 months	No
Other	Change in urine albumin creatinine ratio		3-12 months	No
Other	Change from baseline in 24 hour albuminuria		3-12 months	No
Other	Change from baseline in estimated GFR		3-12 months	No
Primary	Change from baseline in urine protein creatinine ratio		9 months	No
Secondary	Change from baseline in urine albumin creatinine ratio		9 months	No
Secondary	Change from baseline in 24 hour albuminuria		9 months	No
Secondary	Change from baseline in estimated GFR		9 months	No