Clinical trial NCT04541043: Efficacy and Safety in Patients With Primary IgA Nephropathy Who Have Completed Study Nef-301 (Nefigard-OLE)
Official title: An Open-Label Extension (OLE) Study to Evaluate the Efficacy and Safety of Nefecon Treatment in Patients With IgA Nephropathy Who Have Completed Study Nef-301
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary IgA Nephropathy
Lead sponsor: Calliditas Therapeutics AB
Sponsor class: INDUSTRY
First posted: 2020-09-09
Enrollment: 119
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an open label, single-arm study with active treatment
Primary purpose: TREATMENT

Brief summary: This is a Phase 3b, multicenter, open-label extension (OLE) study to evaluate the efficacy and safety of Nefecon treatment in patients with IgAN who have completed the Phase 3 Study Nef-301 and continue to be treated with a stable dose of RAS inhibitor therapy (ACEIs and/or ARBs). Patients who previously received Nefecon in Study Nef-301 will receive retreatment, whereas patients who previously received placebo in Study Nef-301 will be treatment naïve to Nefecon.

Detailed description: This is a Phase 3b, multicenter, open-label extension (OLE) study to evaluate the efficacy and safety of Nefecon treatment in patients with IgAN who have completed the Phase 3 Study Nef 301 and continue to be treated with a stable dose of RAS inhibitor therapy (ACEIs and/or ARBs). Patients who previously received Nefecon in Study Nef-301 will receive retreatment, whereas patients who previously received placebo in Study Nef-301 will be treatment naïve to Nefecon. During Study Nef-301 OLE, the patients and Investigators will remain blinded to treatment given in Study Nef-301.

During Study Nef-301 OLE, patients will receive Nefecon for a 9-month period. The dose may be reduced if clinically relevant adverse events (AEs) develop during the 9-month Treatment Period that the Investigator considers related to the study drug and that mandate dose reduction.

Patients will remain on a stable dose of RAS inhibitor therapy (ACEIs and/or ARBs) throughout the study. The patient will come for a follow-up visit at 12 months after first dose.

Eligibility criteria: Inclusion Criteria:

1. Patients that completed study Nef-301
2. On a stable dose of RAS inhibitor therapy (ACEIs and/or ARBs) at the maximum allowed dose or maximum tolerated dose according to the 2012 KDIGO guidelines
3. Willing and able to provide written informed consent.
4. UPCR equal to or more than 0.8 g/gram
5. eGFR equal to or more than 30 mL/min per 1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.

Exclusion Criteria:

1. Systemic diseases that may cause mesangial IgA deposition.
2. Patients who have undergone a kidney transplant;
3. Patients with presence of other glomerulopathies and/or nephrotic syndrome
4. Patients with acute, chronic, or latent infectious disease including hepatitis, tuberculosis (TB), human immunodeficiency virus (HIV), and chronic urinary tract infections;
5. Patients with liver cirrhosis, as assessed by the Investigator;
6. Patients with a diagnosis of type 1 or type 2 diabetes mellitus which is poorly controlled
7. Patients with history of unstable angina, class III or IV congestive heart failure, and/or clinically significant arrhythmia, as judged by the Investigator;
8. Patients with unacceptable blood pressure control defined as a blood pressure consistently above national guidelines for proteinuric renal disease, as assessed by the Investigator.
9. Patients with diagnosed malignancy within the past 5 years.

Primary outcomes:
measure: Ratio of Urine Protein to Creatine Ratio (UPCR) at 9 Months Compared to Baseline
timeFrame: 9 months
measure: Ratio of Estimated Glomerular Filtration Rate (eGFR) at 9 Months Compared to Baseline
timeFrame: 9 months
Secondary outcomes:
measure: Ratio of Urine Albumin to Creatinine Ratio (UACR) at 9 Months Compared to Baseline
timeFrame: 9 months
measure: Change From Baseline Short Form 36 (SF-36) Quality of Life Assessment at 12 Months
timeFrame: Baseline & 12 months
measure: Number of Patients With Microhematuria at 9 Months Compared to Baseline
timeFrame: 9 months
measure: Number of Patients Receiving Rescue Treatment
timeFrame: 12 months
measure: Proportion of Patients on Dialysis, Undergoing Kidney Transplantation, or With eGFR <15 mL/Min Per 1.73 m2
timeFrame: 12 months
measure: Change From Baseline Cortisol Suppression at 9 Months
timeFrame: Baseline & 9 months
measure: Change From Baseline Cortisol Suppression at 12 Months
timeFrame: Baseline & 12 months
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: 13 Investigator sites
state: California
city: Buenos Aires
country: Argentina
facility: 4 Investigator sites
city: Melbourne
country: Australia
facility: 6 Investigator sites
city: Minsk
country: Belarus
facility: 3 Investigator sites
city: Brussel
country: Belgium
facility: 4 Investigator sites
city: Québec
country: Canada
facility: 7 Investigator sites
city: Praha
country: Czechia
facility: 6 Investigator sites
city: Jyväskylä
country: Finland
facility: 2 Investigator sites
city: Saint-Priest-en-Jarez
country: France
facility: 2 Investigator sites
city: Aachen
country: Germany
facility: 5 Investigator sites
city: Athens
country: Greece
facility: 5 Investigator sites
city: Milano
country: Italy
facility: 2 Investigator sites
city: Gyeonggi-do
country: Korea, Republic of
facility: 4 Investigator sites
city: Łódź
country: Poland
facility: 2 Investigator sites
city: Barcelona
country: Spain
facility: 4 Investigator sites
city: Uppsala
country: Sweden
facility: 3 Investigator sites
city: Kayseri
country: Turkey
facility: 3 Investigator sites
city: Leicester
country: United Kingdom
facility: 6 Investigator sites
Study officials:
affiliation: Calliditas Therapeutics AB
name: Richard Philipson, MD
role: STUDY_DIRECTOR
References: