Efficacy and Safety in Patients With Primary IgA Nephropathy Who Have Completed Study Nef-301 (Nefigard-OLE) (Nefigard-OLE)

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

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.

Study Overview

• Status: Completed
• Conditions: Primary IgA Nephropathy
• Intervention / Treatment: Drug: Nefecon 16mg daily

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.

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
    • 4 Investigator sites
• Australia
  • Melbourne, Australia
    • 6 Investigator sites
• Belarus
  • Minsk, Belarus
    • 3 Investigator sites
• Belgium
  • Brussel, Belgium
    • 4 Investigator sites
• Canada
  • Québec, Canada
    • 7 Investigator sites
• Czechia
  • Praha, Czechia
    • 6 Investigator sites
• Finland
  • Jyväskylä, Finland
    • 2 Investigator sites
• France
  • Saint-Priest-en-Jarez, France
    • 2 Investigator sites
• Germany
  • Aachen, Germany
    • 5 Investigator sites
• Greece
  • Athens, Greece
    • 5 Investigator sites
• Italy
  • Milano, Italy
    • 2 Investigator sites
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of
    • 4 Investigator sites
• Poland
  • Łódź, Poland
    • 2 Investigator sites
• Spain
  • Barcelona, Spain
    • 4 Investigator sites
• Sweden
  • Uppsala, Sweden
    • 3 Investigator sites
• Turkey
  • Kayseri, Turkey
    • 3 Investigator sites
• United Kingdom
  • Leicester, United Kingdom
    • 6 Investigator sites
• United States
  • California
    • Palo Alto, California, United States, 94304
      • 13 Investigator sites

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Nefecon treatment; Nefecon 16 mg once daily by mouth for 9 months	Drug: Nefecon 16mg daily; All study patients received Nefecon 16 mg daily for 9 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of Urine Protein to Creatine Ratio (UPCR) at 9 Months Compared to Baseline	The outcome is measured as UPCR based on 24 hour urine collections at 9 months following the first dose of Nefecon compared to baseline Ratio being: UPCR at 9 months in g/gram divided with UPCR at Baseline in g/gram	9 months
Ratio of Estimated Glomerular Filtration Rate (eGFR) at 9 Months Compared to Baseline	The outcome is measured as ratio of eGFR in mL/min/1.73 m2 (calculated using the CKD-EPI formula) at 9 months following the first dose of Nefecon compared to baseline. I.e. eGFR at 9 months divided by eGFR at Baseline.	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of Urine Albumin to Creatinine Ratio (UACR) at 9 Months Compared to Baseline	Ratio of urine albumin to creatinine ratio (UACR) measured by 24h urine sampling at 9 months compared to baseline. I.e. UACR at 9 months divided by eGFR at Baseline.	9 months
Number of Patients With Microhematuria at 9 Months Compared to Baseline		9 months
Number of Patients Receiving Rescue Treatment	Systemic immunosuppressive drugs (including glucocorticoids in some situations ), dialysis, and renal transplantation are considered as rescue medications in this study.	12 months
Proportion of Patients on Dialysis, Undergoing Kidney Transplantation, or With eGFR <15 mL/Min Per 1.73 m2	Looking at number of patients with end stage kidney disease defined as being on dialysis, undergoing kidney transplantation, or having eGFR <15 mL/min per 1.73 m2	12 months
Change From Baseline Cortisol Suppression at 9 Months	Cortisol suppression at 9 and 12 months, measured as urinary cortisol excretion over 24 hours compared to baseline.	Baseline & 9 months
Change From Baseline Cortisol Suppression at 12 Months	Cortisol suppression at 9 and 12 months, measured as urinary cortisol excretion over 24 hours compared to baseline.	Baseline & 12 months
Change From Baseline Short Form 36 (SF-36) Quality of Life Assessment at 12 Months	Short Form 36 (SF-36) quality of life assessment at 12 months compared to baseline, i.e. change from baseline. The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting and have been widely used. It consists of eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Higher scores indicate better health. Scores represent the percentage of total possible score achieved, i.e. 0 is the minimum and 100 is the maximum score.	Baseline & 12 months

Collaborators and Investigators

• Sponsor: Calliditas Therapeutics AB
• Investigators: Study Director: Richard Philipson, MD, Calliditas Therapeutics AB

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2020
• Primary Completion (Actual): February 26, 2024
• Study Completion (Actual): February 26, 2024

Study Registration Dates

• First Submitted: September 1, 2020
• First Submitted That Met QC Criteria: September 1, 2020
• First Posted (Actual): September 9, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 23, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Nephritis; Kidney Diseases; Glomerulonephritis, IGA
• Other Study ID Numbers: Nef-301 OLE; 2020-003308-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No