Efficacy and Safety of Nefecon in Patients With Primary IgA (Immunoglobulin A) Nephropathy

Calliditas Therapeutics AB365 enrolled

Overview

The overall aim of the study is to evaluate the efficacy, safety, and tolerability of Nefecon 16 mg per day in the treatment of patients with primary IgAN (Immunoglobulin A nephropathy) at risk of progressing to end-stage renal disease (ESRD), despite maximum tolerated treatment with renin-angiotensin system (RAS) blockade using angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II type I receptor blockers (ARBs).

This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy, safety, and tolerability of oral Nefecon compared to matching placebo in patients with primary IgAN on a background of optimized RAS inhibitor therapy. The study will consist of 2 parts, Part A and Part B. Part A will include a 9 month blinded Treatment Period, and a 3-month Follow up Period. Part B of the study will consist of a 12-month observational Follow up Period; no study drug will be administered during Part B. Part A and B will be blinded. Safety will be monitored by an independent Data Safety Monitoring Board.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

365

Conditions

Primary IgA Nephropathy

Interventions

NefeconDRUG

Nefecon 16 mg for daily administration by mouth for 9 months.

Placebo oral capsuleDRUG

Placebo capsules for daily administration by mouth for 9 months.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Female or male patients ≥18 years 2. Biopsy-verified IgA nephropathy 3. Stable dose of RAS inhibitor therapy (ACEIs and/or ARBs) at the maximum allowed dose or Maximum Tolerated Dose (MTD) according to the 2012 KDIGO (Kidney Disease: Improving Global Outcomes) guidelines 4. Urine protein creatinine ratio ≥1 g/24hr 5. eGFR ≥35 mL/min per 1.73 m2 and ≤90 mL/min per 1.73 m2 using the Chronic Kidney Diseae Epidemiology Collaboration (CKD-EPI) formula 6. Willing and able to give informed consent Exclusion Criteria: 1. Systemic diseases that may cause mesangial IgA deposition. 2. Patients who have undergone a kidney transplant. 3. Patients with acute or chronic infectious disease including hepatitis, tuberculosis, human immunodeficiency virus (HIV), and chronic urinary tract infections. 4. Patients with liver cirrhosis, as assessed by the Investigator. 5. Patients with a diagnosis of type 1 or type 2 diabetes mellitus which is poorly controlled. 6. Patients with history of unstable angina, class III or IV congestive heart failure, and/or clinically significant arrhythmia, as judged by the Investigator; 7. Patients with unacceptable blood pressure control defined as a blood pressure consistently above national guidelines for proteinuric renal disease, as assessed by the Investigator 8. Patients with diagnosed malignancy within the past 5 years.

Locations (142)

Outcomes

Primary Outcomes

Part A: Ratio of Urine Protein to Creatinine Ratio (UPCR) at 9 Months Compared to Baseline

Part A primary endpoint: The ratio of Urine Protein to Creatinine Ratio (UPCR) (based on 24-hour urine collections) at 9 months following the first dose of study drug compared to baseline. Ratio being: UPCR at 9 months in g/gram divided with UPCR at Baseline in g/gram

Time frame: 9 months

Part B: Time-weighted Average of Estimated Glomerular Filtration Rate (eGFR)

Part B Primary endpoint: Time-weighted average of estimated glomerular filtration rate (eGFR) recordings observed at each time point over 2 years. The eGFR (CKD-EPI) at 2 years (which must have been repeated to provide a second value obtained within 14 to 35 days) was the geometric mean of the 2 assessments.

Time frame: Up to 2 years and 1 month

Secondary Outcomes

Part A: Ratio of eGFR at 9 Months

Part A: Ratio of eGFR at 9 months compared to baseline calculated using the CKD-EPI formula.

Time frame: 9 months

Part A: Ratio of eGFR at 12 Months

Part A: Ratio of eGFR at 12 months compared to baseline calculated using the CKD-EPI formula.

Time frame: 12 months

Part A: Ratio of Urine Albumin to Creatinine Ratio (UACR) at 9 Months

Part A: Ratio of urine albumin to creatinine ratio (UACR) at 9 months compared to baseline.

Time frame: 9 months

Part B: Time to 30% Reduction in eGFR

Part B: Time to 30% reduction from baseline in eGFR (CKD-EPI) confirmed by a second value. For clarity: Please note that the number of patients with a 30% reduction is presented with statistical analysis of the time to 30% reduction.

Data from ClinicalTrials.gov

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University of Alabama at Birmingham, 1720 2nd Ave South

Birmingham, Alabama, United States

Univ of Arizona, 1501 N Campbell Ave

Tucson, Arizona, United States

Stanford University Medical Center, 777 Welch Rd

Palo Alto, California, United States

Los Angeles Biomedical Research Institute at HUMC, 1124 W. Carson Street

Torrance, California, United States

University of Colorado Health Science Center, 1200 East 19th Av.

Aurora, Colorado, United States

Western Nephrology and Metabolic Bone Disease, PC-Westerminster, 8410 Decatur St.

Westminster, Colorado, United States

Yale University School of Medicine, 330 Cedar Street

New Haven, Connecticut, United States

Washington Nephrology Associates-Washington DC, 730 24th Street NW

Washington D.C., District of Columbia, United States

University of Florida-Gainesville

Gainesville, Florida, United States

Omega Research Maitland, 7912 Forest City Rd.

Orlando, Florida, United States

...and 132 more locations

Time frame: Over 2 years

Part B: Time to Receiving Rescue Medication.

Part B: Time from the first dose of study drug until receiving rescue medication. For clarity: Please note that the number of patients receiving rescue medication is presented with statistical analysis of the time to receiving rescue medication.

Time frame: Over 2 years

Part B: Ratio of UPCR Compared to Baseline Averaged Over Time Points Between 12 and 24 Months

Part B: Ratio of UPCR, UACR, and eGFR (CKD-EPI) compared to baseline averaged over time points between 12 and 24 months, inclusive, following the first dose of study drug

Time frame: 12, 18 and 24 months

Part B: Ratio of UACR Compared to Baseline Averaged Over Time Points Between 12 and 24 Months

Part B: Ratio of UPCR, UACR, and eGFR (CKD-EPI) compared to baseline averaged over time points between 12 and 24 months, inclusive, following the first dose of study drug.

Time frame: 12 to 24 months

Part B: Ratio of eGFR Compared to Baseline Averaged Over Time Points Between 12 and 24 Months

Part B: Ratio of UPCR, UACR, and eGFR (CKD-EPI) compared to baseline averaged over time points between 12 and 24 months, inclusive, following the first dose of study drug;

Time frame: 12 to 24 months

Part B: Proportion of Patients Without Microhematuria

Part B: Proportion of patients without microhematuria in at least 2 of the following time points: 12, 18, and 24 months following the first dose of study drug

Time frame: 12 to 24 months

Part B: Short Form 36 (SF-36) Quality of Life Assessment at 9 Months.

Part B: Short Form 36 (SF-36) quality of life assessment at 9 and 24 months. 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.

Time frame: 9 months

Part B: Short Form 36 (SF-36) Quality of Life Assessment at 24 Months.

Time frame: 24 months