Nefecon in patients with Primary IGA-Nephropathy Calliditas
Research type
Research Study
Full title
A Randomized, Double-Blind, Placebo Controlled Study to Evaluate Efficacy and Safety of Nefecon in Patients with Primary IgA Nephropathy at Risk of Progressing to End-Stage Renal Disease (NefIgArd).
IRAS ID
242354
Contact name
Chee Kay Cheung
Contact email
Sponsor organisation
Calliditas Therapetuics AB
Eudract number
2017-004902-16
Clinicaltrials.gov Identifier
Duration of Study in the UK
4 years, 6 months, 0 days
Research summary
Research Summary
Nefecon is an investigational medicinal product being developed by Calliditas Therapeutics AB as a modified-release (MR) capsule, and is being studied for the treatment of patients with primary immunoglobulin A (IgA) nephropathy (IgAN)(Also known as Berger Disease) at risk of developing end-stage renal disease (ESRD). Primary IgA Nephropathy is a kidney disease caused by an abnormal antibody (a type of protein) called Immunoglobulin A (IgA), and is the most common cause of glomerulonephritis worldwide, with estimates varying from 5% to more than 40% of patients with glomerular disease. Additionally, patients with a more severe form of the disease are at risk of progressing to end-stage renal disease.
This is a Global Phase 3 study, patients are expected to be enrolled at 150 sites across Europe, North America, South America, and Asia Pacific. The study consists of 2 parts, Part A and Part B. Part A (which includes a 35 day screening period) will last approximately 12 months, with a 9 month treatment period and 3 months follow-up period. Part B of the study will consist of an observational long-term follow-up period expected to last for 6 years after the first participant was randomised.
The primary objective of this study is to evaluate the efficacy, safety, and tolerability of Nefecon 16mg per day in the treatment of patients with IgAN 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 blocker (ARBs).
Summary of Results
A study of Nefecon in adults with a kidney disease named primary immunoglobulin A nephropathy Full study title: A Randomized, Double-Blind, Placebo Controlled Study to Evaluate Efficacy and Safety of Nefecon in Patients with Primary IgA Nephropathy at Risk of Progressing to End-Stage Renal Disease (NefIgArd)
Calliditas Therapeutics AB, the Sponsor, would like to thank the participants in this clinical study for their time and effort. Study participation allows Calliditas Therapeutics AB, and the doctors, nurses, and study staff responsible for the study, to examine how well Nefecon works and how safe it is when treating patients with primary IgA nephropathy at risk of progressing to end-stage renal disease.
1. GENERAL INFORMATION ABOUT THE STUDY/WHY WAS THIS STUDY DONE?
This was a study to understand if the medicine Nefecon would be helpful and safe as treatment for adults with a kidney disease called primary immunoglobulin A (IgA) nephropathy (IgAN) who are at risk for their disease getting worse. IgAN happens when the antibody IgA is not made properly, and clumps of antibodies get stuck in the kidneys and cause inflammation and kidney damage. This results in increased levels of protein in the urine (proteinuria), and risk of decline in kidney function.
Nefecon is a capsule specially modified to deliver the corticosteroid budesonide locally in the small intestine where the defective IgA is produced. Budesonide is a well-known medicine, used for over 40 years to treat asthma, Crohn’s disease, and other diseases.
Nefecon was an investigational drug when the study started. The data collected during the study was used to gain accelerated approval for Nefecon in December 2021 in the United States (US) (branded as TARPEYO®) to reduce proteinuria, and full approval in the US in December 2023 to reduce loss of kidney function in adults who are at risk for worsening of kidney function. Nefecon gained conditional approval in July 2022 in the European Union (EU) and in February 2023 in the UK (branded as Kinpeygo®); it also gained conditional approval in October 2023 in Macao, in November 2023 in China, and in March 2024 in Singapore (branded as NEFECON®) to reduce proteinuria in adults with primary IgAN who are at high risk of worsening (disease progression).
The main purposes of the study were to look at:
• How well Nefecon worked for the treatment of IgAN, using the “estimated glomerular filtration rate” or eGFR. eGFR is a calculation of the function of the kidneys. It measures the amount of blood that is filtered per minute (amount of mL per minute per 1,73 m2, as the formula takes body size into account). The higher the number, the better the kidney function.The eGFR of study participants taking Nefecon was calculated during the 2 years of study duration and compared to eGFR in participants taking placebo. A placebo looks like the study drug (Nefecon), but it does not contain any active ingredient. We refer to both Nefecon and placebo as “study medicine” in this document.
• How safe Nefecon was when compared to placebo.
2. WHEN AND WHERE WAS THE STUDY DONE?
When was it performed?
This study started in September 2018 and ended in June 2023.
Where did the study take place?
The study took place in the following countries – number of participants for each country in brackets:Argentina (18), Australia (21), Belarus (7), Belgium (15), Canada (24) , China (62), Czech Republic (31) , Finland (7), France (10), Germany (33), Greece (24), Italy (6), Poland (7), South Korea (20), Spain (8), Sweden (11), Taiwan (2), Turkey (21), United Kingdom (19), United States (49).
3. WHO TOOK PART IN THIS STUDY?
Male and female participants in the study had to meet the following criteria among others:
• be 18 years or older;
• be diagnosed with IgAN;
• had proteinuria despite being under the standard treatment (named RAS inhibitor therapy) for at least 3 months before receiving the study medicine.
4. WHICH MEDICINES WERE STUDIED?
Nefecon 16 mg (taken as 4 capsules, 4 mg each), and placebo capsules were provided to be taken by mouth (orally), once a day, in the morning (approximately 1 hour before breakfast). All participants had to continue with the standard treatment for IgAN (RAS inhibitor therapy) during the study.
5. HOW WAS THE STUDY DONE?
The study had 2 consecutive parts, Part A and Part B. Participants started in Part A, where they were assigned randomly (by chance, like flipping a coin) to receive either Nefecon or placebo, for 9 months. Participants had a 50% chance of receiving Nefecon and a 50% chance of receiving placebo. Double-blind means that neither the participant nor the research team knew which treatment the participant received until the end of the study.
Then, participants were followed for about 1 year and 3 months in Part B of the study, where no study medicine was given. The maximum duration of study participation was about 2 years and 2 months. Several procedures were done during the study visits, including blood and urine tests, questionnaires, and physical examinations.
6. WHAT WERE THE MAIN RESULTS OF THE STUDY?
The results from the study showed that the 9 months treatment with Nefecon reduced the loss of kidney function:
• The eGFR values over the 2-year study period were significantly higher (on average 5 mL/min/1.73 m2 higher) in patients treated with Nefecon than in patients receiving placebo.
• The average reduction of eGFR per year was 3.55 mL/min/1.73 m2/year in patients treated with Nefecon and 5.37 mL/min/1.73 m2/year in patients receiving placebo.
• The amounts of protein in urine (proteinuria) decreased by an average of 34 % after 9 months of treatment with Nefecon (for example, going from 100 to 66). While proteinuria decreased by an average of 5% (for example, going from 100 to 95) after receiving the placebo.
7. WERE THERE ANY UNWANTED EFFECTS?
Overall, Nefecon was well tolerated in this study. The unwanted effects seen were as expected for an oral delayed release budesonide product.
The most common side effects of Nefecon included (seen in more than 5 of every 100 participants of the Nefecon group (or more than 5%):
• swelling of the lower legs, ankles, and feet
• high blood pressure
• muscle spasms
• acne
• headache
• upper respiratory tract infection
• swelling of the face
• weight increase
• indigestion
• irritation or inflammation of the skin
• joint pain
• increased white blood cell count
Other side effects associated with corticosteroids seen at lower frequencies included rounding of the face, thicker or more hair on the body and face, and purple stretch marks.
8. HOW HAS THE STUDY HELPED PATIENTS AND RESEARCHERS?
The results from the study enabled for approvals of Nefecon in the US, EU, and Asia, as treatment for proteinuria in adult patients with primary IgAN at high risk of worsening.
9. ARE THERE ANY PLANS FOR FUTURE STUDIES?
There is a possibility for future studies of Nefecon on IgAN.10. WHERE CAN I FIND OUT MORE INFORMATION ABOUT THIS STUDY?
• Protocol Title: A Randomized, Double-Blind, Placebo Controlled Study to Evaluate Efficacy and Safety of Nefecon in Patients with Primary IgA Nephropathy at risk of Progressing to End-Stage Renal Disease (NefIgArd)
• Protocol No.: Nef-301
• EudraCT No.: https://www.clinicaltrialsregister.eu/ and use the study identifier: 2017-004902-16
• Clinicaltrials.gov: https://www.clinicaltrials.gov/ and use the study identifier: 03643965
• Sponsor: Calliditas Therapeutics AB - Kungsbron 1 SE-111 22, Stockholm, Sweden +46 8 411 3005
• Date of this report: 16th April 2024REC name
West of Scotland REC 1
REC reference
18/WS/0073
Date of REC Opinion
29 May 2018
REC opinion
Further Information Favourable Opinion