NEFECON IN PATIENTS WITH PRIMARY IGA-Nephropathy Phase 3b OLE Study
Research type
Research Study
Full 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
IRAS ID
287861
Contact name
Chee Kay Cheung
Contact email
Sponsor organisation
Calliditas Therapeutics AB
Eudract number
2020-003308-14
Duration of Study in the UK
3 years, 3 months, 23 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 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).
Assuming that 75% of the patients who have completed Study Nef-301 will enter Study Nef-301 OLE, the total number of patients to be included is estimated to be approximately 250 patients, but up to 360 patients may be enrolled.
Summary of results
Study in which Efficacy and Safety of Nefecon is evaluated in Patients With IgA Nepropathy Who Have Completed Study Nef-301
Full study 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
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 in treating people with a kidney disease named primary IgA nephropathy (IgAN). Participants in this clinical study has previously participated in the study Nef-301.
1. GENERAL INFORMATION ABOUT THE STUDY/WHY WAS THIS STUDY DONE?
This was an Open Label Extension (OLE) study that followed after the Nef-301 study. In the Nef-301 study, half of the participants received Nefecon and the other half placebo (which looked like Nefecon, but it did not contain any active ingredient). Participants were “blinded”, meaning they did not know which treatment they received. All participants who completed the Nef-301 study and had high proteinuria (increased levels of protein in the urine) could take part in the OLE (Nef-301OLE) study and remained blinded to the treatment received in Nef-301. The Nef-301OLE study was an Open Label study, which means that all participants knew they received Nefecon.
The study was done to see if the medicine Nefecon would be helpful and safe as treatment for adults with IgAN. IgAN happens when the antibody IgA is not made properly, and clumps of antibodies get stuck in the kidneys. This causes inflammation and kidney damage, resulting in proteinuria and risk of decline in kidney function.
Nefecon is a capsule specially designed 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 medicine when the previous study (Nef-301) started, but gained approval in some countries while this OLE study was ongoing.The main purposes of the study were to look at:
• How well Nefecon worked for the treatment of IgAN, measuring proteinuria levels and 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.
• How safe Nefecon was.
Both purposes were studied in 119 participants who had previously received Nefecon or placebo in the former Nef-301 study.2. WHEN AND WHERE WAS THE STUDY DONE?
When was it performed?
This study started in November 2020 and ended in February 2024.
Where did the study take place?
The study took place in the following countries with the following number of participants:
• Argentina: 9
• Australia: 9
• Belarus:2
• Belgium:7
• Canada:14
• Czech Republic:15
• Finland:4
• France:4
• Germany:11
• Greece:8
• Italy:3
• Poland:3
• South Korea:6
• Spain:2
• Sweden:3
• Turkey:2
• United Kingdom:6
• United States:113. WHO TOOK PART IN THIS STUDY?
Male and female participants in the study had to meet the following criteria among others:
• having completed 9 months of treatment with Nefecon or placebo, and a 15 months follow-up period in the previous study Nef-301. (Participants in Nef-301 had to be diagnosed with IgAN).
• be under a stable optimised standard treatment with RAS inhibitor therapy.
• having proteinuria over (1g/day) and eGFR over (30mL/min).4. WHICH MEDICINES WERE STUDIED?
Nefecon 16 mg (taken as 4 capsules, 4 mg each) was 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?
Participants went through a screening period to see if they could be part of the study. Some of the screening visits were combined with the last visit of prior study Nef-301 so that procedures did not need to be repeated. Participants then entered the treatment period and received Nefecon for 9 months followed by a 3-months follow-up period. The maximum time participants could be in the study was about 14,5 months (about 1 year 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 this study showed that regardless of whether patients received retreatment with Nefecon or initial treatment with Nefecon, there was clear proteinuria and eGFR benefit after 9 months of Nefecon treatment in the Nef-301OLE study:
• The amounts of protein in urine (proteinuria) decreased by an average of 32 % after 9 months of treatment with Nefecon.
• The eGFR value showed a stabilization after the 9-month treatment period. eGFR was reduced 1.43 mL/min/1.73 m2 on average, from the eGFR value before starting the study.7. WHERE 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.
Adverse reactions are unwanted effects, considered related to Nefecon by the investigator. The most common side effects of Nefecon included (seen in more than 5 of every 100 participants (or more than 5%)):
• high blood pressure,
• acne,
• weight increase,
• rounding of the face (Cushingoid),
• trouble falling asleep (insomnia),
• muscle spasms,
• swelling of the lower legs, ankles, and feet8. HOW HAS THE STUDY HELPED PATIENTS AND RESEARCHERS?
The results from this study showed proteinuria and eGFR benefit after 9 months of Nefecon treatment. However, this summary only shows the results from this study, which may be different to the results from other studies.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: 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
• Protocol No.: Nef-301 OLE
• Clinicaltrials.gov: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3t%2Fwww.ClinicalTrials.gov%2FNBTI%2FG264AQ%2FAQ%2Fb3a89e83-9c67-4dc1-97f3-83d197d279a8%2F1%2FAPzMkgsSn-&data=05%7C02%7Cfulham.rec%40hra.nhs.uk%7C6a17ca2f30ad4f3e10ef08dce39b745a%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638635504004156618%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=M7FHAsz7MYdA3PWJEScYy9i8wg4gSQTdq8Y6c65P%2B9E%3D&reserved=0
• Use the study identifier: NCT04541043
• EudraCT No.: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fwww.clinicaltrialsregister.eu%2FNBTI%2FG264AQ%2FAQ%2Fb3a89e83-9c67-4dc1-97f3-83d197d279a8%2F2%2FT5tt-e9Non&data=05%7C02%7Cfulham.rec%40hra.nhs.uk%7C6a17ca2f30ad4f3e10ef08dce39b745a%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638635504004174564%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=KvFxaFgW4NDmkfwl%2F3qCnbkeffTu3iKTlrmaYbP3d3M%3D&reserved=0
• Use the study identifier: 2020-003308-14
• Sponsor: Calliditas Therapeutics AB - Kungsbron 1 C8, 111 22 - Stockholm, Sweden +46 8 411 3005
• Date of this report: 5th September 2024Thank You
Calliditas Therapeutics AB wants to thank all the participants for their time and effort that went into making this study possible. Clinical study participants help advance science
REC name
London - Fulham Research Ethics Committee
REC reference
20/LO/1059
Date of REC Opinion
30 Oct 2020
REC opinion
Further Information Favourable Opinion