Clinical Trial Results:
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
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Summary
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EudraCT number |
2020-003308-14 |
Trial protocol |
CZ SE PL BE FR GB GR FI IT |
Global end of trial date |
24 Apr 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Dec 2024
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First version publication date |
25 Dec 2024
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
Nef-301OLE
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04541043 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Calliditas Therapeutics AB
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Sponsor organisation address |
Kungsbron 1, D5, Stockholm, Sweden, 111 22
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Public contact |
Clinical Operations, Calliditas Therapeutics AB, +46 737456451, kristin.onnestam@calliditas.com
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Scientific contact |
Clinical Operations, Calliditas Therapeutics AB, +46 737456451, kristin.onnestam@calliditas.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
26 Feb 2024
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
26 Feb 2024
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Global end of trial reached? |
Yes
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Global end of trial date |
24 Apr 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
•To assess the effect of 9 months of retreatment with Nefecon on urine protein to creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) in patients who completed Study Nef 301 with Nefecon treatment; and
•To assess the effect of 9 months of treatment with Nefecon on UPCR and eGFR in patients who completed Study Nef-301 with placebo treatment.
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Protection of trial subjects |
Open label study, all study patients received Nefecon 16 mg daily for 9 months. Regular visits to the study site with safety assessments. Possible to reduce dose at the discretion of the Investigator if warranted due to side effects.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Nov 2020
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Australia: 9
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Country: Number of subjects enrolled |
Argentina: 9
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Country: Number of subjects enrolled |
Belarus: 2
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Country: Number of subjects enrolled |
Canada: 14
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Country: Number of subjects enrolled |
Korea, Democratic People's Republic of: 6
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Country: Number of subjects enrolled |
Türkiye: 2
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Country: Number of subjects enrolled |
United States: 11
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Country: Number of subjects enrolled |
Poland: 3
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Country: Number of subjects enrolled |
Spain: 2
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Country: Number of subjects enrolled |
Sweden: 3
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Country: Number of subjects enrolled |
United Kingdom: 6
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Country: Number of subjects enrolled |
Belgium: 7
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Country: Number of subjects enrolled |
Czechia: 15
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Country: Number of subjects enrolled |
Finland: 4
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Country: Number of subjects enrolled |
France: 4
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Country: Number of subjects enrolled |
Germany: 11
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Country: Number of subjects enrolled |
Greece: 8
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Country: Number of subjects enrolled |
Italy: 3
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Worldwide total number of subjects |
119
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EEA total number of subjects |
60
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
116
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
Study participants completing the Nef-301 study and fulfilling inclusion/exclusion criteria for the Nef-301-OLE study were invited to be seamlessly enrolled in this open label study where all study participants received treatment with 16 mg Nefecon daily treatment for 9 months. | ||||||||||||||
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Pre-assignment
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Screening details |
Study participants completing the Nef-301 study and fulfilling inclusion/exclusion criteria for the Nef-301-OLE study were invited to be seamlessly enrolled in this open label study where all study participants received treatment with 16 mg Nefecon daily treatment for 9 months. | ||||||||||||||
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Period 1
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Period 1 title |
Nefecon 16mg daily (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
Blinding implementation details |
Not applicable. Open label study.
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Arms
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Arm title
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Nefecon 16mg daily | ||||||||||||||
Arm description |
Nefecon 16 mg once daily for 9 months and 3 months follow-up (total study duration 12 months). | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Nefecon
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Nefecon 16 mg once daily by mouth for 9 months. Capsules to be swallowed whole.
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Baseline characteristics reporting groups
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Reporting group title |
Nefecon 16mg daily
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Retreatment - Previously Treated With Nefecon in Nef-301 Study
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Nef-301-OLE study is an extension study to the Nef-301 study. Study results are analyzed based on treatment in the previous Nef-301 study where patients were randomized to receive either Nefecon or Placebo. Thus, in this Nef-301-OLE study the patients are either retreated with Nefecon or receiving Nefecon for the first time
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Subject analysis set title |
Delayed Treatment - Previously Treated With Placebo in Nef-301
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Nef-301-OLE study is an extension study to the Nef-301 study. Study results are analyzed based on treatment in the previous Nef-301 study where patients were randomized to receive either Nefecon or Placebo. Thus, in this Nef-301-OLE study the patients are either retreated with Nefecon or receiving Nefecon for the first time.
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End points reporting groups
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Reporting group title |
Nefecon 16mg daily
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Reporting group description |
Nefecon 16 mg once daily for 9 months and 3 months follow-up (total study duration 12 months). | ||
Subject analysis set title |
Retreatment - Previously Treated With Nefecon in Nef-301 Study
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Nef-301-OLE study is an extension study to the Nef-301 study. Study results are analyzed based on treatment in the previous Nef-301 study where patients were randomized to receive either Nefecon or Placebo. Thus, in this Nef-301-OLE study the patients are either retreated with Nefecon or receiving Nefecon for the first time
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Subject analysis set title |
Delayed Treatment - Previously Treated With Placebo in Nef-301
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Nef-301-OLE study is an extension study to the Nef-301 study. Study results are analyzed based on treatment in the previous Nef-301 study where patients were randomized to receive either Nefecon or Placebo. Thus, in this Nef-301-OLE study the patients are either retreated with Nefecon or receiving Nefecon for the first time.
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End point title |
Ratio of Urine Protein to Creatine Ratio (UPCR) at 9 Months Compared to Baseline [1] | ||||||||||||
End point description |
These results are from the MMRM analysis.
Log-transformed post-baseline to baseline ratios at month 3, 6, 9, and 12 are analyzed using MMRM with Nef-301 treatment, visit,
Nef-301 treatment by visit interaction as fixed factors; and log-baseline and log-baseline by visit interaction as covariates;
and patient as a random effect. An unstructured covariance matrix is used to model the within-subject correlation of data. The
Kenward-Roger’s degrees-of-freedom adjustment is used. Geometric least squares (LS) means, ratio of geometric LS means, and 95%
confidence intervals (CIs) are transformed back into the original scale from MMRM estimates.
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End point type |
Primary
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End point timeframe |
9 months
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: There is no statistical comparison of groups since open-label single arm study. The presented results are from the MMRM analysis. Log-transformed post-baseline to baseline ratios at month 3, 6, 9, and 12 are analyzed using MMRM with Nef-301 treatment, visit, Nef-301 treatment by visit interaction as fixed factors; and log-baseline and log-baseline by visit interaction as covariates; and patient as a random effect. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Ratio of Estimated Glomerular Filtration Rate (eGFR) at 9 Months Compared to Baseline | ||||||||||||
End point description |
eGFR is calculated by the central laboratory using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
To handle missing data, multiple imputation (MI) is performed with 20 imputations in two steps: non-monotone followed by
monotone missing pattern. MI is based on log-transformed baseline, log-transformed post-baseline at month 3, 6, 9, and 12. For
each imputation dataset, ratio of eGFR at each post-baseline visit to baseline is analyzed using Robust Regression with
independent variables of Nef-301 treatment and log-transformed baseline eGFR. M-estimation is used with Huber weights and a cut-off value of 2 with the median method used to estimate the scale parameter. Results averaged over imputations using Rubin’s
rules. Estimated means, ratio of estimated geometric means, and 95% confidence intervals (CIs) are transformed back into the
original scale from M-estimates.
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End point type |
Secondary
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End point timeframe |
9 months
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Ratio of Urine Albumin to Creatinine Ratio (UACR) at 9 Months Compared to Baseline | ||||||||||||
End point description |
Log-transformed post-baseline to baseline ratios at month 3, 6, 9, and 12 are analyzed using MMRM with Nef-301 treatment, visit,
Nef-301 treatment by visit interaction as fixed factors; and log-baseline and log-baseline by visit interaction as covariates;
and patient as a random effect. An unstructured covariance matrix is used to model the within-subject correlation of data. The
Kenward-Roger’s degrees-of-freedom adjustment is used. Geometric least squares (LS) means, ratio of geometric LS means, and 95%
confidence intervals (CIs) are transformed back into the original scale from MMRM estimates.
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End point type |
Secondary
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End point timeframe |
9 months
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Short Form 36 (SF-36) Quality of Life Assessment at 12 Months Compared to Baseline | ||||||||||||||||||||||||||||||||||||||||||
End point description |
Short Form 36 (SF-36) quality of life assessment at 12 months compared to 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. 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 score indicates better health. Score represent the percentage of total possible score achieved.
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End point type |
Secondary
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End point timeframe |
12 months
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Proportion of Patients With Microhematuria at 9 Months Compared to Baseline | |||||||||
End point description |
Patients with microhematuria at baseline is defined as patients’ urine dipstick result returns a valid result excluding any of
the following results at the last visit prior to first dose of OLE study drug: negative, trace, or 0.03 mg/dL.
Patients with microhematuria at specified post-baseline visit is defined as patients’ urine dipstick result returns a valid
result excluding any of the following results during the corresponding visit window: negative, trace, or 0.03 mg/dL.
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End point type |
Secondary
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End point timeframe |
9 months
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| No statistical analyses for this end point | ||||||||||
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End point title |
Proportion of Patients Receiving Rescue Treatment | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
12 months
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| No statistical analyses for this end point | ||||||||||
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End point title |
Proportion of Patients on Dialysis, Undergoing Kidney Transplantation, or With eGFR <15 mL/Min Per 1.73 m2 | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
12 months
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| No statistical analyses for this end point | ||||||||||
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End point title |
Cortisol Suppression at 9 Months Compared to Baseline | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
9 months
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Cortisol Suppression at 12 Months Compared to Baseline | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
12 months
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
All SAEs are reported from date of informed consent until end of study (approximately 13 months). Non-serious AEs are reported from date of first dose of study treatment to 14 days after the last dose of study treatment (approximately 10 months).
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.0
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Reporting groups
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Reporting group title |
Retreatment - Previously Treated With Nefecon in Nef-301 Study
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Reporting group description |
Nef-301-OLE study is an extension study to the Nef-301 study. Study results are analyzed based on treatment in the previous Nef-301 study where patients were randomized to receive either Nefecon or Placebo. Thus, in this Nef-301-OLE study the patients are either retreated with Nefecon or receiving Nefecon for the first time. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Delayed Treatment - Previously Treated With Placebo in Nef-301
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Reporting group description |
Nef-301-OLE study is an extension study to the Nef-301 study. Study results are analyzed based on treatment in the previous Nef-301 study where patients were randomized to receive either Nefecon or Placebo. Thus, in this Nef-301-OLE study the patients are either retreated with Nefecon or receiving Nefecon for the first time. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
