Lupus Nephritis
Conditions
Keywords
Lupus Nephritis, secukinumab (AIN457), estimated glomerular filtration rate, Urine Protein-to-Creatinine Ratio, Standard of Care background therapy
Brief summary
The purpose of this open-label extension study was to provide treatment with secukinumab for subjects who completed core study treatment in Study CAIN457Q12301 (NCT04181762), and to obtain further data on long-term efficacy, safety and tolerability of secukinunab in patients with active lupus nephritis (LN).
Detailed description
Investigators used their clinical judgement to decide if it might be beneficial, in terms of overall improvement and response to therapy, for subjects to enter the extension study. The planned total combined duration for the core study and this extension study was five years. At Week 104 of the core study CAIN457Q12301, eligible subjects who completed the assessments associated with the core study visit subsequently continued in the extension study on the dose of secukinumab 300 mg administered every four weeks. A total of 31 subjects were enrolled and received secukinumab 300 mg every four weeks until study termination. Recruitment in this study was stopped on 26-May-2023. This study along with the core study (CAIN457Q12301) were terminated early by Novartis due to futile results of interim analysis 1 of the core study. There were no safety related reasons for early termination of either of the studies.
Interventions
DRUGSecukinumab
300 mg solution for subcutaneous (s.c.) injection in a 2mL Pre-Filled Syringe (PFS)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key inclusion criteria: * Subject must have both participated in core study and completed the entire treatment period up to and including Week 104 of the core study CAIN457Q12301. * Subject must be deemed by the investigator to benefit from secukinumab therapy. * Signed informed consent must be obtained prior to participation in the study. Key
Exclusion criteria
* Any subject taking other concomitant biologic immunomodulating agent(s) except secukinumab. * Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test. * Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during the entire study or longer if required by locally approved prescribing information (e.g., in European Union (EU) 20 Weeks). Highly effective methods of contraception are recommended due to the known teratogenic effect of SoC (MPA).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Complete Renal Response (CRR) | Up to 28 weeks: from enrollment in the extension study (Week 104E1) up to Week 132 or Early termination of the Extension Study. Study day is defined with respect to the core study. | Complete Renal Response (CRR) is a composite endpoint defined as: * Estimated Glomerular Filtration Rate (eGFR) \>= 60 mL/min/1.73 m\^2 or no less than 85% of core Baseline values and * 24-hour Urine-to-Protein Creatinine Ratio (UPCR) =\< 0.5mg/mg The glomerular filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on subject gender, age (years) and serum creatinine (mg/dL). Central laboratory serum creatinine values were used for all renal function data analysis. UPCR was determined by a central laboratory by dividing the protein concentration by the creatinine concentration as measured in the urine collected. UPCR was determined using one of the following two types of urine collection, 24-hour urine collection or first morning void urinary sample, both of which were collected in the subjects' home. |
Countries
Australia, Brazil, Colombia, Czechia, Guatemala, Japan, Philippines, Portugal, Slovakia, South Korea, Spain, Thailand, Vietnam
Participant flow
Recruitment details
This study was conducted in 18 centers in 13 countries: Australia (1 site), Brazil (2 sites), Colombia (1 site), Czech Republic (2 sites), Guatemala (2 sites), Japan (2 sites), Korea (1 site), Republic of Philippines (1 site), Portugal (2 sites), Slovakia (Slovak Republic) (1 site), Spain (1 site), Thailand (1 site), Vietnam (1 site)
Participants by arm
| Arm | Count |
|---|---|
| Secukinumab 300 mg Patients who were on Secukinumab 300 mg in the Core Study (CAIN457Q12301) and continued treatment with Secukinumab 300 mg every four weeks in the Extension Study until study termination notification (maximum treatment exposure during the extension study: 281 days) | 16 |
| Placebo to Secukinumab 300 mg Patients who were on Placebo in the Core Study (CAIN457Q12301) and continued treatment with Secukinumab 300 mg every four weeks in the Extension Study until study termination notification (maximum treatment exposure during the extension study: 310 days) | 15 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Study terminated by sponsor | 16 | 14 |
Baseline characteristics
| Characteristic | Secukinumab 300 mg | Placebo to Secukinumab 300 mg | Total |
|---|---|---|---|
| Age, Continuous | 35.6 Years STANDARD_DEVIATION 8.26 | 30.6 Years STANDARD_DEVIATION 9.83 | 33.2 Years STANDARD_DEVIATION 9.26 |
| Age, Customized < 30 years | 4 Participants | 7 Participants | 11 Participants |
| Age, Customized >= 30 years | 12 Participants | 8 Participants | 20 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 6 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 8 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 6 Participants | 8 Participants |
| Sex: Female, Male Female | 14 Participants | 14 Participants | 28 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 15 |
| other Total, other adverse events | 15 / 16 | 15 / 15 |
| serious Total, serious adverse events | 4 / 16 | 8 / 15 |
Outcome results
Primary
Percentage of Participants Achieving Complete Renal Response (CRR)
Complete Renal Response (CRR) is a composite endpoint defined as: * Estimated Glomerular Filtration Rate (eGFR) \>= 60 mL/min/1.73 m\^2 or no less than 85% of core Baseline values and * 24-hour Urine-to-Protein Creatinine Ratio (UPCR) =\< 0.5mg/mg The glomerular filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on subject gender, age (years) and serum creatinine (mg/dL). Central laboratory serum creatinine values were used for all renal function data analysis. UPCR was determined by a central laboratory by dividing the protein concentration by the creatinine concentration as measured in the urine collected. UPCR was determined using one of the following two types of urine collection, 24-hour urine collection or first morning void urinary sample, both of which were collected in the subjects' home.
Time frame: Up to 28 weeks: from enrollment in the extension study (Week 104E1) up to Week 132 or Early termination of the Extension Study. Study day is defined with respect to the core study.
Population: Full Analysis Set. Percentages were calculated based on the number of participants with an assessment at the specified time point independently if subject was still on treatment or discontinued from treatment before that timepoint.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Secukinumab 300 mg | Percentage of Participants Achieving Complete Renal Response (CRR) | Week 104E1 (Baseline Extension Study) (n = 9, 9) | 4 Participants |
| Secukinumab 300 mg | Percentage of Participants Achieving Complete Renal Response (CRR) | Week 132 (n = 6, 5) | 3 Participants |
| Placebo to Secukinumab 300 mg | Percentage of Participants Achieving Complete Renal Response (CRR) | Week 104E1 (Baseline Extension Study) (n = 9, 9) | 5 Participants |
| Placebo to Secukinumab 300 mg | Percentage of Participants Achieving Complete Renal Response (CRR) | Week 132 (n = 6, 5) | 5 Participants |