Clinical Trials List
Protocol NumberCAIN457Q12301
2020-08-01 - 2023-06-26
Phase III
Recruiting4
ICD-10E10.21
Type 1 diabetes mellitus with diabetic nephropathy
ICD-10E11.21
Type 2 diabetes mellitus with diabetic nephropathy
ICD-10N16
Renal tubulo-interstitial disorders in diseases classified elsewhere
ICD-9583.81
Nephritis and nephropathy, not specified as acute or chronic, in diseases classified elsewhere
A two-year, phase III randomized, double-blind, parallel-group, placebocontrolled trial to evaluate the safety, efficacy, and tolerability of 300 mg s.c. secukinumab versus placebo, in combination with SoC therapy, in patients with active lupus nephritis
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Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
-
Sponsor
Novartis
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 謝祖怡 無
- 吳沂達 無
- 黃文男、謝佳偉、謝祖怡、林靖才、洪維廷、陳信華、吳沂達、譚國棟、陳一銘 無
- 謝佳偉 無
- HSIN-HUA CHEN 無
- WEN-NAN HUANG 無
- 洪維廷 未分科
- Yi-Ming Chen 未分科
- Yi-Ming Chen 無
- 林靖才 無
- 譚國棟 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chen Der-Yuan 無
- 黃建中 無
- Po-Hao Huang 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
active lupus nephritis
Objectives
The purpose of this trial is to evaluate the efficacy and safety of subcutaneous secukinumab 300 mg compared to placebo, in combination with standard of care therapy (SoC), in subjects with active lupus nephritis (ISN/RPS Class III or IV, with or without co-existing class V features). Background SoC will consist of induction therapy with mycophenolic acid (MPA) (which refers to Mycophenolate mofetil (MMF) (Cellcept® or generic equivalent), or enteric-coated MPA sodium (Myfortic® or generic equivalent) at equivalent doses (oral), or Cyclophosphamide (CYC) (i.v.), followed by maintenance therapy with MPA (MMF, enteric-coated MPA sodium, or their generics). In addition, all subjects will receive i.v. and/or oral corticosteroids.The aim of the study is to demonstrate the efficacy and safety of secukinumab in LN that will enable registration for the indication of lupus nephritis.
Test Drug
AIN457
Active Ingredient
AIN457 (Secukinumab)
Dosage Form
Solution for injection in pre-filled syringe (PFS)
Dosage
150mg /1mL
Endpoints
Primary Objective(s)
The primary objective is to demonstrate that secukinumab 300 mg is superior to placebo in Complete Renal Response (CRR) rate at Week 52 in active lupus nephritis (ISN/RPS Class III or IV, with or without co-existing Class V features) subjects on a background of SoC therapy
Secondary Objectives
Objective 1: To demonstrate superiority of secukinumab compared to placebo in
change from Baseline in 24-hour UPCR at Week 52
Objective 2: To demonstrate superiority of secukinumab compared to placebo in
proportion of subjects achieving partial renal response (PRR) at Week 52
Objective 3: To demonstrate superiority of secukinumab compared to placebo in
average daily dose of oral corticosteroids administered between Week 16 and
Week 52
Objective 4: To demonstrate superiority of secukinumab compared to placebo in
proportion of subjects achieving PRR at Week 24
Objective 5: To demonstrate superiority of secukinumab compared to placebo in
time to achieve CRR
Objective 6: To demonstrate superiority of secukinumab compared to placebo in
time to achieve PRR
Objective 7: To demonstrate superiority of secukinumab compared to placebo in
time to achieve first morning void Urine Protein-to-Creatinine Ratio (UPCR) ≤ 0.5
mg/mg
Objective 8: To demonstrate superiority of secukinumab compared to placebo in
change in Functional Assessment of Chronic Illness Therapy – Fatigue (FACITFatigue©) score at Week 52
Objective 9: To demonstrate superiority of secukinumab compared to placebo in
patient’s health related quality of life via Medical Outcome Short Form Health
Survey (SF-36 Physical Component Summary (PCS)) score at Week 52
Objective 10: To demonstrate superiority of secukinumab compared to placebo in
change of LupusQoL (Physical Health) score at Week 52
Objective 11: To evaluate the safety and tolerability of secukinumab s.c. as an
add-on therapy to Standard of Care in lupus nephritis subjects
Objective 12: To estimate the proportion of subjects with maintained renal
response at Week 104
Objective 13: To estimate the proportion of subjects with improved or maintained
renal response at Week 104
The primary objective is to demonstrate that secukinumab 300 mg is superior to placebo in Complete Renal Response (CRR) rate at Week 52 in active lupus nephritis (ISN/RPS Class III or IV, with or without co-existing Class V features) subjects on a background of SoC therapy
Secondary Objectives
Objective 1: To demonstrate superiority of secukinumab compared to placebo in
change from Baseline in 24-hour UPCR at Week 52
Objective 2: To demonstrate superiority of secukinumab compared to placebo in
proportion of subjects achieving partial renal response (PRR) at Week 52
Objective 3: To demonstrate superiority of secukinumab compared to placebo in
average daily dose of oral corticosteroids administered between Week 16 and
Week 52
Objective 4: To demonstrate superiority of secukinumab compared to placebo in
proportion of subjects achieving PRR at Week 24
Objective 5: To demonstrate superiority of secukinumab compared to placebo in
time to achieve CRR
Objective 6: To demonstrate superiority of secukinumab compared to placebo in
time to achieve PRR
Objective 7: To demonstrate superiority of secukinumab compared to placebo in
time to achieve first morning void Urine Protein-to-Creatinine Ratio (UPCR) ≤ 0.5
mg/mg
Objective 8: To demonstrate superiority of secukinumab compared to placebo in
change in Functional Assessment of Chronic Illness Therapy – Fatigue (FACITFatigue©) score at Week 52
Objective 9: To demonstrate superiority of secukinumab compared to placebo in
patient’s health related quality of life via Medical Outcome Short Form Health
Survey (SF-36 Physical Component Summary (PCS)) score at Week 52
Objective 10: To demonstrate superiority of secukinumab compared to placebo in
change of LupusQoL (Physical Health) score at Week 52
Objective 11: To evaluate the safety and tolerability of secukinumab s.c. as an
add-on therapy to Standard of Care in lupus nephritis subjects
Objective 12: To estimate the proportion of subjects with maintained renal
response at Week 104
Objective 13: To estimate the proportion of subjects with improved or maintained
renal response at Week 104
Inclution Criteria
Subjects eligible for inclusion in this study must meet all of the following
criteria:
1. Adult male and female subjects aged 18 - 75 years old at the time of
Baseline
2. Confirmed diagnosis of:
· SLE with documented history of at least 4 of the 11 criteria for SLE as
defined by the American College of Rheumatology (ACR). [NOTE: The 4
criteria do not have to be present at the time of Screening],
OR
· Lupus nephritis as the sole clinical criterion in the presence of ANA or antidsDNA antibodies.
3. Active lupus nephritis, as defined by meeting the 4 following criteria:
· Biopsy within 6 months prior to Screening visit indicating active
glomerulonephritis WHO or ISN/RPS Class III or IV LN [excluding III (C),
IV-S (C) and IV-G (C)]; subjects are permitted to have co-existing Class V.
If no biopsy was performed within 6 months of Screening, a biopsy will need
to be performed during the Screening period, after all other
inclusion/exclusion criteria would have been verified.
· UPCR ≥1 at Screening
· Estimated eGFR >30 mL/min/1.73 m2 by Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI)
· Active urinary sediment (presence of cellular casts (granular or red blood
cell casts) or hematuria (>5 red blood cells per high power field))
4. Subjects must be currently on, or willing to initiate SoC induction therapy
for LN according to the institutional practices using MPA (MMF or entericcoated MPA sodium) or low-dose CYC in addition to corticosteroids.
5. If the subject is on cholesterol-lowering agents, the dose must be stable
for at least 7 days prior to Randomization.
6. Subjects must be treated with anti-malarials (e.g., hydroxychloroquine),
unless contra-indicated, and the dose must be stable for at least 10 days prior
to Randomization.
7. Able to provide signed informed consent.
criteria:
1. Adult male and female subjects aged 18 - 75 years old at the time of
Baseline
2. Confirmed diagnosis of:
· SLE with documented history of at least 4 of the 11 criteria for SLE as
defined by the American College of Rheumatology (ACR). [NOTE: The 4
criteria do not have to be present at the time of Screening],
OR
· Lupus nephritis as the sole clinical criterion in the presence of ANA or antidsDNA antibodies.
3. Active lupus nephritis, as defined by meeting the 4 following criteria:
· Biopsy within 6 months prior to Screening visit indicating active
glomerulonephritis WHO or ISN/RPS Class III or IV LN [excluding III (C),
IV-S (C) and IV-G (C)]; subjects are permitted to have co-existing Class V.
If no biopsy was performed within 6 months of Screening, a biopsy will need
to be performed during the Screening period, after all other
inclusion/exclusion criteria would have been verified.
· UPCR ≥1 at Screening
· Estimated eGFR >30 mL/min/1.73 m2 by Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI)
· Active urinary sediment (presence of cellular casts (granular or red blood
cell casts) or hematuria (>5 red blood cells per high power field))
4. Subjects must be currently on, or willing to initiate SoC induction therapy
for LN according to the institutional practices using MPA (MMF or entericcoated MPA sodium) or low-dose CYC in addition to corticosteroids.
5. If the subject is on cholesterol-lowering agents, the dose must be stable
for at least 7 days prior to Randomization.
6. Subjects must be treated with anti-malarials (e.g., hydroxychloroquine),
unless contra-indicated, and the dose must be stable for at least 10 days prior
to Randomization.
7. Able to provide signed informed consent.
Exclusion Criteria
Subjects meeting any of the following criteria are not eligible for inclusion
in this study.
1. Severe renal impairment as defined by i.) Stage 4 CKD, or ii.) presence of
oliguria (defined as a documented urine volume < 400 mL/24 hrs), or iii.)
ESRD requiring dialysis or transplantation
2. Known intolerance/hypersensitivity to MPA (MMF or enteric-coated
MPA sodium), or oral corticosteroids, or any component of the study
treatment
3. Subjects having received any other biologic immunomodulatory therapy
within 6 months prior to Screening, excluding belimumab where 3 months
are acceptable
4. Previous exposure to secukinumab (AIN457) or any other biologic drug
targeting IL-17 or the IL-17 receptor
5. Subjects having received any investigational drug within 1 month or five
times the half-life, whichever is longer
6. Receipt of more than 3000 mg i.v. pulse methylprednisolone (cumulative
dose) within the 12 weeks prior to Baseline
7. Treatment with a systemic calcineurin inhibitor (e.g., cyclosporine,
tacrolimus) within 12 weeks prior to Baseline
8. CYC use (i.v. or oral) within the month prior to Baseline
9. Subjects requiring dialysis within the previous 12 months before
Screening
10. History of renal transplant
11. Any severe progressive or uncontrolled concurrent medical condition,
including recent severe thromboembolic events, that, in the opinion of the
principal investigator, renders the subject unsuitable for the trial
12. Active ongoing inflammatory diseases that might confound the
evaluation of the benefit of secukinumab therapy, including inflammatory
bowel disease
13. Presence of investigator-identified significant medical problems which
at the investigator’s discretion will prevent the subject from participating in
the study, including but not limited to the following: myocarditis,
pericarditis, poorly controlled seizure disorder, acute confusional state,
depression, severe manifestations of neuropsychiatric SLE (NPSLE)
14. Chest X-ray, computerized tomography (CT) scan, or MRI with evidence
of ongoing infectious or malignant process, obtained within 12 weeks prior
to Randomization and evaluated by a qualified physician
15. History of chronic, recurrent systemic infections, active tuberculosis
infection, or active systemic infections during the last two weeks (exception:
common cold) prior to Randomization
16. Known infection with human immunodeficiency virus (HIV), hepatitis
B or hepatitis C at Screening or Randomization
17. History of lymphoproliferative disease or any known malignancy or
history of malignancy of any organ system treated or untreated within the
past 5 years, regardless of whether there is evidence of local recurrence or
metastases (except for skin Bowen’s disease or basal cell carcinoma or
actinic keratoses that have been treated with no evidence of recurrence in the
past 12 weeks, carcinoma in situ of the cervix or non-invasive malignant
colon polyps that have been removed)
18. Any of the following abnormal laboratory values on Screening
evaluations as reported by Central Laboratory :
· Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or
amylase > 2.5xULN
· Hemoglobin <8g/dL
· Neutrophils <1.0 x 109/L
· Platelet count <50 x 109/L
19. Inability or unwillingness to undergo repeated venipuncture (e.g.,
because of poor tolerability or lack of venous access)
20. History or evidence of ongoing alcohol or drug abuse, within the last six
months before Randomization
21. Pregnant or lactating women
22. 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)
in this study.
1. Severe renal impairment as defined by i.) Stage 4 CKD, or ii.) presence of
oliguria (defined as a documented urine volume < 400 mL/24 hrs), or iii.)
ESRD requiring dialysis or transplantation
2. Known intolerance/hypersensitivity to MPA (MMF or enteric-coated
MPA sodium), or oral corticosteroids, or any component of the study
treatment
3. Subjects having received any other biologic immunomodulatory therapy
within 6 months prior to Screening, excluding belimumab where 3 months
are acceptable
4. Previous exposure to secukinumab (AIN457) or any other biologic drug
targeting IL-17 or the IL-17 receptor
5. Subjects having received any investigational drug within 1 month or five
times the half-life, whichever is longer
6. Receipt of more than 3000 mg i.v. pulse methylprednisolone (cumulative
dose) within the 12 weeks prior to Baseline
7. Treatment with a systemic calcineurin inhibitor (e.g., cyclosporine,
tacrolimus) within 12 weeks prior to Baseline
8. CYC use (i.v. or oral) within the month prior to Baseline
9. Subjects requiring dialysis within the previous 12 months before
Screening
10. History of renal transplant
11. Any severe progressive or uncontrolled concurrent medical condition,
including recent severe thromboembolic events, that, in the opinion of the
principal investigator, renders the subject unsuitable for the trial
12. Active ongoing inflammatory diseases that might confound the
evaluation of the benefit of secukinumab therapy, including inflammatory
bowel disease
13. Presence of investigator-identified significant medical problems which
at the investigator’s discretion will prevent the subject from participating in
the study, including but not limited to the following: myocarditis,
pericarditis, poorly controlled seizure disorder, acute confusional state,
depression, severe manifestations of neuropsychiatric SLE (NPSLE)
14. Chest X-ray, computerized tomography (CT) scan, or MRI with evidence
of ongoing infectious or malignant process, obtained within 12 weeks prior
to Randomization and evaluated by a qualified physician
15. History of chronic, recurrent systemic infections, active tuberculosis
infection, or active systemic infections during the last two weeks (exception:
common cold) prior to Randomization
16. Known infection with human immunodeficiency virus (HIV), hepatitis
B or hepatitis C at Screening or Randomization
17. History of lymphoproliferative disease or any known malignancy or
history of malignancy of any organ system treated or untreated within the
past 5 years, regardless of whether there is evidence of local recurrence or
metastases (except for skin Bowen’s disease or basal cell carcinoma or
actinic keratoses that have been treated with no evidence of recurrence in the
past 12 weeks, carcinoma in situ of the cervix or non-invasive malignant
colon polyps that have been removed)
18. Any of the following abnormal laboratory values on Screening
evaluations as reported by Central Laboratory :
· Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or
amylase > 2.5xULN
· Hemoglobin <8g/dL
· Neutrophils <1.0 x 109/L
· Platelet count <50 x 109/L
19. Inability or unwillingness to undergo repeated venipuncture (e.g.,
because of poor tolerability or lack of venous access)
20. History or evidence of ongoing alcohol or drug abuse, within the last six
months before Randomization
21. Pregnant or lactating women
22. 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)
The Estimated Number of Participants
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Taiwan
16 participants
-
Global
400 participants
