Lupus NephritisPhase 3SELUNENCT04181762
Study of Safety, Efficacy and Tolerability of Secukinumab Versus Placebo, in Combination With SoC Therapy, in Patients With Active Lupus Nephritis
A Phase 3 study testing secukinumab in people with Lupus Nephritis, run by Novartis Pharmaceuticals at 105 sites in 34 countries.
Trial summary
This was a pivotal, randomized, double-blind, placebo-controlled trial evaluating at Week 52 the efficacy and safety of secukinumab versus placebo in patients with active lupus nephritis (ISN/RPS Class III or IV, with or without co-existing class V features) also receiving background standard of care therapy (SoC). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Lupus Nephritis
- What is being tested?
- secukinumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 275 participants
- Where
- 105 sitesin 34 countries
- Study dates
- 7 Jul 2020to 13 Sep 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult male and female subjects aged 18 - 75 years old at the time of Baseline.
- 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) (Tan et al 1982) revised by (Hochberg 1997). [NOTE: The 4 criteria did not have to be present at the time of Screening], OR
- LN as the sole clinical criterion in the presence of ANA or anti-dsDNA antibodies.
- 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)]; patients are permitted to have co-existing Class V. If no biopsy was performed within 6 months of screening, a biopsy was to be performed during the Screening period
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- UPCR ≥ 1 mg/mg at Screening.
- eGFR > 30 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).
- Active urinary sediment (presence of cellular casts (RBC or WBC casts)) or hematuria (> 5 RBC per high power field or above the laboratory reference range).
- Subjects must have currently been on MPA, or willing to initiate SoC induction therapy for LN according to the institutional practices using MPA or low-dose CYC in addition to corticosteroids. For guidance, see published guidelines such as by (Bertsias et al 2012, Hahn et al 2012).
- Subjects must had been treated with anti-malarials (e.g. hydroxychloroquine), unless contra-indicated, and the dose had been stable for at least 10 days prior to Randomization.
- Able to provide signed informed consent.
Who cannot join
- Severe renal impairment as defined by i.) Stage 4 CKD, or ii.) presence of oliguria (defined as a documented urine volume < 400 mL/24 h), or iii.) ESRD required dialysis or transplantation.
- Known intolerance/hypersensitivity to MPA, or oral corticosteroids, or any component of the study drug(s).
- Subjects received any other biologic immunomodulatory therapy within 6 months prior to Screening, excluding belimumab where 3 months were acceptable.
- Previous exposure to secukinumab (AIN457) or any other biologic drug targeting IL-17 or the IL-17 receptor.
- Subjects received any investigational drug within 1 month or five times the half-life of enrollment, whichever was longer.
- Receipt of more than 3000 mg i.v. pulse methylprednisolone (cumulative dose) within the 12 weeks prior to Baseline.
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- Treatment with a systemic calcineurin inhibitor (e.g. cyclosporine, tacrolimus) within 12 weeks prior to Baseline
- CYC use (i.v. or oral) within the month prior to Baseline.
- Subjects requiring dialysis within the previous 12 months before Screening.
- History of renal transplant.
- 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.
- Active ongoing inflammatory diseases that might confound the evaluation of the benefit of secukinumab therapy, including inflammatory bowel disease.
- Presence of investigator-identified significant medical problems which at the investigator's discretion would prevent the subject from participating in the study, included but not limited to the following: myocarditis, pericarditis, poorly controlled seizure disorder, acute confusional state, depression, severe manifestations of neuropsychiatric SLE (NPSLE).
- Chest X-ray, computerized tomography (CT) scan, or MRI with evidence of ongoing infectious or malignant process, obtained within 3 months preceding the Screening visit and evaluated by a qualified physician.
- History of chronic, recurrent systemic infections, active tuberculosis infection, or active systemic infections during the last two weeks (exception: common cold) prior to Randomization.
- Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C at Screening or Randomization.
- 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 was evidence of local recurrence or metastases (except for skin Bowen's disease or basal cell carcinoma or actinic keratoses that had 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 had been removed).
- 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
- 21. Pregnant or lactating women. 22. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they were 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). Of note: the highly effective methods of contraception were mandated due to SoC medications used as per protocol (MPA and CYC).
- In case local regulations deviated from the contraception methods listed above, local regulations applied and were described in the informed consent form (ICF).
- If stricter female or male contraception requirements were specified in the country-specific label for induction and maintenance standard of care medications, they had to be followed.
- Note: Women were considered post-menopausal and not of childbearing potential if they had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of vasomotor symptoms) or had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks prior to enrollment. In the case of oophorectomy alone, only when the reproductive status of the woman had been confirmed by follow-up hormone level assessment was she considered not of childbearing potential.
Trial locations and contacts
105 sites in 34 countries.
105 sites in 34 countries
China13 sites
Novartis Investigative Site
Beijing, 100034
Novartis Investigative Site
Beijing, 100730
Novartis Investigative Site
Binzhou, Shandong, 256603
Novartis Investigative Site
Changsha, Hunan, 410008
Novartis Investigative Site
Chengdu, Sichuan, 610072
Novartis Investigative Site
Chongqing, 400037
Novartis Investigative Site
Guangzhou, 510280
Novartis Investigative Site
Nanchang, Jiangxi, 330006
Novartis Investigative Site
Nanning, Guangxi, 530021
Novartis Investigative Site
Shanghai, 200025
Novartis Investigative Site
Shanghai, 200040
Novartis Investigative Site
Shijiazhuang, Hebei, 050000
Novartis Investigative Site
Wuhan, 430022
United States8 sites
Piedmont Heart Institute
Atlanta, Georgia, 30309
Arthritis and Rheum Dise Spec
Aventura, Florida, 33180
University Of Alabama
Birmingham, Alabama, 35294
Beth Israel Deaconess Hospital
Boston, Massachusetts, 02215
Kaiser Permanente Fontana
Fontana, California, 92335
Ahmed Arif Medical Research Center
Grand Blanc, Michigan, 48439
University of California LA
Los Angeles, California, 90095
Integral Rheumatology and Immunology Specialists IRIS
Plantation, Florida, 33324
Brazil7 sites
Novartis Investigative Site
Fortaleza, Ceará, 60430 370
Novartis Investigative Site
Joinville, Santa Catarina, 893227-680
Novartis Investigative Site
Porto Alegre, Rio Grande do Sul, 90020-090
Novartis Investigative Site
Santo André, São Paulo, 09090-790
Novartis Investigative Site
São José do Rio Preto, 15090 000
Novartis Investigative Site
São Paulo, São Paulo, 04038-002
Novartis Investigative Site
São Paulo, São Paulo, 05403 000
Japan5 sites
Novartis Investigative Site
Chūō, Yamanashi, 409-3898
Novartis Investigative Site
Kitakyushu, Fukuoka, 807-8556
Novartis Investigative Site
Kurashiki, Okayama-ken, 701-0192
Novartis Investigative Site
Sendai, Miyagi, 980 8574
Novartis Investigative Site
Toyoake, Aichi-ken, 470 1192
Romania5 sites
Novartis Investigative Site
Bucharest, 010 731
Novartis Investigative Site
Bucharest, 011172
Novartis Investigative Site
Bucharest, 022328
Novartis Investigative Site
Oradea, Jud Bihor, 410619
Novartis Investigative Site
Râmnicu Vâlcea, Vâlcea County, 240672
Russia5 sites
Novartis Investigative Site
Kazan', 420012
Novartis Investigative Site
Kemerovo, 650070
Novartis Investigative Site
Rostov-on-Don, 344022
Novartis Investigative Site
Saint Petersburg, 197022
Novartis Investigative Site
Yaroslavl, 150062
Chile4 sites
Novartis Investigative Site
Concepción, 6740
Novartis Investigative Site
Santiago, RM, 7500588
Novartis Investigative Site
Santiago, 7500710
Novartis Investigative Site
Valdivia, Los Ríos Region, 5100238
Colombia4 sites
Novartis Investigative Site
Barranquilla, 080020
Novartis Investigative Site
Cali, 760012
Novartis Investigative Site
Cundinamarca, 111121
Novartis Investigative Site
Medellín, Antioquia, 050001
Mexico4 sites
Novartis Investigative Site
Mérida, Yucatán, 97070
Novartis Investigative Site
Mexicali, Baja California Norte, 21200
Novartis Investigative Site
México, 06726
Novartis Investigative Site
Mexico City, Mexico CP, 14080
Philippines4 sites
Novartis Investigative Site
Iloilo City, 5000
Novartis Investigative Site
Lipa City, Batangas, 4217
Novartis Investigative Site
Manila, 1008
Novartis Investigative Site
Quezon, 1102
Portugal4 sites
Novartis Investigative Site
Coimbra, 3000 075
Novartis Investigative Site
Guimarães, 4835-044
Novartis Investigative Site
Lisbon, 1069 166
Novartis Investigative Site
Porto, 4099-001
Taiwan4 sites
Novartis Investigative Site
Kaohsiung City, 81346
Novartis Investigative Site
Taichung, 40447
Novartis Investigative Site
Taichung, 407219
Novartis Investigative Site
Taoyuan, 33305
Argentina3 sites
Novartis Investigative Site
Caba, Buenos Aires, C1280AEB
Novartis Investigative Site
Ciudad Autonoma de Bs As, Buenos Aires, C1015ABO
Novartis Investigative Site
Córdoba, X5016JDA
Czechia3 sites
Novartis Investigative Site
Prague, 128 50
Novartis Investigative Site
Prague, 12808
Novartis Investigative Site
Prague, 150 06
Guatemala3 sites
Novartis Investigative Site
Guatemala City, 01010
Novartis Investigative Site
Guatemala City, 01011
Novartis Investigative Site
Quetzaltenango, 9001
Spain3 sites
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Santiago de Compostela, Galicia, 15706
Novartis Investigative Site
Vigo, Pontevedra, 36200
Turkey (Türkiye)3 sites
Novartis Investigative Site
Bakırkoy Istanbul, 34147
Novartis Investigative Site
Istanbul, 34093
Novartis Investigative Site
Istanbul, 35100
Vietnam3 sites
Novartis Investigative Site
Hanoi, 100000
Novartis Investigative Site
Ho Chi Minh City, VNM, 700000
Novartis Investigative Site
Ho Chi Minh City, 700000
Greece2 sites
Novartis Investigative Site
Athens, 115 27
Novartis Investigative Site
Thessaloniki, GR-54642
India2 sites
Novartis Investigative Site
New Delhi, National Capital Territory of Delhi, 110 017
Novartis Investigative Site
New Delhi, National Capital Territory of Delhi, 110 060
South Korea2 sites
Novartis Investigative Site
Seoul, Seocho Gu, 06591
Novartis Investigative Site
Seoul, 04763
Thailand2 sites
Novartis Investigative Site
Bangkok, 10400
Novartis Investigative Site
Bangkok, 10700
About this study
Official title: A Two-year, Phase III Randomized, Double-blind, Parallel-group, Placebo-controlled 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
This was a pivotal, randomized, double-blind, placebo-controlled trial evaluating at Week 52 the efficacy and safety of secukinumab versus placebo in patients with active lupus nephritis (ISN/RPS Class III or IV, with or without co-existing class V features) also receiving background standard of care therapy (SoC).
Read the detailed description
The study consisted of the following parts:
- Screening (up to 42 days/6 weeks)
- Run-in period (optional): For subjects who received Mycophenolic acid (MPA) as SoC induction therapy as per investigator's decision and who were not already on MPA at Screening, MPA dosing was initiated during a run-in period before Randomization (for up to 4 weeks prior to the first dose of secukinumab)
- Treatment Period: Duration of 104 weeks of treatment with secukinumab/placebo in addition to SoC treatment (with last dose given at Week 100)
- Secukinumab dosing was started with initial dosing of 300 mg s.c. injections at Baseline, Weeks 1, 2, 3, and 4, followed by dosing every 4 weeks
- Follow-up period: Duration of 8 weeks (last visit performed 12 weeks after last dose of study medication) for all except for subjects entering extension study CAIN457Q12301E1 (NCT05232864).
A total of 275 subjects were enrolled and were randomized to secukinumab 300 mg (n = 137) or placebo (n = 138) until study termination. Recruitment in this study was stopped on 26-May-2023. The CAIN457Q12301 study was terminated early by Novartis due to futile results from interim analysis 1 (IA1). There was no safety related reasons for early termination or concerns for the subjects in the study. The decision was made to terminate both the core and the related extension study in view of treatment futility of the core study.
- Conditions
- Lupus Nephritis
- Being tested
- secukinumab, Placebo
- Keywords
- Systemic Lupus Erythematosus (SLE), Lupus Nephritis (LN), secukinumab, renal biopsy, estimated Glomerular Filtration Rate (eGFR), Urine Protein-to-Creatinine Ratio (UPCR), Standard of Care (SoC) background therapy
- Medical subject headings
- Lupus Nephritis, Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
secukinumabDrug
Also called AIN457
STUDY DRUG
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| secukinumab | Experimental | A blinded, weekly, subcutaneous (s.c.) secukinumab 300 mg loading regimen was administered for the first 4 weeks followed by a monthly maintenance dose in all randomized subjects thereafter. Receives: Drug: secukinumab |
| placebo | Placebo comparator | A blinded, weekly, subcutaneous (s.c.) matching placebo loading regimen was administered for the first 4 weeks followed by a monthly maintenance dose in all randomized subjects thereafter. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Achieving Complete Renal Response (CRR) at Week 52
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
- No treatment discontinuation before Week 52
- The subject did not receive more than 10 mg/day prednisone or equivalent for >= 3 consecutive days or for >= 7 days in total during Week 44 through Week 52.
Non-responder imputation (NRI) was used for participants who did not have the required data to compute responses at Week 52 or who had discontinued study treatment before Week 52. A logistic regression model was used for the analysis of this endpoint.
Measured: Baseline, Week 52
Secondary outcomes (13)
Change From Baseline in 24-hour Urine Protein-to Creatinine Ratio (UPCR)
Urine Protein-to-Creatinine Ratio (UPCR) was determined by a central laboratory by dividing the protein concentration by the creatinine concentration as measured in the urine collected (24-hour urine collection sample).
Measured: Baseline, Week 52
Percentage of Participants Achieving Partial Renal Response (PRR) at Week 52
Partial Renal Response (PRR) is a composite endpoint defined as:
- >= 50% reduction in 24-hour Urine-to-Protein Creatinine Ratio (UPCR) to sub-nephrotic levels (=< 3 mg/mg) and
- Estimated Glomerular Filtration Rate (eGFR) >= 60 mL/min/1.73 m^2 or no less than 85% of Baseline
Measured: Baseline, Week 52
Average Daily Dose of Oral Corticosteroids
Average daily dose of oral corticosteroids doses was used to assess efficacy of secukinumab compared to placebo in the averaged daily dose of oral corticosteroids administered between Week 16 and Week 52.
Measured: Week 16 to Week 52
Percentage of Participants Achieving Partial Renal Response (PRR) at Week 24
Partial Renal Response (PRR) is a composite endpoint defined as:
- >= 50% reduction in 24-hour Urine-to-Protein Creatinine Ratio (UPCR) to sub-nephrotic levels (=< 3 mg/mg) and
- Estimated Glomerular Filtration Rate (eGFR) >= 60 mL/min/1.73 m^2 or no less than 85% of Baseline
Measured: Baseline, Week 24
Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52
Time to achieve Complete Renal Response (CRR) up to week 52 was evaluated by 4-week interval by using Kaplan-Meier estimates. Participants who did not achieve CRR were censored at the date of their last non-missing CRR result (including participants who completed week 52 without achieving CRR).
- Subjects at risk = Subjects who did not achieve CRR and were not censored before or at the start of the specified interval. Participants had an event when achieving CRR.
- Incidence rate (%) = (number of subjects with event/number of subjects at risk) x 100.
Measured: Baseline to Week 52
Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52
Time to achieve Partial Renal Response (PRR) up to week 52 was evaluated by 4-week interval by using Kaplan-Meier estimates. Participants who did not achieve PRR were censored at the date of their last non-missing PRR result (including participants who completed week 52 without achieving PRR). Participants had event when achieving PRR.
- Subjects at risk = Subjects who did not achieve PRR and were not censored before or at the start of the specified interval.
- Incidence rate (%) = (number of subjects with event/ number of subjects at risk) x 100.
Measured: Baseline to Week 52
Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52
Time to achieve first morning void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to week 52 was evaluated by 4-week interval by using Kaplan-Meier estimates. Participants who did not achieve UCPR were censored at the date of their last non-missing UCPR result (including participants who completed week 52 without achieving UCPR). Participants had event when achieving UCPR.
- Subjects at risk = Subjects who did not achieve UCPR and were not censored before or at the start of the specified interval.
- Incidence rate (%) = (number of subjects with event/ number of subjects at risk) x 100.
Measured: Baseline to Week 52
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Mean Change From Baseline up to Week 52
The FACIT-Fatigue is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function over the past week. The purpose of the FACIT-Fatigue in this study was to assess the impact of fatigue on subjects with lupus nephritis (LN). The level of fatigue was measured on a 5-point Likert scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much) based on their experience of fatigue during the past 2 weeks. The scale score is computed by summing the item scores, after reversing those items that are worded in the negative direction. FACIT-Fatigue scale score range from 0 to 52, where higher scores represent less fatigue.
Measured: Baseline, Week 12, Week 24, Week 36, Week 52
Short Form Health Survey (SF-36) Version 2 (Acute Form) Mean Change From Baseline in Physical Component Score (PCS) up to Week 52
The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. The physical health measure includes four scales of physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health (5 items). The mental health measure is composed of vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items). In this trial, SF-36-PCS responder (improvement of >= 2.5 points) were evaluated. Responses to items allow for direct calculation of scale scores, while the physical component summary (PCS) scores are computed from weighted scale scores. For all scales and summary measures, higher scores indicate better health outcomes (PCS scores range 0 to 100).
Measured: Baseline, Week 12, Week 24, Week 36, Week 52
Lupus Quality of Life (LupusQoL) Physical Health Score Mean Change From Baseline up to Week 52
The LupusQoL is a disease-specific, 34-item, self-report questionnaire designed to measure the health-related quality of life (HRQoL) of subjects with SLE within 8 domains (i.e., physical health (8 items), emotional health (6 items), body image (5 items), pain (3 items), planning (3 items), fatigue (4 items), intimate relationships (2 items), and burden to others (3 items)). Responses are based on a 5-point Likert scale where 0 (all of the time) to 4 (never). Each domain of the LupusQoL was scored separately. Transformed scores range from 0 (worst HRQoL) to 100 (best HRQoL).
Measured: Baseline, Week 12, Week 24, Week 36, Week 52
Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs)
The distribution of adverse events was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
Measured: From first dose of study treatment up to approximately 2 years
Percentage of Participants With Complete Renal Response (CRR) at Week 104 Within Those Who Had Achieved CRR at Week 52 in the Secukinumab Group
The percentage of participants with maintained renal response (CRR) at Week 104 in the secukinumab group was evaluated
Measured: Week 52 to Week 104
Percentage of Participants With Improved or Maintained Response (PRR or CRR) at Week 104 in Those Who Had Achieved at Least PRR at Week 52 in the Secukinumab Group
The percentage of participants with improved or maintained renal response (CRR) at Week 104 in the secukinumab group was evaluated
Measured: Week 52 to Week 104
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2019
- Study start7 Jul 2020
- Primary completion13 Sep 2023
- Study completion13 Sep 2023
Why it stopped: Study terminated by sponsor due to futility analysis
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Lupus NephritisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 275 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04181762
- Sponsor's protocol ID
- CAIN457Q12301
- Other IDs
- 2019-003211-57, PACTR202211748997845, 2019
- Acronym
- SELUNE
- Status last verified
- May 2025
- First submitted
- 27 Nov 2019
- Last updated
- 16 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Zhao MH, Cons Molina F, Aroca G, Tektonidou MG, Mathur A, Tangadpalli R, Sun R, Martin R, Pellet P, Ngoc Phuong Huynh T. Secukinumab in active lupus nephritis: results from a phase III randomized, placebo-controlled study (SELUNE) and an open-label extension study. Rheumatology (Oxford). 2026 Jan 8;65(1):keaf536. doi: 10.1093/rheumatology/keaf536.
PubMed 41092316Avasare R, Drexler Y, Caster DJ, Mitrofanova A, Jefferson JA. Management of Lupus Nephritis: New Treatments and Updated Guidelines. Kidney360. 2023 Oct 1;4(10):1503-1511. doi: 10.34067/KID.0000000000000230.
PubMed 37528520
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-year, Phase III Randomized, Double-blind, Parallel-group, Placebo-controlled 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
- ClinicalTrials.gov ID
- NCT04181762
- Acronym / sponsor ID
- SELUNE / CAIN457Q12301
- Conditions
- Lupus Nephritis
- Keywords
- Systemic Lupus Erythematosus (SLE), Lupus Nephritis (LN), secukinumab, renal biopsy, estimated Glomerular Filtration Rate (eGFR), Urine Protein-to-Creatinine Ratio (UPCR), Standard of Care (SoC) background therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated by sponsor due to futility analysis
- Enrolment
- 275 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 7 Jul 2020 (actual)
- Primary completion
- 13 Sep 2023 (actual)
- Study completion
- 13 Sep 2023 (actual)
- First posted
- 29 Nov 2019 (actual)
- Results
- Posted 10 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a pivotal, randomized, double-blind, placebo-controlled trial evaluating at Week 52 the efficacy and safety of secukinumab versus placebo in patients with active lupus nephritis (ISN/RPS Class III or IV, with or without co-existing class V features) also receiving background standard of care therapy (SoC).
Detailed description
The study consisted of the following parts:
- Screening (up to 42 days/6 weeks)
- Run-in period (optional): For subjects who received Mycophenolic acid (MPA) as SoC induction therapy as per investigator's decision and who were not already on MPA at Screening, MPA dosing was initiated during a run-in period before Randomization (for up to 4 weeks prior to the first dose of secukinumab)
- Treatment Period: Duration of 104 weeks of treatment with secukinumab/placebo in addition to SoC treatment (with last dose given at Week 100)
- Secukinumab dosing was started with initial dosing of 300 mg s.c. injections at Baseline, Weeks 1, 2, 3, and 4, followed by dosing every 4 weeks
- Follow-up period: Duration of 8 weeks (last visit performed 12 weeks after last dose of study medication) for all except for subjects entering extension study CAIN457Q12301E1 (NCT05232864).
A total of 275 subjects were enrolled and were randomized to secukinumab 300 mg (n = 137) or placebo (n = 138) until study termination. Recruitment in this study was stopped on 26-May-2023. The CAIN457Q12301 study was terminated early by Novartis due to futile results from interim analysis 1 (IA1). There was no safety related reasons for early termination or concerns for the subjects in the study. The decision was made to terminate both the core and the related extension study in view of treatment futility of the core study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| secukinumab | Experimental | Drug: secukinumabA blinded, weekly, subcutaneous (s.c.) secukinumab 300 mg loading regimen was administered for the first 4 weeks followed by a monthly maintenance dose in all randomized subjects thereafter. |
| placebo | Placebo comparator | Drug: PlaceboA blinded, weekly, subcutaneous (s.c.) matching placebo loading regimen was administered for the first 4 weeks followed by a monthly maintenance dose in all randomized subjects thereafter. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Adult male and female subjects aged 18 - 75 years old at the time of Baseline.
- Confirmed diagnosis of:
- Active lupus nephritis, as defined by meeting the 4 following criteria:
- Subjects must have currently been on MPA, or willing to initiate SoC induction therapy for LN according to the institutional practices using MPA or low-dose CYC in addition to corticosteroids. For guidance, see published guidelines such as by (Bertsias et al 2012, Hahn et al 2012).
- Subjects must had been treated with anti-malarials (e.g. hydroxychloroquine), unless contra-indicated, and the dose had been stable for at least 10 days prior to Randomization.
Key exclusion criteria (26 listed)
- Severe renal impairment as defined by i.) Stage 4 CKD, or ii.) presence of oliguria (defined as a documented urine volume < 400 mL/24 h), or iii.) ESRD required dialysis or transplantation.
- Known intolerance/hypersensitivity to MPA, or oral corticosteroids, or any component of the study drug(s).
- Subjects received any other biologic immunomodulatory therapy within 6 months prior to Screening, excluding belimumab where 3 months were acceptable.
- Previous exposure to secukinumab (AIN457) or any other biologic drug targeting IL-17 or the IL-17 receptor.
- Subjects received any investigational drug within 1 month or five times the half-life of enrollment, whichever was longer.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| secukinumabAlso: AIN457STUDY DRUG | Drug | secukinumab |
| PlaceboPlacebo | Drug | placebo |
Primary outcome
Percentage of Participants Achieving Complete Renal Response (CRR) at Week 52
Time frame: Baseline, Week 52
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 * No treatment discontinuation before Week 52 * The subject did not receive more than 10 mg/day prednisone or equivalent for >= 3 consecutive days or for >= 7 days in total during Week 44 through Week 52. Non-responder imputation (NRI) was used for participants who did not have the required data to compute responses at Week 52 or who had discontinued study treatment before Week 52. A logistic regression model was used for the analysis of this endpoint.
13 secondary outcomes
Change From Baseline in 24-hour Urine Protein-to Creatinine Ratio (UPCR)
Time frame: Baseline, Week 52
Percentage of Participants Achieving Partial Renal Response (PRR) at Week 52
Time frame: Baseline, Week 52
Average Daily Dose of Oral Corticosteroids
Time frame: Week 16 to Week 52
Percentage of Participants Achieving Partial Renal Response (PRR) at Week 24
Time frame: Baseline, Week 24
Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52
Time frame: Baseline to Week 52
Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52
Time frame: Baseline to Week 52
Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52
Time frame: Baseline to Week 52
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Mean Change From Baseline up to Week 52
Time frame: Baseline, Week 12, Week 24, Week 36, Week 52
Short Form Health Survey (SF-36) Version 2 (Acute Form) Mean Change From Baseline in Physical Component Score (PCS) up to Week 52
Time frame: Baseline, Week 12, Week 24, Week 36, Week 52
Lupus Quality of Life (LupusQoL) Physical Health Score Mean Change From Baseline up to Week 52
Time frame: Baseline, Week 12, Week 24, Week 36, Week 52
Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs)
Time frame: From first dose of study treatment up to approximately 2 years
Percentage of Participants With Complete Renal Response (CRR) at Week 104 Within Those Who Had Achieved CRR at Week 52 in the Secukinumab Group
Time frame: Week 52 to Week 104
Percentage of Participants With Improved or Maintained Response (PRR or CRR) at Week 104 in Those Who Had Achieved at Least PRR at Week 52 in the Secukinumab Group
Time frame: Week 52 to Week 104
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41092316Zhao MH, Cons Molina F, Aroca G, Tektonidou MG, Mathur A, Tangadpalli R, Sun R, Martin R, Pellet P, Ngoc Phuong Huynh T. Secukinumab in active lupus nephritis: results from a phase III randomized, placebo-controlled study (SELUNE) and an open-label extension study. Rheumatology (Oxford). 2026 Jan 8;65(1):keaf536. doi: 10.1093/rheumatology/keaf536.
- Derived from this study: PubMed 37528520Avasare R, Drexler Y, Caster DJ, Mitrofanova A, Jefferson JA. Management of Lupus Nephritis: New Treatments and Updated Guidelines. Kidney360. 2023 Oct 1;4(10):1503-1511. doi: 10.34067/KID.0000000000000230.
- A Plain Language Trial Summary is available on www.novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing access to patient-level data and supporting clinical documents from eligible studies with qualified external researchers. Requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to protect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
105 sites in 34 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing secukinumab in people with Lupus Nephritis, run by Novartis Pharmaceuticals at 105 sites in 34 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 105 sites in China, United States, Brazil, Japan, Romania and 29 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Achieving Complete Renal Response (CRR) at Week 52 (time frame: Baseline, Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04181762, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2025.