Study of Safety, Efficacy and Tolerability of Secukinumab Versus Placebo, in Combination With SoC Therapy, in Patients With Active Lupus Nephritis

NCT04181762 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: CAIN457Q123012019-003211-57PACTR202211748997845
• Study Type: interventional
• Target: 275
• Locations: 34 countries
• Sites: 105

Brief 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).

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, Week 52

Secondary Outcomes (13)

• Change From Baseline in 24-hour Urine Protein-to Creatinine Ratio (UPCR)

  Baseline, Week 52

• Percentage of Participants Achieving Partial Renal Response (PRR) at Week 52

  Baseline, Week 52

• Average Daily Dose of Oral Corticosteroids

  Week 16 to Week 52

• Percentage of Participants Achieving Partial Renal Response (PRR) at Week 24

  Baseline, Week 24

• Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52

  Baseline to Week 52

Study Arms (2)

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.

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.

Drug: Placebo

Interventions

secukinumab DRUG

STUDY DRUG

Also known as: AIN457

secukinumab

Placebo DRUG

Placebo

placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (105)

University Of Alabama

Birmingham, Alabama, 35294, United States

Location

Kaiser Permanente Fontana

Fontana, California, 92335, United States

Location

University of California LA

Los Angeles, California, 90095, United States

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Arthritis and Rheum Dise Spec

Aventura, Florida, 33180, United States

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Integral Rheumatology and Immunology Specialists IRIS

Plantation, Florida, 33324, United States

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Piedmont Heart Institute

Atlanta, Georgia, 30309, United States

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Beth Israel Deaconess Hospital

Boston, Massachusetts, 02215, United States

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Ahmed Arif Medical Research Center

Grand Blanc, Michigan, 48439, United States

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Novartis Investigative Site

Caba, Buenos Aires, C1280AEB, Argentina

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Novartis Investigative Site

Ciudad Autonoma de Bs As, Buenos Aires, C1015ABO, Argentina

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Novartis Investigative Site

Córdoba, X5016JDA, Argentina

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Westmead, New South Wales, 2145, Australia

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Fortaleza, Ceará, 60430 370, Brazil

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Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90020-090, Brazil

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Novartis Investigative Site

Joinville, Santa Catarina, 893227-680, Brazil

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Santo André, São Paulo, 09090-790, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 04038-002, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 05403 000, Brazil

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Novartis Investigative Site

São José do Rio Preto, 15090 000, Brazil

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Toronto, Ontario, M5T 2S8, Canada

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Valdivia, Los Ríos Region, 5100238, Chile

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Santiago, RM, 7500588, Chile

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Concepción, 6740, Chile

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Santiago, 7500710, Chile

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Nanning, Guangxi, 530021, China

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Shijiazhuang, Hebei, 050000, China

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Changsha, Hunan, 410008, China

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Nanchang, Jiangxi, 330006, China

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Binzhou, Shandong, 256603, China

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Chengdu, Sichuan, 610072, China

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Beijing, 100034, China

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Beijing, 100730, China

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Chongqing, 400037, China

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Guangzhou, 510280, China

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Shanghai, 200025, China

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Shanghai, 200040, China

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Wuhan, 430022, China

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Medellín, Antioquia, 050001, Colombia

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Barranquilla, 080020, Colombia

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Cali, 760012, Colombia

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Cundinamarca, 111121, Colombia

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Zagreb, 10000, Croatia

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Prague, 128 50, Czechia

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Prague, 12808, Czechia

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Prague, 150 06, Czechia

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Odense C, 5000, Denmark

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Marseille, 13385, France

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Mainz, 55131, Germany

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Athens, 115 27, Greece

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Thessaloniki, GR-54642, Greece

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Guatemala City, 01010, Guatemala

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Guatemala City, 01011, Guatemala

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Quetzaltenango, 9001, Guatemala

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New Delhi, National Capital Territory of Delhi, 110 017, India

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New Delhi, National Capital Territory of Delhi, 110 060, India

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Padua, PD, 35128, Italy

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Toyoake, Aichi-ken, 470 1192, Japan

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Kitakyushu, Fukuoka, 807-8556, Japan

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Sendai, Miyagi, 980 8574, Japan

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Kurashiki, Okayama-ken, 701-0192, Japan

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Chūō, Yamanashi, 409-3898, Japan

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Mexicali, Baja California Norte, 21200, Mexico

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Mexico City, Mexico CP, 14080, Mexico

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Mérida, Yucatán, 97070, Mexico

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México, 06726, Mexico

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Oslo, 0372, Norway

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Santiago de Surco, Lima region, 33, Peru

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Lipa City, Batangas, 4217, Philippines

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Iloilo City, 5000, Philippines

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Manila, 1008, Philippines

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Quezon, 1102, Philippines

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Coimbra, 3000 075, Portugal

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Guimarães, 4835-044, Portugal

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Lisbon, 1069 166, Portugal

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Porto, 4099-001, Portugal

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Oradea, Jud Bihor, 410619, Romania

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Râmnicu Vâlcea, Vâlcea County, 240672, Romania

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Bucharest, 010 731, Romania

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Bucharest, 011172, Romania

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Bucharest, 022328, Romania

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Kazan', 420012, Russia

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Kemerovo, 650070, Russia

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Rostov-on-Don, 344022, Russia

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Saint Petersburg, 197022, Russia

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Yaroslavl, 150062, Russia

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Piešťany, 92101, Slovakia

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Seoul, Seocho Gu, 06591, South Korea

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Seoul, 04763, South Korea

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Barcelona, Catalonia, 08036, Spain

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Santiago de Compostela, Galicia, 15706, Spain

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Vigo, Pontevedra, 36200, Spain

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Stockholm, 17176, Sweden

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Sankt Gallen, 9007, Switzerland

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Kaohsiung City, 81346, Taiwan

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Taichung, 40447, Taiwan

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Taichung, 407219, Taiwan

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Taoyuan District, 33305, Taiwan

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Bangkok, 10400, Thailand

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Bangkok, 10700, Thailand

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Bakırkoy Istanbul, 34147, Turkey (Türkiye)

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Istanbul, 34093, Turkey (Türkiye)

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Istanbul, 35100, Turkey (Türkiye)

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Ho Chi Minh City, VNM, 700000, Vietnam

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Hanoi, 100000, Vietnam

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Novartis Investigative Site

Ho Chi Minh City, 700000, Vietnam

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Related Publications (2)

• 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 phase III, randomised, placebo-controlled study (SELUNE) and open-label extension study. Rheumatology (Oxford). 2025 Oct 15:keaf536. doi: 10.1093/rheumatology/keaf536. Online ahead of print.

  PMID: 41092316 DERIVED

• Avasare 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.

  PMID: 37528520 DERIVED

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Lupus Nephritis; Lupus Erythematosus, Systemic

Interventions

secukinumab

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2019
• First Posted: November 29, 2019
• Study Start: July 7, 2020
• Primary Completion: September 13, 2023
• Study Completion: September 13, 2023
• Last Updated: May 16, 2025
• Results First Posted: October 10, 2024

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

AR (3); DE (1); JP (5); GU (3); CL (4); SL (1); CN (13); FR (1); US (8); KR (2); ME (4); TU (3); IT (1); GR (2); CZ (3); PE (1); DK (1); CO (4); RU (5); CH (1); ES (3); CA (1); NO (1); IN (2); BR (7); TH (2); PT (4); PH (4); AU (1); CR (1); RO (5); SE (1); TW (4); VN (3)