Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04181762




Registration number
NCT04181762
Ethics application status
Date submitted
27/11/2019
Date registered
29/11/2019
Date last updated
10/10/2024

Titles & IDs
Public title
Study of Safety, Efficacy and Tolerability of Secukinumab Versus Placebo, in Combination With SoC Therapy, in Patients With Active Lupus Nephritis
Scientific 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
Secondary ID [1] 0 0
2019-003211-57
Secondary ID [2] 0 0
CAIN457Q12301
Universal Trial Number (UTN)
Trial acronym
SELUNE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lupus Nephritis 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - secukinumab
Treatment: Drugs - Placebo

Experimental: secukinumab - 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.

Placebo comparator: placebo - 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.


Treatment: Drugs: secukinumab
STUDY DRUG

Treatment: Drugs: Placebo
Placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Achieving Complete Renal Response (CRR) at Week 52
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [1] 0 0
Change From Baseline in 24-hour Urine Protein-to Creatinine Ratio (UPCR)
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [2] 0 0
Percentage of Participants Achieving Partial Renal Response (PRR) at Week 52
Timepoint [2] 0 0
Baseline, Week 52
Secondary outcome [3] 0 0
Average Daily Dose of Oral Corticosteroids
Timepoint [3] 0 0
Week 16 to Week 52
Secondary outcome [4] 0 0
Percentage of Participants Achieving Partial Renal Response (PRR) at Week 24
Timepoint [4] 0 0
Baseline, Week 24
Secondary outcome [5] 0 0
Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52
Timepoint [5] 0 0
Baseline to Week 52
Secondary outcome [6] 0 0
Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52
Timepoint [6] 0 0
Baseline to Week 52
Secondary outcome [7] 0 0
Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52
Timepoint [7] 0 0
Baseline to Week 52
Secondary outcome [8] 0 0
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Mean Change From Baseline up to Week 52
Timepoint [8] 0 0
Baseline, Week 12, Week 24, Week 36, Week 52
Secondary outcome [9] 0 0
Short Form Health Survey (SF-36) Version 2 (Acute Form) Mean Change From Baseline in Physical Component Score (PCS) up to Week 52
Timepoint [9] 0 0
Baseline, Week 12, Week 24, Week 36, Week 52
Secondary outcome [10] 0 0
Lupus Quality of Life (LupusQoL) Physical Health Score Mean Change From Baseline up to Week 52
Timepoint [10] 0 0
Baseline, Week 12, Week 24, Week 36, Week 52
Secondary outcome [11] 0 0
Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs)
Timepoint [11] 0 0
From first dose of study treatment up to approximately 2 years
Secondary outcome [12] 0 0
Percentage of Participants With Complete Renal Response (CRR) at Week 104 Within Those Who Had Achieved CRR at Week 52 in the Secukinumab Group
Timepoint [12] 0 0
Week 52 to Week 104
Secondary outcome [13] 0 0
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
Timepoint [13] 0 0
Week 52 to Week 104

Eligibility
Key inclusion criteria
Key inclusion 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) (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.
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)]; 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).
4. 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).
5. 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.
6. Able to provide signed informed consent.

Key
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

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 h), or iii.) ESRD required dialysis or transplantation.
2. Known intolerance/hypersensitivity to MPA, or oral corticosteroids, or any component of the study drug(s).
3. Subjects received any other biologic immunomodulatory therapy within 6 months prior to Screening, excluding belimumab where 3 months were acceptable.
4. Previous exposure to secukinumab (AIN457) or any other biologic drug targeting IL-17 or the IL-17 receptor.
5. Subjects received any investigational drug within 1 month or five times the half-life of enrollment, whichever was 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 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).
14. 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.
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 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).
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

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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/07/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/09/2023
Sample size
Target
Accrual to date
Final
275
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Novartis Investigative Site - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
Argentina
State/province [7] 0 0
Buenos Aires
Country [8] 0 0
Argentina
State/province [8] 0 0
Cordoba
Country [9] 0 0
Brazil
State/province [9] 0 0
CE
Country [10] 0 0
Brazil
State/province [10] 0 0
RS
Country [11] 0 0
Brazil
State/province [11] 0 0
Santa Catarina
Country [12] 0 0
Brazil
State/province [12] 0 0
SP
Country [13] 0 0
Brazil
State/province [13] 0 0
Sao Jose do Rio Preto
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Chile
State/province [15] 0 0
Los Rios
Country [16] 0 0
Chile
State/province [16] 0 0
RM
Country [17] 0 0
Chile
State/province [17] 0 0
Concepcion
Country [18] 0 0
Chile
State/province [18] 0 0
Santiago
Country [19] 0 0
China
State/province [19] 0 0
Guangxi
Country [20] 0 0
China
State/province [20] 0 0
Hebei
Country [21] 0 0
China
State/province [21] 0 0
Hunan
Country [22] 0 0
China
State/province [22] 0 0
Jiangxi
Country [23] 0 0
China
State/province [23] 0 0
Shandong
Country [24] 0 0
China
State/province [24] 0 0
Sichuan
Country [25] 0 0
China
State/province [25] 0 0
Beijing
Country [26] 0 0
China
State/province [26] 0 0
Chongqing
Country [27] 0 0
China
State/province [27] 0 0
Guangzhou
Country [28] 0 0
China
State/province [28] 0 0
Shanghai
Country [29] 0 0
China
State/province [29] 0 0
Wuhan
Country [30] 0 0
Colombia
State/province [30] 0 0
Antioquia
Country [31] 0 0
Colombia
State/province [31] 0 0
Barranquilla
Country [32] 0 0
Colombia
State/province [32] 0 0
Cali
Country [33] 0 0
Colombia
State/province [33] 0 0
Cundinamarca
Country [34] 0 0
Croatia
State/province [34] 0 0
Zagreb
Country [35] 0 0
Czechia
State/province [35] 0 0
Praha 2
Country [36] 0 0
Czechia
State/province [36] 0 0
Praha 5
Country [37] 0 0
Czechia
State/province [37] 0 0
Praha
Country [38] 0 0
Denmark
State/province [38] 0 0
Odense C
Country [39] 0 0
France
State/province [39] 0 0
Marseille
Country [40] 0 0
Germany
State/province [40] 0 0
Mainz
Country [41] 0 0
Greece
State/province [41] 0 0
Athens
Country [42] 0 0
Greece
State/province [42] 0 0
Thessaloniki
Country [43] 0 0
Guatemala
State/province [43] 0 0
Guatemala City
Country [44] 0 0
Guatemala
State/province [44] 0 0
Guatemala
Country [45] 0 0
Guatemala
State/province [45] 0 0
Quetzaltenango
Country [46] 0 0
India
State/province [46] 0 0
Delhi
Country [47] 0 0
Italy
State/province [47] 0 0
PD
Country [48] 0 0
Japan
State/province [48] 0 0
Aichi
Country [49] 0 0
Japan
State/province [49] 0 0
Fukuoka
Country [50] 0 0
Japan
State/province [50] 0 0
Miyagi
Country [51] 0 0
Japan
State/province [51] 0 0
Okayama
Country [52] 0 0
Japan
State/province [52] 0 0
Yamanashi
Country [53] 0 0
Korea, Republic of
State/province [53] 0 0
Seocho Gu
Country [54] 0 0
Korea, Republic of
State/province [54] 0 0
Seoul
Country [55] 0 0
Mexico
State/province [55] 0 0
Baja California Norte
Country [56] 0 0
Mexico
State/province [56] 0 0
Mexico CP
Country [57] 0 0
Mexico
State/province [57] 0 0
Yucatan
Country [58] 0 0
Mexico
State/province [58] 0 0
Mexico
Country [59] 0 0
Norway
State/province [59] 0 0
Oslo
Country [60] 0 0
Peru
State/province [60] 0 0
Lima
Country [61] 0 0
Philippines
State/province [61] 0 0
Batangas
Country [62] 0 0
Philippines
State/province [62] 0 0
Iloilo
Country [63] 0 0
Philippines
State/province [63] 0 0
Manila
Country [64] 0 0
Philippines
State/province [64] 0 0
Quezon
Country [65] 0 0
Portugal
State/province [65] 0 0
Coimbra
Country [66] 0 0
Portugal
State/province [66] 0 0
Guimaraes
Country [67] 0 0
Portugal
State/province [67] 0 0
Lisboa
Country [68] 0 0
Portugal
State/province [68] 0 0
Porto
Country [69] 0 0
Romania
State/province [69] 0 0
Jud Bihor
Country [70] 0 0
Romania
State/province [70] 0 0
Valcea
Country [71] 0 0
Romania
State/province [71] 0 0
Bucharest
Country [72] 0 0
Romania
State/province [72] 0 0
Bucuresti
Country [73] 0 0
Russian Federation
State/province [73] 0 0
Kazan
Country [74] 0 0
Russian Federation
State/province [74] 0 0
Kemerovo
Country [75] 0 0
Russian Federation
State/province [75] 0 0
Rostov On Don
Country [76] 0 0
Russian Federation
State/province [76] 0 0
Saint Petersburg
Country [77] 0 0
Russian Federation
State/province [77] 0 0
Yaroslavl
Country [78] 0 0
Slovakia
State/province [78] 0 0
Piestany
Country [79] 0 0
Spain
State/province [79] 0 0
Catalunya
Country [80] 0 0
Spain
State/province [80] 0 0
Galicia
Country [81] 0 0
Spain
State/province [81] 0 0
Pontevedra
Country [82] 0 0
Sweden
State/province [82] 0 0
Stockholm
Country [83] 0 0
Switzerland
State/province [83] 0 0
St Gallen
Country [84] 0 0
Taiwan
State/province [84] 0 0
Kaohsiung
Country [85] 0 0
Taiwan
State/province [85] 0 0
Taichung
Country [86] 0 0
Taiwan
State/province [86] 0 0
Taoyuan
Country [87] 0 0
Thailand
State/province [87] 0 0
Bangkok
Country [88] 0 0
Turkey
State/province [88] 0 0
Bakirkoy Istanbul
Country [89] 0 0
Turkey
State/province [89] 0 0
Istanbul
Country [90] 0 0
Vietnam
State/province [90] 0 0
VNM
Country [91] 0 0
Vietnam
State/province [91] 0 0
Hanoi
Country [92] 0 0
Vietnam
State/province [92] 0 0
Ho Chi Minh

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT04181762
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04181762