Safety, Efficacy and Tolerability of Ianalumab Versus Placebo, Combination With SoC Therapy, in Participants With Active Lupus Nephritis

Lupus Nephritis Clinical Trial

— SIRIUS-LN  

Official title:

A Randomized, Double-blind, Parallel Group, Placebo-controlled, Multicenter Phase 3 Trial to Evaluate Efficacy, Safety and Tolerability of Ianalumab on Top of Standard-of-care Therapy in Participants With Active Lupus Nephritis (SIRIUS-LN).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05126277
• Other study ID #: CVAY736K12301
• Secondary ID: 2020-005830-14
• Status: Recruiting
• Phase: Phase 3
• Start date: July 14, 2022
• Est. completion date: July 15, 2030

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial will evaluate efficacy, safety, and tolerability of subcutaneous (s.c.) ianalumab given every 4 weeks (q4w) or every 12 weeks (q12w) compared to placebo, in combination with SoC, in adult participants with active LN

Description:

This trial will evaluate the efficacy, safety, and tolerability of subcutaneous (s.c.) ianalumab given every 4 weeks (q4w) or ianalumab given every 12 weeks (q12w) compared to placebo, in combination with SoC, in adult participants with active LN (ISN/RPS class III, IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous). using the 2003 International Society for Nephrology (ISN)/Renal Pathology Society (RPS) criteria).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 420
• Est. completion date: July 15, 2030
• Est. primary completion date: March 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

• Adult male and female participants aged 18 years or older at the time of screening

• Weigh at least 35 kg at screening

• Have a confirmed clinical diagnosis of SLE according to European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) Systemic Lupus Erythematosus (SLE) classification criteria

• Have a positive anti-nuclear antibody (ANA) test result; ANA titer = 1:80 at screening visit based on central or local laboratory result

• Active LN at screening, as defined by meeting the 3 following criteria:

• Renal biopsy within 6 months prior to screening period indicating ISN/RPS class III or IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous LN. If no biopsy was performed within 6 months prior to screening period, a biopsy will need to be performed during the screening period after having met all other inclusion/exclusion criteria.

• UPCR = 1.0 g/g on 24h urine collection at Screening

• eGFR = 25mL/min/1.73 m2. Participants with eGFR < 30 mL/min/1.73 m2 require renal biopsy during the screening period showing sclerosis in = 50% of glomeruli

• Newly diagnosed participants as well as pre-treated LN participants (including refractory cases) can be included, as long as they are currently on, or willing to initiate SoC induction therapy for LN using MPA

• Induction therapy, as defined by treatment including both high dose corticosteroids and MPA, should be initiated prior to or on day of randomization

• Anti-malarial treatment at stable dosing prior to randomization is strongly recommended, in the absence of contraindications

• Participants on azathioprine treatment at Screening must be switched to MPA prior to randomization

• Receipt of at least one dose of pulse methylprednisolone i.v. (250 - 1000 mg per day up to 3000 mg cumulative dose) or equivalent for treatment of current episode of active LN within 60 days prior randomization. Participant who cannot take the pulse i.v. corticosteroid therapy should directly start on 0.8-1.0 mg/day (max 80mg/day) oral predniso(lo)ne.

• Able to communicate well with the Investigator to understand and comply with the requirements of the study

Exclusion Criteria:

Participants meeting any of the following criteria are not eligible for inclusion in this study:

• Severe renal impairment as defined by i.) presence of oliguria (defined as a documented urine volume <400 mL/24 hrs) or ii.) End-Stage Renal Disease (ESRD) requiring dialysis or transplantation

• Sclerosis in > 50% of glomeruli on renal biopsy

• Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected pharmacodynamic effect has returned to baseline. Use of certain Traditional Chinese Medicines

• Prior use of ianalumab (ever); or prior use other B cell depleting therapy within 36 weeks prior to randomization or if therapy was administered < 36 weeks prior to randomization, B cell count less than the lower limit of normal or patient's own baseline value prior to having received an earlier B cell-depleting therapy

• Prior treatment with any of the following within 12 weeks prior to randomization

• Belimumab, telitacicept, abatacept, TNF-a mAb, immunoglobulins (i.v./s.c.) plasmapheresis

• Any other immuno-suppressants (i.v. or oral cyclophosphamide, calcineurin inhibitors, JAK inhibitors or other kinase inhibitors)

• Thalidomide treatment and/or methotrexate

• Combination of DMARDs

• Imidazole derivative (e.g., azathioprine, mizoribine) must be discontinued prior to starting treatment with MPA

• Receipt of more than 3000 mg i.v. pulse methylprednisolone (cumulative dose) within 12 weeks prior to randomization

• History of major organ transplant or hematopoietic stem cell/bone marrow transplant or are due to receive transplantation

• Any one of the following laboratory values at screening:

• Hemoglobin levels < 8.0 g/dL (< 5 mmol/L), or < 7.0 g/dL (< 4.3 mmol/L) if related to participant's SLE such as in active hemolytic anaemia

• Platelet count < 25 x 1000/µL

• Absolute neutrophil count (ANC) < 0.8 x 1000/µL

• Active viral, bacterial or other infections requiring intravenous or intramuscular treatment for clinically significant infection or history of recurrent clinically significant infection which in the opinion of the investigator will place the participant at risk for participation.

• History of known intolerance/hypersensitivity to MPA, oral corticosteroids, or any component of the study drug(s) or its excipients

• Receipt of live/attenuated vaccine within a 4-week period prior to randomization

• History of primary or secondary immunodeficiency, including a positive HIV test result

• History of malignancy of any organ system (other than localized basal cell carcinoma or squamous cell carcinoma of the skin or or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases

• Any surgical, medical (e.g., uncontrolled hypertension, heart failure or diabetes), psychiatric or additional physical condition that the Investigator feels may jeopardize the participants in case of participation in this study

• Chronic infection with hepatitis B (HBV) or hepatitis C (HCV). Positive serology for hepatitis B surface antigen (HBsAg) excludes the participant

• Evidence of active tuberculosis (TB) infection (after anti-TB treatment, participants with history of TB may become eligible according to national local guidelines)

• Pregnant or nursing (lactating) women

• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 6 months after stopping of investigational medication

• Sexually active male participants, who do not agree to use barrier protection during intercourse with women of child-bearing potential while taking study treatment

Other protocol -defined Inclusion/Exclusion may apply.

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

Intervention

Drug:
• ianalumab s.c. q4w
ianalumab s.c. q4w in addition to SoC
• ianalumab s.c. q12w
ianalumab s.c. q12w in addition to SoC
• placebo s.c.
placebo s.c. q4w in addition to SoC

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Buenos Aire
Argentina	Novartis Investigative Site	Tucuman
Brazil	Novartis Investigative Site	Belo Horizonte	MG
Brazil	Novartis Investigative Site	Curitiba	PR
Brazil	Novartis Investigative Site	Juiz de Fora	MG
Brazil	Novartis Investigative Site	Pernambuco	Recife
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Salvador	BA
Brazil	Novartis Investigative Site	Salvador
Brazil	Novartis Investigative Site	Santo Andre	SP
Brazil	Novartis Investigative Site	Sao Luis	Maranhao
Brazil	Novartis Investigative Site	Vitoria	ES
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Sherbrooke	Quebec
Chile	Novartis Investigative Site	Santiago	RM
Chile	Novartis Investigative Site	Temuco
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Binzhou	Shandong
China	Novartis Investigative Site	Changchun	Jilin
China	Novartis Investigative Site	Changsha	Hunan
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Chongqing
China	Novartis Investigative Site	Guang Zhou
China	Novartis Investigative Site	Guangzhou
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Haikou	Hainan
China	Novartis Investigative Site	Hefei	Anhui
China	Novartis Investigative Site	Linyi	Shandong
China	Novartis Investigative Site	Liuzhou	Guangxi
China	Novartis Investigative Site	Nanchang	Jiangxi
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shantou	Guangdong
China	Novartis Investigative Site	Shenyang	Liaoning
China	Novartis Investigative Site	Shenzhen	Guangdong
China	Novartis Investigative Site	Shenzhen	Guangdong
China	Novartis Investigative Site	Wuhan	Hubei
China	Novartis Investigative Site	Wuhan
China	Novartis Investigative Site	Xi'an	Shanxi
China	Novartis Investigative Site	Zhanjing	Guangong
China	Novartis Investigative Site	Zhejiang
Colombia	Novartis Investigative Site	Barranquilla
Colombia	Novartis Investigative Site	Bogota	Cundinamarca
Colombia	Novartis Investigative Site	Medellin	Antioquia
Czechia	Novartis Investigative Site	Olomouc
Czechia	Novartis Investigative Site	Prague 2
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tallinn
France	Novartis Investigative Site	Angers
France	Novartis Investigative Site	Besancon Cedex
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Grenoble
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Poitiers
Germany	Novartis Investigative Site	Aachen
Germany	Novartis Investigative Site	Herne
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Regensburg	Bavaria
Guatemala	Novartis Investigative Site	Guatemala
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Quetzaltenango
Hong Kong	Novartis Investigative Site	Kwun Tong	Kowloon
Hong Kong	Novartis Investigative Site	Tuen Mun
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Kaposvar
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Chandigarh
India	Novartis Investigative Site	Lucknow	Uttar Pradesh
India	Novartis Investigative Site	Secunderabad	Telangana
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Foggia	FG
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Pavia	PV
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Torino	TO
Italy	Novartis Investigative Site	Udine	UD
Korea, Republic of	Novartis Investigative Site	Bundang Gu	Gyeonggi Do
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Daegu
Korea, Republic of	Novartis Investigative Site	Daejeon	Korea
Korea, Republic of	Novartis Investigative Site	Gwangju
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Suwon si	Gyeonggi Do
Lithuania	Novartis Investigative Site	Kaunas	LTU
Lithuania	Novartis Investigative Site	Vilnius
Malaysia	Novartis Investigative Site	Kuala Lumpur
Malaysia	Novartis Investigative Site	Kuala Terengganu	Terengganu
Malaysia	Novartis Investigative Site	Sibu	Sarawak
Mexico	Novartis Investigative Site	Leon	Guanajuato
Mexico	Novartis Investigative Site	Monterrey	Nuevo Leon
Mexico	Novartis Investigative Site	Oaxaca
Mexico	Novartis Investigative Site	Queretaro
Mexico	Novartis Investigative Site	Queretaro
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Cluj Napoca
Romania	Novartis Investigative Site	Oradea	Jud Bihor
Romania	Novartis Investigative Site	Ramnicu Valcea	Valcea
Romania	Novartis Investigative Site	Timisoara
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	El Palmar	Murcia
Spain	Novartis Investigative Site	La Laguna	Santa Cruz De Tenerife
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Santiago De Compostela	Galicia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Vigo	Pontevedra
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Thailand	Novartis Investigative Site	Hat Yai	Songkla
United Kingdom	Novartis Investigative Site	Bradford	West Yorkshire
United Kingdom	Novartis Investigative Site	London
United States	VA NM Healthcare System	Albuquerque	New Mexico
United States	Fides Clinical Research	Atlanta	Georgia
United States	University Of Alabama UAB main campus	Birmingham	Alabama
United States	James J Peters VA Medical Center	Bronx	New York
United States	University Of Cincinnati .	Cincinnati	Ohio
United States	NY Nephrology	Clifton Park	New York
United States	Liberty Research Center	Dallas	Texas
United States	Univof Texas Southwestern Med Cntr Dept Of Pediatrics	Dallas	Texas
United States	Wayne State University	Detroit	Michigan
United States	Northern Assoc of Northern VA	Fairfax	Virginia
United States	University of Texas Medical Branch .	Galveston	Texas
United States	Mayo Clinic Jacksonville .	Jacksonville	Florida
United States	University of Kansas Medical Center CRAD001A2433	Kansas City	Kansas
United States	Parris and Associates Rheumatology	Lawrenceville	Georgia
United States	Wallace Rheumatic Study Center Research Department	Los Angeles	California
United States	Uni Wisconsin School Med Pub Health Clinical Research Office	Madison	Wisconsin
United States	UMC New Orleans Nephrologist	New Orleans	Louisiana
United States	University of California Irvine Research Department	Orange	California
United States	Circuit Clinical Clinical Research	Orchard Park	New York
United States	Univ of Pennsylvania Medical Center .	Philadelphia	Pennsylvania
United States	Uni of Texas Health Science Center	San Antonio	Texas
United States	Kaiser Permanente Dpt of Research and Evaluation	San Diego	California
United States	Baylor Scott and White Research	Temple	Texas
United States	Brookview Hills Research Assoc Brookwood Hills Research Assoc	Winston-Salem	North Carolina
Vietnam	Novartis Investigative Site	Hanoi
Vietnam	Novartis Investigative Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Brazil,  Canada,  Chile,  China,  Colombia,  Czechia,  Estonia,  France,  Germany,  Guatemala,  Hong Kong,  Hungary,  India,  Italy,  Korea, Republic of,  Lithuania,  Malaysia,  Mexico,  Romania,  Singapore,  Spain,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency and percentage of participants achieving stable Complete Renal Response (CRR)	The primary objective is to demonstrate superiority of ianalumab compared to placebo, in achieving stable CRR (defined as estimated glomerular filtration rate (eGFR) =90 ml/min/1.73 m2 or no less than 85% of baseline, AND, 24-hour UPCR <0.5 g/g) at Week 72 in active lupus nephritis (ISN/RPS class III, IV active glomerulonephritis with or without co-existing class V features, or pure class V membranous) participants on background SoC therapy.	Week 72
Secondary	Time to first occurrence of stable urine protein-to-creatinine ratio (UPCR) <0.5 g/g or =50% reduction from baseline	To demonstrate superiority of ianalumab, compared to placebo, in time to first occurrence of stable urine protein-to-creatinine ratio (UPCR) <0.5 g/g or =50% reduction from baseline up to Week 72	Week 72
Secondary	Percentage of participants achieving stable Overall Renal Response (ORR), defined as achievement as either Complete Renal Response (CRR) or Partial Renal Response (PRR)	To demonstrate superiority of ianalumab, compared to placebo, in achieving stable Overall Renal Response (ORR) at Week 48	Week 48
Secondary	Incidence of stable Complete Renal Response (CRR) while maintaining daily corticosteroid dose =5 mg/day	To demonstrate superiority of ianalumab, compared to placebo, in achieving stable Complete Renal Response (CRR) at Week 72 while maintaining daily corticosteroid dose =5 mg/day between Week 24 and Week 72	Week 72
Secondary	Incidence of renal-related event or death	To demonstrate superiority of ianalumab, compared to placebo, in preventing renal-related event or death through Week 72	Week 72
Secondary	Change in British Isles Lupus Activity Group (BILAG) score	To demonstrate superiority of ianalumab, compared to placebo in BILAG-2004 at Week 72	Week 72
Secondary	Change in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue score	To demonstrate superiority of ianalumab, compared to placebo, in FACIT-Fatigue at Week 72	Week 72
Secondary	Number of participants with treatment-emergent Adverse Events (AEs)	AEs are any untoward sign or symptom that occurs during the study treatment	Week 72
Secondary	Ianalumab concentration in serum	To characterize the pharmacokinetics (PK) of ianalumab mean, median, minimum and maximum concentrations will be provided	Week 72
Secondary	Incidence and titer of anti-ianalumab antibodies in serum (ADA assay) over time	To evaluate immunogenicity of ianalumab	Week 72