Clinical trial NCT05126277: Safety, Efficacy and Tolerability of Ianalumab Versus Placebo, Combination With SoC Therapy, in Participants With Active Lupus Nephritis
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).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Lupus Nephritis
Keywords: SLE
Systemic Lupus Erythematosus (SLE)
Kidney inflammation
Anti-BAFF-receptor
B cell depletion
Ianalumab
VAY736
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-11-19
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a pivotal double-blind, randomized, placebo-controlled, multi-center three-arm study, evaluating at Week 72 efficacy and safety of ianalumab administered s.c. every 4 weeks or ianalumab administered s.c. every 12 weeks versus placebo, administered s.c. every 4 weeks, in adult participants with active LN receiving SoC. In addition, long-term efficacy, safety and tolerability will be collected up to Week 144.
Primary purpose: TREATMENT

Brief 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

Detailed 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).

Eligibility criteria: 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-α 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.

Primary outcomes:
measure: Frequency and percentage of participants achieving stable Complete Renal Response (CRR)
timeFrame: Week 72
Secondary outcomes:
measure: Time to first occurrence of stable urine protein-to-creatinine ratio (UPCR) <0.5 g/g or ≥50% reduction from baseline
timeFrame: Week 72
measure: Percentage of participants achieving stable Overall Renal Response (ORR), defined as achievement as either Complete Renal Response (CRR) or Partial Renal Response (PRR)
timeFrame: Week 48
measure: Incidence of stable Complete Renal Response (CRR) while maintaining daily corticosteroid dose ≤5 mg/day
timeFrame: Week 72
measure: Incidence of renal-related event or death
timeFrame: Week 72
measure: Change in British Isles Lupus Activity Group (BILAG) score
timeFrame: Week 72
measure: Change in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue score
timeFrame: Week 72
measure: Number of participants with treatment-emergent Adverse Events (AEs)
timeFrame: Week 72
measure: Ianalumab concentration in serum
timeFrame: Week 72
measure: Incidence and titer of anti-ianalumab antibodies in serum (ADA assay) over time
timeFrame: Week 72
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University Of Alabama
state: Alabama
city: Los Angeles
country: United States
facility: Wallace Rheumatic Study Center
state: California
city: Los Angeles
country: United States
facility: University of California LA
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Sacramento
country: United States
facility: UC Davis School of Medicine
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: San Diego
country: United States
facility: Kaiser Permanente
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Miami
country: United States
facility: University Of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Atlanta
country: United States
facility: Fides Clinical Research
state: Georgia
city: Lawrenceville
country: United States
facility: Parris and Associates Rheumatology
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: New Orleans
country: United States
facility: UMC New Orleans
state: Louisiana
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Las Vegas
country: United States
facility: Univ of Nevada School of Med
state: Nevada
city: West Long Branch
country: United States
facility: Sahni Rheumatology and Therapy
state: New Jersey
city: Albuquerque
country: United States
facility: VA NM Healthcare System
state: New Mexico
city: Bronx
country: United States
facility: James J Peters VA Medical Center
state: New York
city: Clifton Park
country: United States
facility: NY Nephrology
state: New York
city: New York
country: United States
facility: Hospital for Special Surgery
state: New York
city: New York
country: United States
facility: Northwell Health
state: New York
city: Orchard Park
country: United States
facility: Circuit Clinical
state: New York
city: Winston-Salem
country: United States
facility: Brookview Hills Research Assoc
state: North Carolina
city: Cincinnati
country: United States
facility: University Of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: Univ of Pennsylvania Medical Center
state: Pennsylvania
city: Allen
country: United States
facility: Arthritis and Rheumatology Ins
state: Texas
city: Colleyville
country: United States
facility: Precision Comprehensive Research
state: Texas
city: Dallas
country: United States
facility: Liberty Research Center
state: Texas
city: Dallas
country: United States
facility: Univof Texas Southwestern Med Cntr
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: San Antonio
country: United States
facility: Uni of Texas Health Science Center
state: Texas
city: Temple
country: United States
facility: Baylor Scott and White Research
state: Texas
city: Fairfax
country: United States
facility: Northern Assoc of Northern VA
state: Virginia
city: Madison
country: United States
facility: Uni Wisconsin School Med Pub Health
state: Wisconsin
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: La Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Novartis Investigative Site
city: Tucuman
country: Argentina
facility: Novartis Investigative Site
city: Salvador
country: Brazil
facility: Novartis Investigative Site
state: BA
city: Vitoria
country: Brazil
facility: Novartis Investigative Site
state: ES
city: Sao Luis
country: Brazil
facility: Novartis Investigative Site
state: Maranhao
city: Belo Horizonte
country: Brazil
facility: Novartis Investigative Site
state: MG
city: Juiz de Fora
country: Brazil
facility: Novartis Investigative Site
state: MG
city: Curitiba
country: Brazil
facility: Novartis Investigative Site
state: PR
city: Pernambuco
country: Brazil
facility: Novartis Investigative Site
state: Recife
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Santo Andre
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Salvador
country: Brazil
facility: Novartis Investigative Site
city: Calgary
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Novartis Investigative Site
state: Manitoba
city: Etobicoke
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: London
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Santiago
country: Chile
facility: Novartis Investigative Site
state: RM
city: Temuco
country: Chile
facility: Novartis Investigative Site
city: Hefei
country: China
facility: Novartis Investigative Site
state: Anhui
city: Guang Zhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Shantou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Shenzhen
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Shenzhen
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Liuzhou
country: China
facility: Novartis Investigative Site
state: Guangxi
city: Haikou
country: China
facility: Novartis Investigative Site
state: Hainan
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Changsha
country: China
facility: Novartis Investigative Site
state: Hunan
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nanchang
country: China
facility: Novartis Investigative Site
state: Jiangxi
city: Changchun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Shenyang
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Binzhou
country: China
facility: Novartis Investigative Site
state: Shandong
city: Linyi
country: China
facility: Novartis Investigative Site
state: Shandong
city: Xian
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Beijing
country: China
facility: Novartis Investigative Site
city: Chongqing
country: China
facility: Novartis Investigative Site
city: Guang Zhou
country: China
facility: Novartis Investigative Site
city: Guangzhou
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Wuhan
country: China
facility: Novartis Investigative Site
city: Zhejiang
country: China
facility: Novartis Investigative Site
city: Medellin
country: Colombia
facility: Novartis Investigative Site
state: Antioquia
city: Bogota
country: Colombia
facility: Novartis Investigative Site
state: Cundinamarca
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
city: Olomouc
country: Czechia
facility: Novartis Investigative Site
city: Praha 2
country: Czechia
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Angers Cedex 9
country: France
facility: Novartis Investigative Site
city: Besancon Cedex
country: France
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Grenoble
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Poitiers
country: France
facility: Novartis Investigative Site
city: Regensburg
country: Germany
facility: Novartis Investigative Site
state: Bavaria
city: Aachen
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala
country: Guatemala
facility: Novartis Investigative Site
city: Quetzaltenango
country: Guatemala
facility: Novartis Investigative Site
city: Kwun Tong
country: Hong Kong
facility: Novartis Investigative Site
state: Kowloon
city: Tuen Mun
country: Hong Kong
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Kaposvar
country: Hungary
facility: Novartis Investigative Site
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Secunderabad
country: India
facility: Novartis Investigative Site
state: Telangana
city: Lucknow
country: India
facility: Novartis Investigative Site
state: Uttar Pradesh
city: Chandigarh
country: India
facility: Novartis Investigative Site
city: Cagliari
country: Italy
facility: Novartis Investigative Site
state: CA
city: Foggia
country: Italy
facility: Novartis Investigative Site
state: FG
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Pavia
country: Italy
facility: Novartis Investigative Site
state: PV
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Udine
country: Italy
facility: Novartis Investigative Site
state: UD
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Bundang Gu
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Suwon si
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi Do
city: Daejeon
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Busan
country: Korea, Republic of
facility: Novartis Investigative Site
city: Daegu
country: Korea, Republic of
facility: Novartis Investigative Site
city: Gwangju
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Kaunas
country: Lithuania
facility: Novartis Investigative Site
state: LTU
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
city: Sibu
country: Malaysia
facility: Novartis Investigative Site
state: Sarawak
city: Kuala Terengganu
country: Malaysia
facility: Novartis Investigative Site
state: Terengganu
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
state: Wilayah Persekutuan
city: Leon
country: Mexico
facility: Novartis Investigative Site
state: Guanajuato
city: Monterrey
country: Mexico
facility: Novartis Investigative Site
state: Nuevo Leon
city: Oaxaca
country: Mexico
facility: Novartis Investigative Site
city: Queretaro
country: Mexico
facility: Novartis Investigative Site
city: Queretaro
country: Mexico
facility: Novartis Investigative Site
city: Oradea
country: Romania
facility: Novartis Investigative Site
state: Jud Bihor
city: Ramnicu Valcea
country: Romania
facility: Novartis Investigative Site
state: Valcea
city: Bucharest
country: Romania
facility: Novartis Investigative Site
city: Bucuresti
country: Romania
facility: Novartis Investigative Site
city: Cluj Napoca
country: Romania
facility: Novartis Investigative Site
city: Timisoara
country: Romania
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Santiago De Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: El Palmar
country: Spain
facility: Novartis Investigative Site
state: Murcia
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Vigo
country: Spain
facility: Novartis Investigative Site
state: Pontevedra
city: La Laguna
country: Spain
facility: Novartis Investigative Site
state: Santa Cruz De Tenerife
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Songkhla
country: Thailand
facility: Novartis Investigative Site
state: Hat Yai
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Chiang Mai
country: Thailand
facility: Novartis Investigative Site
city: Bradford
country: United Kingdom
facility: Novartis Investigative Site
state: West Yorkshire
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Hanoi
country: Vietnam
facility: Novartis Investigative Site
city: Ho Chi Minh
country: Vietnam
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: