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

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).

ClinicalTrials.gov Identifier: NCT05126277

Novartis Reference Number: CVAY736K12301

Last Update: Jul 26, 2022

See if you pre-qualify

All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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

Condition 
Lupus Nephritis
Phase 
Phase 3
Overall status 
Recruiting
Start date 
Jul 14, 2022
Completion date 
Jul 15, 2030
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

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

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 baseline

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 laboratory result

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

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 on 24h urine collection at Screening
eGFR ≥25mL/min/1.73 m2

Participants must be currently on, or willing to initiate SoC induction therapy for LN according to the institutional practices using MPA

Receipt of at least one dose of pulse methylprednisolone i.v. (500-1000 mg) or equivalent for treatment of current episode of active LN during past 60 days prior screening

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.) Stage 4 Chronic Kidney Disease (CKD), or ii.) presence of oliguria (defined as a documented urine volume <400 mL/24 hrs), or iii.) 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

Prior use of any B cell depleting therapy within 36 weeks prior to randomization or as long as B cell count <50 cells/μL

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

belimumab, 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 one of the following DMARDs: methotrexate or an imidazole derivative (e.g., azathioprine, mizoribine)

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

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
Platelet count <75 x 1000/µL
Absolute neutrophil count (ANC) <1.0 x 1000/µL

Active viral, bacterial or other infections requiring systemic treatment at the time of screening, or history of recurrent clinically significant infection or of bacterial infections with encapsulated organisms

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 patient 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 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

Study Locations

United States
Novartis Investigative Site
Recruiting
Fairfax, 22033
Virginia
United States
China
Novartis Investigative Site
Recruiting
Guang Zhou, 510080
-
China
Czech Republic
Novartis Investigative Site
Recruiting
Prague 2, 128 50
-
Czech Republic
Germany
Novartis Investigative Site
Recruiting
Regensburg, 93053
Bavaria
Germany
Novartis Investigative Site
Recruiting
Aachen, 52074
-
Germany
Novartis Investigative Site
Recruiting
Herne, 44625
-
Germany
Hungary
Novartis Investigative Site
Recruiting
Budapest, 1097
-
Hungary
Novartis Investigative Site
Recruiting
Debrecen, 4032
-
Hungary
Novartis Investigative Site
Recruiting
Kaposvar, 7400
-
Hungary
Korea, Republic of
Novartis Investigative Site
Recruiting
Gwangju, 61469
-
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 04763
-
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 05030
-
Korea, Republic of
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08003
Catalunya
Spain
Novartis Investigative Site
Recruiting
El Palmar, 30120
Murcia
Spain
Novartis Investigative Site
Recruiting
La Laguna, 38320
Santa Cruz De Tenerife
Spain
Novartis Investigative Site
Recruiting
Madrid, 28041
-
Spain

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals
Phone: 

Have a question?

Call 1-888-669-6682 or email [email protected]