RECRUITING

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

Conditions

Lupus Nephritis SLE Systemic Lupus Erythematosus (SLE)Kidney inflammation Anti-BAFF-receptor B cell depletion Ianalumab VAY736

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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

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).

Quick Facts

Study Start:2022-07-14

Study Completion:2030-07-15

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05126277

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Study Contact

Novartis Pharmaceuticals

CONTACT

1-888-669-6682

novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Principal Investigator

Novartis Pharmaceuticals

STUDY_DIRECTOR

Novartis Pharmaceuticals

Study Locations (Sites)

University Of Alabama

Birmingham, Alabama, 35294

United States

Wallace Rheumatic Study Center

Los Angeles, California, 90048

United States

University of California LA

Los Angeles, California, 90095

United States

University of California Irvine

Orange, California, 92868

United States

UC Davis School of Medicine

Sacramento, California, 95817

United States

Kaiser Permanente

San Diego, California, 92111

United States

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224

United States

University Of Miami

Miami, Florida, 33136

United States

Emory University School of Medicine

Atlanta, Georgia, 30303

United States

Fides Clinical Research

Atlanta, Georgia, 30342

United States

Parris and Associates Rheumatology

Lawrenceville, Georgia, 30044

United States

University of Kansas Hospital

Kansas City, Kansas, 66160

United States

UMC New Orleans

New Orleans, Louisiana, 70112

United States

Wayne State University

Detroit, Michigan, 48201

United States

Univ of Nevada School of Med

Las Vegas, Nevada, 89102

United States

VA NM Healthcare System

Albuquerque, New Mexico, 87108

United States

James J Peters VA Medical Center

Bronx, New York, 10468

United States

NY Nephrology

Clifton Park, New York, 12065

United States

Hospital for Special Surgery

New York, New York, 10021

United States

Northwell Health

New York, New York, 10028

United States

Circuit Clinical

Orchard Park, New York, 14127

United States

Brookview Hills Research Assoc

Winston-Salem, North Carolina, 27103

United States

University Of Cincinnati

Cincinnati, Ohio, 45267

United States

Univ of Pennsylvania Medical Center

Philadelphia, Pennsylvania, 19104

United States

Liberty Research Center

Dallas, Texas, 75230

United States

Univof Texas Southwestern Med Cntr

Dallas, Texas, 75235

United States

University of Texas Medical Branch

Galveston, Texas, 77555-0144

United States

Uni of Texas Health Science Center

San Antonio, Texas, 78284

United States

Baylor Scott and White Research

Temple, Texas, 76502

United States

Northern Assoc of Northern VA

Fairfax, Virginia, 22033

United States

Uni Wisconsin School Med Pub Health

Madison, Wisconsin, 53792

United States

Collaborators and Investigators

Sponsor: Novartis Pharmaceuticals

Novartis Pharmaceuticals, STUDY_DIRECTOR, Novartis Pharmaceuticals

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-07-14

Study Completion Date2030-07-15

Study Record Updates

Study Start Date2022-07-14

Study Completion Date2030-07-15

Terms related to this study

Keywords Provided by Researchers

SLE
Systemic Lupus Erythematosus (SLE)
Kidney inflammation
Anti-BAFF-receptor
B cell depletion
Ianalumab
VAY736

Additional Relevant MeSH Terms

Lupus Nephritis