Ianalumab + Standard Therapy for Lupus Nephritis

(SIRIUS-LN Trial)

Recruiting at195 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Novartis Pharmaceuticals

Must be taking: Corticosteroids, MPA

Must not be taking: Immunosuppressants, DMARDs

Disqualifiers: Severe renal impairment, Transplant history, Active infections, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial will test how well ianalumab injections work and how safe they are for adults with a type of kidney inflammation caused by lupus. The medication is given under the skin at regular intervals. It aims to reduce kidney inflammation by calming the immune system.

Will I have to stop taking my current medications?

The trial requires participants to switch from azathioprine to MPA before starting the study. Other medications like certain immunosuppressants and investigational drugs must be stopped before joining the trial. The protocol does not specify a washout period for all medications, so it's best to discuss your specific medications with the study team.

What makes the drug ianalumab unique for treating lupus nephritis?

Ianalumab is unique because it targets a specific protein involved in the immune response, potentially offering a new approach compared to existing treatments like voclosporin or anifrolumab, which have different mechanisms of action. ^{1 2 3 4 5}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

Adults with active Lupus Nephritis (LN) who have started or are willing to start standard treatment, including high-dose corticosteroids and MPA. They must weigh at least 35 kg, have a positive ANA test, and meet specific criteria for active LN. Excluded are those with severe kidney damage, recent heavy steroid use, certain infections or immunodeficiencies, cancer history within 5 years, or women who could become pregnant not using effective contraception.

Inclusion Criteria

I am 18 years old or older.

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

You have a positive anti-nuclear antibody (ANA) test result with a certain level of ANA in your blood.

Exclusion Criteria

I agree to use barrier protection during sex while on the study treatment.

I have had cancer in any part of my body in the last 5 years.

I have an active TB infection.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous ianalumab every 4 weeks or every 12 weeks, or placebo, in combination with standard of care therapy

72 weeks

18 visits (in-person) for q4w group, 6 visits (in-person) for q12w group

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• ianalumab (Monoclonal Antibodies)

Trial Overview The trial is testing the effectiveness of Ianalumab administered under the skin every 4 weeks or every 12 weeks versus a placebo. All treatments will be given in combination with standard-of-care therapy for LN. The goal is to see how well Ianalumab works and how safe it is compared to just receiving the usual treatment without this additional drug.

Participant Groups

Group I: Arm 2 - ianalumab s.c. q12w Experimental Treatment 1 Intervention

ianalumab s.c. q12w in addition to SoC

Group II: Arm 1 - ianalumab s.c. q4w Experimental Treatment 1 Intervention

ianalumab s.c. q4w in addition to standard of care (SoC)

Group III: Arm 3 - placebo s.c. q4w Placebo Group 1 Intervention

Placebo s.c. q4w in addition to SoC

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

Dapirolizumab pegol (DZP) showed improvements in clinical and immunological outcomes for patients with moderately to severely active systemic lupus erythematosus (SLE) after 24 weeks, although the primary dose-response relationship was not statistically significant.

DZP was well tolerated with low incidences of serious adverse events, suggesting it is a safe option for SLE treatment, warranting further investigation into its clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2, randomized, placebo-controlled trial of dapirolizumab pegol in patients with moderate-to-severe active systemic lupus erythematosus. Furie, RA., Bruce, IN., Dörner, T., et al.[2022]

Voclosporin, when combined with mycophenolate mofetil and glucocorticoids, significantly improved complete renal response in lupus nephritis patients, with 43.7% achieving this outcome compared to 23.3% in the control group, based on an integrated analysis of 534 patients from two clinical trials.

The safety profile of voclosporin was comparable to the control, with similar rates of adverse events, most of which were mild to moderate, indicating that voclosporin is a safe and effective treatment option for lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on the Efficacy and Safety Profile of Voclosporin: An Integrated Analysis of Clinical Trials in Lupus Nephritis. Arriens, C., Teng, YKO., Ginzler, EM., et al.[2023]

In a phase II study involving 147 patients with active lupus nephritis, the primary endpoint of improved urine protein-creatinine ratio was not met for anifrolumab compared to placebo, indicating limited efficacy in this measure.

However, the intensified regimen of anifrolumab showed numerical improvements in secondary outcomes, such as complete renal response and sustained glucocorticoid reductions, although there was a higher incidence of herpes zoster in the anifrolumab groups compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis. Jayne, D., Rovin, B., Mysler, EF., et al.[2022]

Multitarget therapy using mycophenolate mofetil (MMF), tacrolimus (TAC), and steroids is significantly more effective than intravenous cyclophosphamide (IVC) for inducing complete renal remission in lupus nephritis, based on a meta-analysis of 8 trials involving 801 patients.

While multitarget therapy showed a better safety profile with fewer gastrointestinal symptoms and liver issues, it was associated with a higher incidence of new-onset hypertension compared to IVC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multitarget therapy versus intravenous cyclophosphamide in the induction treatment of lupus nephritis: a metaanalysis of randomized controlled trials Deng, J., Luo, L., Zhu, L., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase 2, randomized, placebo-controlled trial of dapirolizumab pegol in patients with moderate-to-severe active systemic lupus erythematosus. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Update on the Efficacy and Safety Profile of Voclosporin: An Integrated Analysis of Clinical Trials in Lupus Nephritis. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Anifrolumab in lupus nephritis: results from second-year extension of a randomised phase II trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis. [2022]

5. Turkey pubmed.ncbi.nlm.nih.gov

Multitarget therapy versus intravenous cyclophosphamide in the induction treatment of lupus nephritis: a metaanalysis of randomized controlled trials [2019]