Ianalumab + Standard Therapy for Lupus Nephritis

(SIRIUS-LN Trial)

Recruiting at 219 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

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) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 18

Duration: 72 weeks

462 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of ianalumab for individuals with lupus nephritis, a kidney issue associated with lupus. The trial compares ianalumab administered every 4 weeks or every 12 weeks with a placebo (a substance with no active drug), alongside standard care. It targets individuals with active lupus nephritis who are already on or willing to start specific medications for their condition. The trial aims to determine if ianalumab is safe and effective for these patients. Those diagnosed with lupus nephritis and currently receiving treatment might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to help potentially bring a new treatment to market.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ianalumab (also known as VAY736) has been well-tolerated in past studies. In one study, patients with systemic lupus erythematosus, a condition related to lupus nephritis, took ianalumab for up to 68 weeks. The results indicated that most patients handled the treatment well without serious problems. Some side effects were reported, but these were mostly mild to moderate.

Since this trial is in a late stage, there is already some confidence in the safety of ianalumab. Late-stage trials usually occur only if earlier studies have shown that the treatment is generally safe for people. While side effects can still happen, they are not expected to be severe or surprising. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lupus nephritis?

Researchers are excited about ianalumab for lupus nephritis because it represents a new approach in targeting the immune system. Unlike traditional treatments like corticosteroids and immunosuppressants, ianalumab is a monoclonal antibody that specifically targets the BAFF receptor, a key player in autoimmune activity. This precision could lead to better disease control with potentially fewer side effects. Additionally, ianalumab offers flexibility in administration, with options for dosing every four or twelve weeks, potentially improving convenience and adherence for patients.

What evidence suggests that ianalumab might be an effective treatment for lupus nephritis?

Research has shown that ianalumab may help reduce disease activity in conditions like lupus nephritis. In this trial, participants will receive ianalumab in one of two dosing schedules or a placebo. Studies have found that ianalumab can improve health outcomes according to both doctors and patients, potentially lessening the overall impact of the disease. Earlier trials demonstrated that ianalumab was generally well-tolerated and provided benefits with long-term use, including better lab results and fewer symptoms for people with systemic lupus conditions. These findings offer hope that ianalumab could effectively manage lupus nephritis. ^{1 2 3 4 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

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

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.

I weigh at least 35 kg.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• ianalumab

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

In the TULIP-LN trial involving 147 patients with active lupus nephritis, the intensified regimen of anifrolumab (900 mg followed by 300 mg) showed a higher rate of complete renal response at Week 104 compared to the basic regimen and placebo (27.3% vs 18.6% and 17.8%).

The safety profile of anifrolumab remained consistent over two years, with 72% of patients reporting at least one adverse event, but serious adverse events were relatively low, suggesting that anifrolumab is a tolerable treatment option for lupus nephritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anifrolumab in lupus nephritis: results from second-year extension of a randomised phase II trial. Jayne, D., Rovin, B., Mysler, E., et al.[2023]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05126277

Study Details | NCT05126277 | Safety, Efficacy and ... The primary objective is to demonstrate superiority of ianalumab compared to placebo, in achieving stable CRR (defined as estimated glomerular filtration rate ( ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03656562

NCT03656562 | Study the Efficacy and Safety of VAY736 ... This study is designed to evaluate the safety, tolerability, pharmacokinetics and therapeutic efficacy of treatment with either VAY736 (ianalumab) or CFZ533 ...

3. novartis.com novartis.com/news/media-releases/novartis-ianalumab-first-drug-reduce-disease-activity-and-patient-burden-sjogrens-disease-phase-iii-trials

Novartis ianalumab first drug to reduce disease activity and ... Ianalumab 300 mg monthly numerically improved physician- and patient-reported outcomes1. Nominal significance was observed in NEPTUNUS-1 and the ...

4. acrabstracts.org acrabstracts.org/abstract/safety-and-efficacy-of-subcutaneous-ianalumab-vay736-for-up-to-68-weeks-in-patients-with-systemic-lupus-erythematosus-results-from-phase-2-study/

Safety and Efficacy of Subcutaneous Ianalumab (VAY736) ... Conclusion: Treatment with ianalumab was well-tolerated, and data suggests longer exposure up to 1 year provides further clinical and laboratory benefits in ...

5. novartis.com novartis.com/clinicaltrials/study/nct05639114

Phase 3 Study to Evaluate Two Regimens of Ianalumab on ... The trial will evaluate efficacy, safety and tolerability of two regimens of ianalumab compared to placebo, given as monthly or quarterly subcutaneous (sc) ...

6. clinicaltrial.be clinicaltrial.be/en/details/36672?only_active=0&only_eligible=0&only_recruiting=0&per_page=20

Safety, Efficacy and Tolerability of Ianalumab Versus Pla... This trial will evaluate the efficacy, safety, and tolerability of subcutaneous (s.c.) ianalumab given every 4 weeks (q4w) or ianalumab given ...