Ianalumab for Sjogren's Syndrome

(NEPTUNUS-Ext Trial)

Not currently recruiting at 236 trial locations

Overseen By Tamar Brionez

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Disqualifiers: Pregnancy, Live vaccines, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: Unknown

Duration: 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called ianalumab (also known as VAY736, NOV-5, or NVP-VAY736) to determine its safety and long-term tolerability for people with Sjogren's syndrome, an autoimmune disease that often causes dry eyes and mouth. Participants will receive the treatment either monthly or every three months, with some also receiving a placebo (inactive substance) to maintain study blinding. The trial is open to those who completed an earlier study with the same treatment, suggesting potential benefits from continued use. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the validation of a promising treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It mentions that certain therapies are excluded based on the NEPTUNUS study protocols, so it's best to discuss your specific medications with the study team.

Is there any evidence suggesting that ianalumab is likely to be safe for humans?

Research shows that ianalumab has a good safety record in patients. Earlier studies found that taking 300 mg of ianalumab was safe and well-tolerated for up to two years. Participants did not experience more infections, a common concern with treatments affecting the immune system. Overall, the treatment has shown positive results, with few serious side effects reported. This suggests ianalumab holds promise for long-term use in people with Sjogren's syndrome. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Sjogren's syndrome?

Researchers are excited about Ianalumab for Sjogren's Syndrome because it targets the condition in a unique way. Unlike typical treatments such as artificial tears or anti-inflammatory medications, Ianalumab is an antibody that targets and depletes B cells, which play a crucial role in the autoimmune response associated with Sjogren's Syndrome. This targeted approach could provide a more direct and potentially more effective treatment option. Additionally, the option for both monthly and every-three-month dosing offers flexibility and convenience for patients, potentially improving adherence and overall quality of life.

What evidence suggests that ianalumab might be an effective treatment for Sjogren's syndrome?

Research has shown that ianalumab can help reduce symptoms in people with Sjögren's syndrome. In this trial, participants will receive either 300 mg of ianalumab subcutaneously every three months or monthly. Earlier studies demonstrated that taking 300 mg of ianalumab provided lasting benefits and was safe for up to two years. Patients experienced significant symptom improvement, and the treatment was well-tolerated. This makes ianalumab a promising option for managing symptoms of Sjögren's syndrome. ^{1 3 4 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for people with Sjogren's Syndrome who finished a year of treatment in one of the NEPTUNUS core studies without stopping early. They should be able to keep taking ianalumab, as judged by their doctor, and have agreed to join this extension study.

Inclusion Criteria

I completed one of the NEPTUNUS studies without stopping the treatment.

My doctor believes ianalumab therapy will benefit me.

You have provided your written consent to participate in the study.

Timeline for a Trial Participant

Treatment

Participants receive ianalumab 300 mg either monthly or every 3 months for up to 3 years

3 years

Monthly visits

Mandatory Follow-up

Participants are monitored for safety and effectiveness after treatment for at least 20 weeks

20 weeks

Monthly visits

Conditional Follow-up

Participants continue follow-up if B-cell recovery criteria have not been met, up to 2 years

Up to 2 years

Less frequent visits

What Are the Treatments Tested in This Trial?

Interventions

• Ianalumab

Trial Overview The trial tests the long-term safety and effectiveness of ianalumab given monthly or every three months for up to five years. Participants will either continue their current regimen from previous studies or be randomly assigned a new schedule while maintaining blinding with placebo injections.

How Is the Trial Designed?

Group I: Ianalumab Monthly Experimental Treatment 1 Intervention

Ianalumab 300 mg s.c. monthly

Group II: Ianalumab 3 Monthly Experimental Treatment 2 Interventions

Ianalumab 300 mg s.c. every three months and placebo once monthly between doses

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

Ianalumab, a new biologic treatment for primary Sjögren's syndrome, demonstrated a dose-related decrease in disease activity after 24 weeks, with the most significant improvement seen in the 300 mg dose group.

The treatment was generally well tolerated, with no increase in infections reported, indicating a favorable safety profile for patients with moderate to severe disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b dose-finding trial. Bowman, SJ., Fox, R., Dörner, T., et al.[2022]

In a 24-week study involving 27 patients with primary Sjögren's syndrome, treatment with ianalumab (an anti-BAFF-R monoclonal antibody) led to significant improvements in the quality of inflamed salivary glands, as assessed by serial ultrasound imaging.

The ultrasound assessments indicated reductions in tissue inflammation and gland stiffness, suggesting that ianalumab may effectively improve salivary gland function without the need for invasive procedures like biopsies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ianalumab (VAY736) in primary Sjögren's syndrome: assessing disease activity using multi-modal ultrasound. Diekhoff, T., Fischer, T., Schefer, Q., et al.[2022]

In a phase III trial involving 187 adults with active primary Sjögren's syndrome, abatacept did not show significant clinical efficacy compared to placebo after 169 days, as measured by the primary endpoint of disease activity (ESSDAI).

Despite the lack of clinical benefit, abatacept demonstrated biological activity by affecting certain disease-relevant biomarkers and immune cell populations, with no new safety concerns identified during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of abatacept in active primary Sjögren's syndrome: results of a phase III, randomised, placebo-controlled trial. Baer, AN., Gottenberg, JE., St Clair, EW., et al.[2022]

Ianalumab (VAY736) demonstrated significant efficacy in reducing disease activity in patients with active primary Sjögren's syndrome, as shown by improvements in multiple clinical outcomes compared to placebo, including the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI).

The treatment resulted in rapid and sustained B cell depletion after a single infusion, with mild to moderate infusion reactions being the main side effects, indicating a favorable safety profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of primary Sjögren's syndrome with ianalumab (VAY736) targeting B cells by BAFF receptor blockade coupled with enhanced, antibody-dependent cellular cytotoxicity. Dörner, T., Posch, MG., Li, Y., et al.[2020]

Current studies on oral and biologic disease-modifying antirheumatic drugs for Sjögren's syndrome have not shown significant positive outcomes, indicating a need for better treatment options.

Future improvements in trial design, including multicenter studies and standardized measures, along with new drug developments, may enhance the effectiveness of treatments for Sjögren's syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Issues related to clinical trials of oral and biologic disease-modifying agents for Sjögren's syndrome. Carsons, SE.[2013]

In a follow-up study of 10 patients with active primary Sjögren's syndrome, a 1-year maintenance regimen of infliximab led to significant reductions in both global and local disease symptoms.

The treatment was generally well tolerated, with mild infusion reactions being the main side effect, suggesting that infliximab could be a safe and effective option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infliximab in primary Sjögren's syndrome: one-year followup. Steinfeld, SD., Demols, P., Appelboom, T.[2015]

In a study involving 15 patients with early and active primary Sjögren's syndrome, treatment with abatacept led to significant improvements in disease activity and quality of life, as measured by the ESSDAI and ESSPRI scales.

Abatacept was found to be safe and well-tolerated, with no serious side effects reported, indicating its potential as an effective treatment option for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abatacept treatment reduces disease activity in early primary Sjögren's syndrome (open-label proof of concept ASAP study). Meiners, PM., Vissink, A., Kroese, FG., et al.[2022]

Targeting the Ly9 (CD229) antibody in a mouse model of Sjögren's Syndrome effectively depleted harmful lymphocyte subsets involved in the disease, such as marginal zone and germinal center B cells, without causing general immunosuppression.

Treatment with anti-Ly9 antibody led to a significant reduction in lymphocyte infiltration in salivary glands and decreased levels of anti-nuclear autoantibodies, suggesting that Ly9 could be a promising therapeutic target for Sjögren's Syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ly9 (CD229) Antibody Targeting Depletes Marginal Zone and Germinal Center B Cells in Lymphoid Tissues and Reduces Salivary Gland Inflammation in a Mouse Model of Sjögren's Syndrome. Puñet-Ortiz, J., Sáez Moya, M., Cuenca, M., et al.[2019]

Primary Sjögren syndrome (SjS) is a serious autoimmune disease affecting primarily women, with a significant risk of severe organ involvement and B cell lymphoma, highlighting the need for careful monitoring and targeted treatment.

While traditional treatments like glucocorticoids and immunosuppressants have limited evidence and potential side effects, emerging biological therapies targeting specific cytokines involved in SjS pathogenesis offer promising new options for safer and more effective management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokines as therapeutic targets in primary Sjögren syndrome. Retamozo, S., Flores-Chavez, A., Consuegra-Fernández, M., et al.[2019]

In a study of 15 French patients with primary Sjögren's syndrome, higher baseline levels of natural killer cells were linked to a lack of response to belimumab treatment, suggesting these cells may play a significant role in the disease.

The findings highlight the importance of considering natural killer cell levels when determining treatment strategies for patients, indicating a need for personalized therapy approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stratifying primary Sjögren's syndrome: killers in the balance? Bowman, SJ., Fisher, BA.[2018]

In a phase 2 study involving 27 patients with moderate-to-severe primary Sjögren's syndrome, seletalisib showed a trend towards clinical improvement in disease activity scores, although the study was limited by early termination and reduced statistical power.

Seletalisib demonstrated positive effects on salivary gland inflammation, reducing the size and organization of inflammatory foci, and effectively engaged its target by inhibiting PI3K-mTOR signaling, despite no significant changes in saliva and tear flow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 randomized, double-blind, placebo-controlled, proof-of-concept study of oral seletalisib in primary Sjögren's syndrome. Juarez, M., Diaz, N., Johnston, GI., et al.[2021]

Citations

1. 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 ... These trials were designed to provide comprehensive data on the potential of ianalumab as a targeted treatment for Sjögren's disease, in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05350072

Two-arm Study to Assess Efficacy and Safety of Ianalumab ... Two-arm study of the clinical efficacy, safety and tolerability of ianalumab (VAY736) in patients with active Sjogren's syndrome.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39557617/

Safety and Efficacy of Ianalumab in Patients With Sjögren's ... In patients with SjD, ianalumab 300 mg demonstrated sustained efficacy through week 52 and a favorable safety profile up to two years of follow-up.

4. acrabstracts.org acrabstracts.org/abstract/ianalumab-demonstrates-significant-reduction-in-disease-activity-in-patients-with-sjogrens-disease-efficacy-and-safety-results-from-two-global-phase-3-randomized-placebo-controlled-double-blind-s/

Ianalumab demonstrates significant reduction in disease ... Ianalumab demonstrates significant reduction in disease activity in patients with Sjögren's disease: Efficacy and safety results from two ...

5. ard.bmj.com ard.bmj.com/content/80/Suppl_1/593

POS0692 IANALUMAB (VAY736) SAFETY AND ... Ianalumab 300 mg was well tolerated up to 52 Wks. Exploratory efficacy showed that continuous dosing of 300 mg sc q4w provided sustained clinical benefit.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02962895

NCT02962895 | Safety and Efficacy of VAY736 in Patients ... Higher scores on the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) scale are associated with poorer health states. A negative change from baseline ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34861168/

Safety and efficacy of subcutaneous ianalumab (VAY736) ... Overall, ianalumab was well tolerated and safe, with no increase in infections. To our knowledge, this is the first large, randomised, ...