Ianalumab for Sjogren's Syndrome

(NEPTUNUS-Ext Trial)

Recruiting at 188 trial locations

Overseen By Novartis Pharmaceuticals

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: 0

Duration: 3 years

600 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to measure the long-term safety and tolerability of ianalumab in participants with Sjogrens syndrome who have previously completed treatment from one of two NEPTUNUS 1 year core studies (CVAY736A2301 \[NCT05350072\] or CVAY736A2302 \[NCT05349214\]). * The study treatment is ianalumab 300 mg in a 2 mL pre-filled syringe (PFS) or in a 2 mL autoinjector (AI) for injection. All participants will receive ianalumab either monthly or every 3 months. * The treatment duration will be 3 years with an additional up to 2-year safety follow-up. The total duration of this extension study will be up to 5 years. * The visit frequency will be monthly during both the treatment period and mandatory follow-up, and then less frequently during the subsequent conditional follow-up. Treatment of interest: The randomized treatment (ianalumab) will be received monthly or every 3 months. Participants assigned to treatment every 3 months will receive placebo every month between the ianalumab doses to maintain blinding. Number of Participants: Approximately 600 participants from the NEPTUNUS core studies will be rolled over into the extension study. Treatment Groups:There will be no screening period in this trial. From Week 48 of the NEPTUNUS core study, participants will be given the opportunity to consent to this extension study. From Week 52 of the NEPTUNUS core studies (i.e., Day 1 in the extension study), eligible participants will be assigned to either one of the treatment regimens: * ianalumab 300 mg monthly or * ianalumab 300 mg once every 3 months Participants receiving placebo in either of the NEPTUNUS core studies will be randomized 1:1 to receive ianalumab 300 mg monthly or every 3 months starting from Week 60 and participants receiving ianalumab in either of the NEPTUNUS core studies will continue the same treatment in the extension study. Ianalumab will be given as a subcutaneous injection from a 2 mL pre-filled syringe or a 2 mL autoinjector. Participants will be given the opportunity to self-inject at home on some visits after receiving training.

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.

What data supports the effectiveness of the drug Ianalumab for Sjogren's Syndrome?

Research shows that Ianalumab, a drug that targets B cells (a type of immune cell), has shown preliminary effectiveness in treating Sjögren's syndrome, an autoimmune disease causing dry eyes and mouth. It works by blocking a receptor on B cells and enhancing the body's ability to destroy these cells, which may help reduce symptoms. ^{1 2 3 4 5}

Is ianalumab (VAY736) safe for humans?

Ianalumab (VAY736) has been tested for safety in people with primary Sjögren's syndrome, an autoimmune disease. The studies were designed to check both safety and effectiveness, and they found that ianalumab was generally safe for use in humans. ^{1 2 6 7 8}

How is the drug ianalumab different from other treatments for Sjögren's syndrome?

Ianalumab is unique because it targets B cells in two ways: by blocking the BAFF receptor, which is involved in B cell survival, and by enhancing the body's ability to destroy these cells. This dual action is different from other treatments, which often do not specifically target B cells in this manner. ^{1 2 9 10 11}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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 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]

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 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]

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]

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]

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]

References

1. England 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. [2022]

2. England 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. [2020]

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

Stratifying primary Sjögren's syndrome: killers in the balance? [2018]

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

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

5. England 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. [2021]

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

Infliximab in primary Sjögren's syndrome: one-year followup. [2015]

7. England 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Abatacept treatment reduces disease activity in early primary Sjögren's syndrome (open-label proof of concept ASAP study). [2022]

9. Switzerland 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. [2019]

10. Italy pubmed.ncbi.nlm.nih.gov

Ianalumab (VAY736) in primary Sjögren's syndrome: assessing disease activity using multi-modal ultrasound. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Cytokines as therapeutic targets in primary Sjögren syndrome. [2019]