Ianalumab for Sjögren's Syndrome

(NEPTUNUS-1 Trial)

Not currently recruiting at 120 trial locations

Overseen By Steven Carsons

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Hydroxychloroquine, Methotrexate, Azathioprine, Corticosteroids

Must not be taking: DMARDs, Immunosuppressants, Corticosteroids, others

Disqualifiers: Other autoimmune diseases, Active infections, Malignancy, 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: Unknown

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests ianalumab, a new treatment for people with active Sjögren's syndrome, to determine its effectiveness and safety. Participants will receive either ianalumab or a placebo (a substance with no therapeutic effect) for comparison. It is suitable for those who have had Sjögren's syndrome for less than 7.5 years, have a positive anti-Ro/SSA antibody, and a specific level of disease activity affecting areas like joints or glands. As a Phase 3 trial, this study is the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising new treatment.

Will I have to stop taking my current medications?

You may need to stop taking certain medications before joining the trial. If you are on hydroxychloroquine, methotrexate, or azathioprine, you can continue them if your dose has been stable for at least 30 days. However, if you are taking other specific medications like certain Traditional Chinese Medicines or disease-modifying drugs not allowed by the protocol, you will need to stop them at least 30 days before starting the trial.

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

Research has shown that ianalumab, the treatment under study for Sjögren's syndrome, has been safe in past studies. Patients who took ianalumab experienced lasting benefits and tolerated the treatment well for up to two years. One study specifically found that ianalumab was well tolerated for up to 52 weeks, with patients continuing to benefit. These earlier findings suggest that ianalumab may be safe for people. ^{1 2 3 4 5}

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

Ianalumab is unique because it targets the BAFF receptor, which plays a crucial role in the immune system's activity, especially in autoimmune conditions like Sjögren's Syndrome. Unlike current treatments that primarily manage symptoms or suppress the immune system broadly, Ianalumab offers a more targeted approach by directly interfering with the signaling pathways that drive the disease. Researchers are excited about this treatment because it promises to provide relief by precisely modulating the immune response, potentially reducing side effects and improving patients' quality of life.

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

Research has shown that ianalumab, which participants in this trial may receive, can help reduce symptoms in people with Sjögren's syndrome. In one study, patients who took ianalumab experienced a noticeable improvement in their symptoms compared to those who took a placebo, a harmless pill with no active medicine. Specifically, their scores on a scale measuring disease activity dropped more than those of the placebo group. This improvement appeared by Week 16 and continued through Week 48. Additionally, ianalumab proved safe over two years of follow-up. These findings suggest that ianalumab may effectively relieve symptoms for those with Sjögren's syndrome. ^{2 3 6 7 8}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Adults with active Sjogren's Syndrome, diagnosed within the last 7.5 years and meeting specific criteria including certain symptom scores and antibody presence or positive biopsy. Stable doses of some medications like hydroxychloroquine, methotrexate, or low-dose corticosteroids are allowed. Exclusions include recent B-cell therapy use, significant lab abnormalities, dryness-causing medication changes, immunodeficiencies, chronic infections like hepatitis or TB, pregnancy/breastfeeding without contraception use.

Inclusion Criteria

Signed informed consent must be obtained prior to participation in the study

Patients negative for anti-Ro/SSA antibody are eligible, if they have a positive salivary gland biopsy confirmed by central expert review

Classification of Sjögren's syndrome according to the ACR/EULAR 2016 criteria

Exclusion Criteria

I have had a major organ, stem cell, or bone marrow transplant.

I do not have active hepatitis C or have cleared the virus after treatment.

I have not had any cancer, except for skin basal cell carcinoma, cervical cancer in situ, or Sjögren's related lymphoma, in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ianalumab or placebo subcutaneously monthly

48 weeks

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Ianalumab (VAY736)
• Placebo

Trial Overview The trial is testing Ianalumab (VAY736), a potential new treatment for Sjogren's Syndrome against a placebo in a randomized double-blind setup to evaluate its effectiveness and safety. Participants will be randomly assigned to either receive Ianalumab or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 1 Intervention

ianalumab

Group II: Arm B Placebo Group 1 Intervention

placebo

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 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 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 52 patients with primary Sjögren's syndrome, rituximab treatment led to a statistically significant improvement in salivary gland ultrasound scores compared to placebo, indicating its efficacy in this condition.

Specifically, the rituximab group showed notable improvements in glandular definition, with odds ratios suggesting a strong likelihood of response at both 16 and 48 weeks, supporting the potential of B cell depletion therapies in managing primary Sjögren's syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of rituximab on a salivary gland ultrasound score in primary Sjögren's syndrome: results of the TRACTISS randomised double-blind multicentre substudy. Fisher, BA., Everett, CC., Rout, J., et al.[2021]

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]

Citations

1. 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 ...

2. empr.com empr.com/reports/ianalumab-improves-outcomes-in-patients-with-sjogren-disease/

Ianalumab Improves Outcomes in Patients With Sjögren ... Findings from NEPTUNUS-1 showed ianalumab once monthly statistically significantly improved ESSDAI score compared with placebo at week 48 (least ...

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 ... Compared to placebo, ianalumab achieved a numerically greater reduction in disease activity by Week 16 with improvements sustained through Week ...

4. 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.

5. fiercebiotech.com fiercebiotech.com/biotech/novartis-drug-reduces-sjogrens-activity-and-patient-burden-trials-see-high-placebo-effect

Novartis' phase 3 wins in Sjögren's see high placebo effect Patients receiving ianalumab experienced an average score drop of 6.4 from baseline, compared to a decline of 5.1 score decline for the placebo ...

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

NCT02962895 | Safety and Efficacy of VAY736 in Patients ... Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjogren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b ...

7. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(21)02251-0/abstract

a randomised, double-blind, placebo-controlled, phase 2b ... Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren's syndrome: a randomised, double-blind, placebo-controlled, phase 2b ...

8. 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.