Ianalumab for Sjögren's Syndrome

(NEPTUNUS-1 Trial)

Recruiting at 103 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

276 Participants Needed

Trial Summary

What is the purpose of this trial?

A randomized, double-blind, placebo controlled, 2-arm multicenter phase 3 study to assess the efficacy and safety of ianalumab in patients with active Sjogren's syndrome (NEPTUNUS-1)

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.

What data supports the effectiveness of the drug Ianalumab (VAY736) for treating Sjögren's Syndrome?

Research shows that Ianalumab (VAY736) has two ways of reducing B cells, which are part of the immune system, and has shown preliminary effectiveness in treating Sjögren's Syndrome, an autoimmune disease causing dry eyes and mouth. ^{1 2 3 4 5}

Is ianalumab (VAY736) safe for humans?

Ianalumab (VAY736) has been tested in clinical trials for primary Sjögren's syndrome, and these studies have evaluated its safety. While specific safety details are not provided, the trials were designed to assess both safety and effectiveness, indicating that safety data was collected. ^{1 2 3 4 6}

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, as there are currently no disease-modifying drugs specifically for Sjögren's syndrome. ^{1 2 3 4 7}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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 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 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]

References

1. 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]

2. 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]

3. England 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. [2021]

4. Italy pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

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

6. 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]

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

Rationale for treating primary Sjögren's syndrome patients with an anti-CD6 monoclonal antibody (Itolizumab). [2021]