Ianalumab for Sjogren's Syndrome
(NEPTUNUS-Ext Trial)
Recruiting in Palo Alto (17 mi)
+180 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Novartis Pharmaceuticals
Disqualifiers: Pregnancy, Live vaccines, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
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.
12345Is 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.
12678How 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.
1291011Eligibility 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.
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Ianalumab MonthlyExperimental Treatment1 Intervention
Ianalumab 300 mg s.c. monthly
Group II: Ianalumab 3 MonthlyExperimental Treatment2 Interventions
Ianalumab 300 mg s.c. every three months and placebo once monthly between doses
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Arthritis Osteoporosis Assoc of NMLas Cruces, NM
Altoona Center for Clin Res Main CenterDuncansville, PA
Novartis Investigative SiteRimouski, Canada
Bay Area Arthritis And OsteoporosisBrandon, FL
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Novartis PharmaceuticalsLead Sponsor
References
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]Sjögren's syndrome is an autoimmune disease characterised by dry eyes and mouth, systemic features, and reduced quality of life. There are no disease-modifying treatments. A new biologic, ianalumab (VAY736), with two modes of suppressing B cells, has previously shown preliminary efficacy. This dose-finding trial aimed to assess the safety and efficacy of different subcutaneous doses of ianalumab in patients with moderate to severe primary Sjögren's syndrome.
Treatment of primary Sjögren's syndrome with ianalumab (VAY736) targeting B cells by BAFF receptor blockade coupled with enhanced, antibody-dependent cellular cytotoxicity. [2020]To evaluate the efficacy and safety of ianalumab (VAY736), a B cell-depleting, B cell activating factor receptor-blocking, monoclonal antibody, in patients with active primary Sjögren's syndrome (pSS) in a double-blind, placebo-controlled, phase II, single-centre study.
Stratifying primary Sjögren's syndrome: killers in the balance? [2018]The article by Seror et al. in Arthritis Research & Therapy reports data from the 15 French patients in the open-label BELISS (Efficacy and Safety of Belimumab in Subjects With Primary Sjögren's Syndrome, NCT01160666) study of belimumab in primary Sjögren's syndrome. The study identifies that higher baseline levels of natural killer cells in the peripheral blood and salivary glands are associated with non-response to belimumab therapy. Although caution is required given the open-label nature of the trial, this study adds to data already suggesting a role for natural killer cells in primary Sjögren's syndrome and, importantly, indicates a need for therapeutic stratification.
Issues related to clinical trials of oral and biologic disease-modifying agents for Sjögren's syndrome. [2013]Published studies and trials of oral and biologic disease-modifying antirheumatic drugs for the treatment of Sjögren's syndrome have shown disappointing results. Improvements in trial design, including development of consortia for the conduct of national and international multicenter studies and use of standardized classification and outcome measures coupled with the emergence of newer biologic, immunomodulatory, and small molecule agents, hopefully will result in the addition of disease-modifying agents to the armamentarium.
A phase 2 randomized, double-blind, placebo-controlled, proof-of-concept study of oral seletalisib in primary Sjögren's syndrome. [2021]This phase 2 proof-of-concept study (NCT02610543) assessed efficacy, safety and effects on salivary gland inflammation of seletalisib, a potent and selective PI3Kδ inhibitor, in patients with moderate-to-severe primary Sjögren's syndrome (PSS).
Infliximab in primary Sjögren's syndrome: one-year followup. [2015]To evaluate the safety and efficacy of a maintenance regimen of infliximab in patients with active primary Sjögren's syndrome (SS) over a 1-year period.
Efficacy and safety of abatacept in active primary Sjögren's syndrome: results of a phase III, randomised, placebo-controlled trial. [2022]To evaluate efficacy and safety of abatacept in adults with active primary Sjögren's syndrome (pSS) in a phase III, randomised, double-blind, placebo-controlled trial.
Abatacept treatment reduces disease activity in early primary Sjögren's syndrome (open-label proof of concept ASAP study). [2022]To assess the efficacy and safety of abatacept in patients with early and active primary Sjögren's syndrome (pSS).
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]Sjögren's Syndrome (SjS) is a common chronic autoimmune disease characterized by the B cell hyperactivation, lymphocyte infiltration, and tissue damage of exocrine glands. It can also present life-threatening extraglandular manifestations, such as pulmonary and hepatic involvement, renal inflammation and marginal zone (MZ) B cell lymphoma. Several biologic agents have been tested in SjS but none has shown significant efficacy. Here, we report the effects of Ly9 (CD229) antibody targeting, a cell surface molecule that belongs to the SLAM family of immunomodulatory receptors, using NOD.H-2h4 mice as a model of SjS-like disease. Female mice were treated with anti-Ly9 antibody or isotype control at week 24, when all mice present SjS related autoantibodies, salivary gland infiltrates, and marginal zone (MZ) B cell pool enlargement. Antibody injection depleted key lymphocyte subsets involved in SjS pathology such as MZ, B1, and germinal center B cells in spleen and draining lymph nodes without inducing a general immunosuppression. Importantly, mice receiving anti-Ly9 mAb showed a reduced lymphocyte infiltrate within salivary glands. This reduction may be, in part, explained by the down-regulation of L-selectin and alfa4/beta7 integrin induced by the anti-Ly9 antibody. Furthermore, levels of anti-nuclear autoantibodies were reduced after anti-Ly9 treatment. These data indicate that Ly9 is a potential therapeutic target for the treatment of SjS.
Ianalumab (VAY736) in primary Sjögren's syndrome: assessing disease activity using multi-modal ultrasound. [2022]To apply serial ultrasound (US) assessments to show effects of ianalumab (anti-BAFF-R monoclonal antibody) on inflamed salivary glands of patients with primary Sjögren's syndrome (pSS).
Cytokines as therapeutic targets in primary Sjögren syndrome. [2019]Primary Sjögren syndrome (SjS) is a systemic autoimmune disease that may affect 1 in 1000 people (overwhelmingly women) and that can be a serious disease with excess mortality due to severe organ-specific involvements and the development of B cell lymphoma; systemic involvement clearly marks the disease prognosis, and strongly suggests the need for closer follow-up and more robust therapeutic management. Therapy is established according to the organ involved and severity. As a rule, the management of systemic SjS should be organ-specific, with glucocorticoids and immunosuppressive agents limited to potentially-severe involvements; unfortunately, the limited evidence available for these drugs, together with the potential development of serious adverse events, makes solid therapeutic recommendations difficult. The emergence of biological therapies has increased the therapeutic armamentarium available to treat primary SjS. Biologics currently used in SjS patients are used off-label and are overwhelmingly agents targeting B cells, but the most recent studies are moving on into the evaluation of targeting specific cytokines involved in the SjS pathogenesis. The most recent etiopathogenic advances in SjS are shedding some light in the search for new highly-selective biological therapies without the adverse effects of the standard drugs currently used (corticosteroids and immunosuppressant drugs). This review summarizes the potential pharmacotherapeutic options targeting the main cytokine families involved in the etiopathogenesis of primary SjS and analyzes potential insights for developing new therapies.