NEPTUNUS-2: Three-arm Study to Assess Efficacy and Safety of Ianalumab (VAY736) in Patients With Active Sjögren's Syndrome
Study Details
Study Description
Brief Summary
A randomized, double-blind, placebo controlled, 3-arm multicenter phase 3 study to assess the efficacy and safety of ianalumab in patients with active Sjögren's syndrome (NEPTUNUS-2)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Three-arm study of the clinical efficacy, safety and tolerability of ianalumab (VAY736) in patients with active Sjögren's syndrome. The purpose of this study is to demonstrate the clinical efficacy, safety and tolerability of ianalumab (VAY736) administered subcutaneously (s.c.) monthly or every 3 months compared to placebo in patients with active Sjögren's syndrome.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm A ianalumab exposure level 1 |
Biological: VAY736
ianalumab s.c.
|
| Experimental: Arm B ianalumab exposure level 2 |
Biological: VAY736
ianalumab s.c.
|
| Placebo Comparator: Arm C placebo |
Other: Placebo
placebo s.c.
|
Outcome Measures
Primary Outcome Measures
- Change from baseline in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score at Week 48 as compared to placebo [48 weeks]
Efficacy (Plan A: US and US reference countries and Plan B: EU, other non-US Regions and EU reference countries)
Secondary Outcome Measures
- Proportion of patients achieving ≥3 points reduction from baseline in ESSDAI score at Week 48 [48 weeks]
Efficacy (Plan A and B)
- Proportion of patients achieving ESSDAI<5 at Week 48 [48 weeks]
Efficacy (Plan A and B)
- Proportion of patients achieving ≥3 points reduction from baseline in ESSDAI score at Week 24 [24 weeks]
Efficacy (Plan A and B)
- Change from baseline in stimulated whole salivary flow rate at Week 48 [48 weeks]
Efficacy (Plan A and B)
- Change from baseline in Physician's Global Assessment (PhGA) of disease activity at Week 48 [48 weeks]
Efficacy (Plan A and B)
- Change from baseline in Patient's Global Assessment (PaGA) of disease activity at Week 48 [48 weeks]
Efficacy (Plan A and B)
- Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score at Week 48 [48 weeks]
Efficacy (Plan A and B)
- Proportion of patients achieving meaningful improvement in the Sjogren's Syndrome Symptom Diary (SSSD) score at Week 48 [48 weeks]
Efficacy (Plan A)
- Proportion of patients achieving ≥ 1 point or 15% reduction from baseline in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) at Week 48 [48 weeks]
Efficacy (Plan B)
Other Outcome Measures
- Proportion of patients achieving ≥ 1 point or 15% reduction from baseline in ESSPRI at Week 48 [48 weeks]
Efficacy (Plan A)
- Proportion of patients achieving improvement in the SSSD score at Week 48 [48 weeks]
Efficacy (Plan B)
- Change from baseline in Schirmer's test over 48 weeks [48 weeks]
Efficacy (Plan A and B)
- Change from baseline in Clinical Disease Activity Index (CDAI) score over 48 weeks [48 weeks]
Efficacy (Plan A and B)
- Change from baseline in Clinical European League Against Rheumatism Sjogrens Syndrome Disease Activity Index (ClinESSDAI) at Week 48 [48 weeks]
Effficacy (Plan A and B)
- Incidence of Treatment-emergent AEs (TEAEs) /SAEs (Serious Adverse Event) from baseline to Week 52 [Baseline to Week 52]
Safety (Plan A and B)
- Incidence of Treatment Emergent Adverse Event (TEAEs)/Serious Adverse Events (SAEs) from Week 52 to end of study [Week 52 through study completion up to 2 years]
Safety (Plan A and B)
- Incidence of anti-ianalumab antibodies in serum Anti Drug Antibody (ADA) assay to end of study [through study completion up to 2 years]
Immunogenicity (Plan A and B)
- Ianalumab concentration in serum during the treatment and follow-up (up to the end of study) [through study completion up to 2 years]
Pharmacokinetics (Plan A and B)
Eligibility Criteria
Criteria
Inclusion criteria
-
Signed informed consent must be obtained prior to participation in the study
-
Women and men ≥ 18 years of age
-
Classification of Sjögren's syndrome according to the ACR/EULAR 2016 criteria
-
Time since diagnosis of Sjögren's of ≤ 7.5 years at screening
-
Positive anti-Ro/SSA antibody at screening
-
Patients negative for anti-Ro/SSA antibody are eligible, if they have a positive salivary gland biopsy confirmed by central expert review
-
Enrollment of anti-Ro/SSA-negative patients will be limited up to ≤10% of the study population
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Screening ESSDAI score of ≥ 5 within the following 8 domains: constitutional, lymphadenopathy, glandular, articular, cutaneous, renal, hematological and biologic.
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Stimulated whole salivary flow (sSF) rate of ≥ 0.05 mL/min at screening
-
Ability to communicate well with the Investigator, understand and agree to comply with the requirements of the study
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Patients taking hydroxychloroquine (≤ 400 mg/day), methotrexate (≤ 25 mg/week) or azathioprine (≤ 150 mg/day) alone or in combination, are allowed to continue their medication, and must have been on a stable dose for at least 30 days prior to randomization.
-
Patients taking systemic corticosteroids have to be on a stable dose of ≤ 10 mg/day predniso(lo)ne or equivalent for at least 30 days before randomization.
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Patients taking
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disease-modifying antirheumatic drugs (DMARDs) other than specifically allowed in inclusion criterion #9 or
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the following Traditional Chinese Medicines: Total glucoside of peony (TGP) or Tripterium glycosides (TG)
-
must discontinue these medications at least 30 days prior to randomization, except for leflunomide, which has to be discontinued for 8 weeks prior to randomization unless a cholestyramine wash-out has been performed.
Exclusion Criteria:
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Presence of another autoimmune rheumatic disease that is active and constitutes the principal illness
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Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days or until the expected pharmacodynamic effect has returned to baseline, whichever is longer3. Prior treatment with ianalumab
-
Prior use of a B-cell depleting therapy other than ianalumab within 36 weeks prior to randomization or as long as B-cell count is <50 cells/μL
-
Prior treatment with any of the following within 6 months prior to randomization:
-
iscalimab, belimumab , abatacept, anti-tumor necrosis factor alpha biologic agents, immunoglobulins plasmapheresis; i.v. or oral cyclophosphamide and mycophenolate mofetil, i.v. or oral cyclosporine A; any other immunosuppressants (e.g., JAK inhibitors or other kinase inhibitors) unless explicitly allowed by protocol
-
Use of corticosteroids (predniso(lo)ne or equivalent corticosteroid) at dose >10 mg/day
-
Any one of the following laboratory values at screening:
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Hemoglobin levels < 8.0 g/dL
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White blood cells (WBC) count < 2.0 x 10E3/µL
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Platelet count < 80 x 10E3/µL
-
Absolute neutrophil count (ANC) < 0.8 x 10E3/µL
-
Active viral, bacterial or other infections requiring systemic treatment at the time of screening or randomization, or history of recurrent clinically significant infection or of bacterial infections with encapsulated organisms
-
History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes (e.g., mAb of IgG1 class) or to any of the constituents of the study drug formulation (sucrose, L-histidine hydrochloride/ L-histidine, polysorbate 20)
-
History of major organ, hematopoietic stem cell or bone marrow transplant
-
Required regular use of medications known to cause dry mouth/eyes as a regular and major side effect, and which have not been on a stable dose for at least 30 days prior to Screening, or any anticipated change in the treatment regimen during the course of the study.
-
Use of topical ocular prescription medications (excluding artificial tears, gels, lubricants) that have not been on a stable dose for at least 90 days prior to randomization, or any anticipated change in the treatment regimen during the course of the study
-
Receipt of live/attenuated vaccine within a 4-week period prior to randomization
-
History of primary or secondary immunodeficiency, including a positive human immunodeficiency virus (HIV) test result
-
History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer or Sjögren's related lymphoma), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
-
History of sarcoidosis
-
Any surgical, medical (e.g., uncontrolled hypertension, heart failure or diabetes mellitus), psychiatric or additional physical condition that the Investigator feels may jeopardize the patient in case of participation in this study
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Chronic infection with hepatitis B (HBV) or hepatitis C (HCV). Positive serology for hepatitis B surface antigen (HBsAg) excludes the subject.
-
Evidence of active tuberculosis (TB) infection (after anti-TB treatment, patients with history of or latent TB may become eligible according to national guidelines)
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Pregnant or nursing (lactating) women,
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Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while on study treatment and for 6 months after stopping of investigational medication.
-
Patients with a known history of non-compliance to medication, or who were unable or unwilling to complete PRO questionnaires, or who are unable or unwilling to use the device for collection of PROs.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CVAY736A2302
- 2021-005687-22