Clinical trial NCT05350072: Two-arm Study to Assess Efficacy and Safety of Ianalumab (VAY736) in Patients With Active Sjogren's Syndrome
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Sjogren Syndrome
Keywords: Sjogren's syndrome
B-cell depleting
BAFF-R
VAY736
ianalumab
NEPTUNUS
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-04-27
Enrollment: 276
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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)

Detailed description: Two-arm study of the clinical efficacy, safety and tolerability of ianalumab (VAY736) in patients with active Sjogren's syndrome. The purpose of the study is to demonstrate the clinical efficacy, safety and tolerability of ianalumab (VAY736) administered subcutaneously (s.c.) monthly compared to placebo in patients with active Sjogren's syndrome.

Eligibility 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
* Screening ESSDAI score of ≥ 5 within the following 8 domains: constitutional, lymphadenopathy, glandular, articular, cutaneous, renal, hematological and biologic.
* 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
* 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.
* Patients taking

  * disease-modifying antirheumatic drugs (DMARDs) other than specifically allowed by protocol
  * 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:

* Presence of another autoimmune rheumatic disease that is active and constitutes the principal illness
* 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 less than the lower limit of normal or baseline value prior to receipt of previous B cell-depleting therapy (whichever is lower)
* Prior treatment with any of the following:

  1. Within 24 weeks prior to randomization: iscalimab (anti CD-40 mAb), belimumab , abatacept, anti-tumor necrosis factor alpha biologic agents, immunoglobulins plasmapheresis;
  2. Within 12 weeks prior to randomization: i.v. or oral cyclophosphamide and mycophenolate mofetil, i.v. or oral cyclosporine A or 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:

  * Hemoglobin levels \< 8.0 g/dL
  * White blood cells (WBC) count \< 2.0 x 10E3/µL
  * 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 recurrent 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
* Chronic infection with hepatitis B (HBV) or hepatitis C (HCV) virus. Positive serology for hepatitis B surface antigen (HBsAg) excludes the subject.

  * HBsAg negative subjects who are hepatitis B core antibody (HBcAb) positive are also excluded unless all of the following criteria are met:

    1. HBV DNA is negative
    2. hepatitis B monitoring is implemented - in these subjects, monthly testing of HBsAg and HBV DNA must be performed while on study treatment and at least every 12 weeks after end of treatment for the entire duration of safety follow-up.
    3. Antiviral prophylaxis must be implemented before the first administration of the study treatment, and continued up to 12 months after the end of study treatment. If antiviral therapy cannot be given or if the patient is not willing to comply with the antiviral treatment requirement, the patient is not eligible for the study.
  * Hepatitis C: patients with positive hepatitis C antibody and HCV-RNA at screening are excluded. Chronic hepatitis C patients who have completed HCV anti-viral treatment must be HCV-RNA negative at least 12 weeks after treatment before randomization to be eligible. Cases of spontaneous HCV clearance should be discussed with sponsor before enrollment.
* Evidence of active tuberculosis (TB) infection is exclusionary. Patients with previously treated TB and previously treated or newly diagnosed latent TB may be eligible.
* Pregnant or nursing (lactating) women.
* 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.
* United States (and other countries, if locally required): Sexually active males, unless they agree to use barrier protection during intercourse with a woman of childbearing potential, while taking study treatment. As condom use alone has a reported failure rate exceeding 1% per year, it is recommended that female partners of male study participants use a second method of birth control. Although ianalumab is not teratogenic and/or genotoxic, and not transferred to semen, male contraception is required, as requested by FDA.

Globally, for all sexually active males, contraception should be used in accordance with locally approved prescribing information of concomitant medications administered.

Primary outcomes:
measure: Change from baseline in EULAR Sjogren Syndrome Disease Activity Index (ESSDAI) score at Week 48 as compared to placebo
timeFrame: 48 weeks
Secondary outcomes:
measure: Achieving ESSDAI response at Week 48
timeFrame: 48 weeks
measure: Achieving ESSDAI score <5 at Week 48
timeFrame: 48 weeks
measure: Achieving ESSDAI response at Week 24
timeFrame: 24 weeks
measure: Achieving SSSD response at Week 48
timeFrame: 48 weeks
measure: Change from baseline in stimulated whole salivary flow rate at Week 48
timeFrame: 48 weeks
measure: Change from baseline in Physician's Global Assessment (PhGA) of disease activity at Week 48
timeFrame: 48 weeks
measure: Change from baseline in Patient's Global Assessment (PaGA) of disease activity at Week 48
timeFrame: 48 weeks
measure: Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score at Week 48
timeFrame: 48 weeks
measure: Achieving EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) response at Week 48
timeFrame: 48 weeks
Other outcomes:
measure: Incidence of Treatment Emergent Adverse Event (TEAEs)/Serious Adverse Events (SAEs) upto the end of the study
timeFrame: through study completion upto 2 years
measure: Incidence of anti-ianalumab antibodies in serum Anti Drug Antibody (ADA) assay) up to end of study
timeFrame: through study completion up to 2 years
measure: Ianalumab concentration in serum during the treatment (example Ctrough) and follow-up (up to end of study)
timeFrame: through study completion up to 2 years
Locations:
city: Van Nuys
country: United States
facility: Medvin Clinical Research
state: California
city: Tamarac
country: United States
facility: West Broward Rheumatology Associates Inc
state: Florida
city: Indianapolis
country: United States
facility: Indiana Univ School of Dentistry
state: Indiana
city: Baton Rouge
country: United States
facility: Ochsner Health System
state: Louisiana
city: Baltimore
country: United States
facility: The John Hopkins Jerome L Greene Sjogren
state: Maryland
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: Wilmington
country: United States
facility: Carolina Arthritis Associates
state: North Carolina
city: Dayton
country: United States
facility: STAT Research Inc
state: Ohio
city: Duncansville
country: United States
facility: Altoona Center for Clin Res
state: Pennsylvania
city: Columbia
country: United States
facility: Prisma Health
state: South Carolina
city: Colleyville
country: United States
facility: Precision Comprehensive Research
state: Texas
city: Dallas
country: United States
facility: Metroplex Clinical Research
state: Texas
city: Houston
country: United States
facility: Baylor College Of Medicine
state: Texas
city: Katy
country: United States
facility: Houston Rheumatology & Arthrit
state: Texas
city: Graz
country: Austria
facility: Novartis Investigative Site
city: Stockerau
country: Austria
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Vitoria
country: Brazil
facility: Novartis Investigative Site
state: ES
city: Juiz de Fora
country: Brazil
facility: Novartis Investigative Site
state: MG
city: Ribeirao Preto
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Shenzhen
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Baotou
country: China
facility: Novartis Investigative Site
state: Inner Mongolia
city: Hohhot
country: China
facility: Novartis Investigative Site
state: Inner Mongolia
city: Nanchang
country: China
facility: Novartis Investigative Site
state: Jiangxi
city: Shenyang
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Linyi
country: China
facility: Novartis Investigative Site
state: Shandong
city: Taiyuan
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanxi
country: China
facility: Novartis Investigative Site
city: Brno
country: Czechia
facility: Novartis Investigative Site
city: Praha 11
country: Czechia
facility: Novartis Investigative Site
city: Uherske Hradiste
country: Czechia
facility: Novartis Investigative Site
city: Caen
country: France
facility: Novartis Investigative Site
city: Dijon
country: France
facility: Novartis Investigative Site
city: Lille
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Paris cedex 10
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: St Etienne
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Gommern
country: Germany
facility: Novartis Investigative Site
city: Ludwigshafen
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala
country: Guatemala
facility: Novartis Investigative Site
city: Quetzaltenango
country: Guatemala
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Gwangju
country: Korea, Republic of
facility: Novartis Investigative Site
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
city: Ciudad de Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
state: Dolnoslaskie
city: Bydgoszcz
country: Poland
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Lublin
country: Poland
facility: Novartis Investigative Site
city: Braga
country: Portugal
facility: Novartis Investigative Site
city: Guarda
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Sabadell
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Badalona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Bilbao
country: Spain
facility: Novartis Investigative Site
state: Pais Vasco
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Kocaeli
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: