Clinical trial NCT05349214: Three-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, 3-arm Multicenter Phase 3 Study to Assess the Efficacy and Safety of Ianalumab in Patients With Active Sjogren's Syndrome (NEPTUNUS-2)
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: 506
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, 3-arm multicenter phase 3 study to assess the efficacy and safety of ianalumab in patients with active Sjogren's syndrome (NEPTUNUS-2)

Detailed description: Three-arm study of the clinical efficacy, safety and tolerability of ianalumab (VAY736) in patients with active Sjogren'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 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 in inclusion criterion #9 or
  * 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, 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 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. Patient 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 Sjögren Syndrome Disease Activity Index (ESSDAI) score at Week 48 as compared to placebo
timeFrame: 48 weeks
Secondary outcomes:
measure: Proportion of patients achieving ≥3 points reduction from baseline in ESSDAI score at Week 48
timeFrame: 48 weeks
measure: Proportion of patients achieving ESSDAI<5 at Week 48
timeFrame: 48 weeks
measure: Proportion of patients achieving ≥3 points reduction from baseline in ESSDAI score at Week 24
timeFrame: 24 weeks
measure: Proportion of patients achieving meaningful improvement in the Sjogren's Syndrome Symptom Diary (SSSD) score 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: Proportion of patients achieving ≥ 1 point or 15% reduction from baseline in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) at Week 48
timeFrame: 48 weeks
Other outcomes:
measure: Incidence of Treatment-emergent AEs (TEAEs) /SAEs (Serious Adverse Event) upto the end of the study
timeFrame: Through study completion up to two years
measure: Incidence of anti-ianalumab antibodies in serum Anti Drug Antibody (ADA) assay to end of study
timeFrame: through study completion up to 2 years
measure: Ianalumab concentration in serum during the treatment and follow-up (up to the end of study)
timeFrame: throughout study completion up to 2 years
Locations:
city: Fullerton
country: United States
facility: Providence Medical Foundation
state: California
city: La Palma
country: United States
facility: Advanced Medical Research
state: California
city: Brandon
country: United States
facility: Bay Area Arthritis And Osteoporosis
state: Florida
city: Hollywood
country: United States
facility: GNP Research
state: Florida
city: Sarasota
country: United States
facility: Sarasota Arthritis Res Ctr
state: Florida
city: Augusta
country: United States
facility: Augusta University Georgia
state: Georgia
city: Lawrenceville
country: United States
facility: North Georgia Rheumatology Group
state: Georgia
city: Orland Park
country: United States
facility: Clin Invest Specialists Inc
state: Illinois
city: Skokie
country: United States
facility: Clinic of Robert Hozman
state: Illinois
city: Wauconda
country: United States
facility: Clinical Investigation Specialists, Inc.
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Boston
country: United States
facility: Tufts School of Dental Medicine
state: Massachusetts
city: Las Cruces
country: United States
facility: Arthritis Osteoporosis Assoc of NM
state: New Mexico
city: Potsdam
country: United States
facility: St Lawrence Health System
state: New York
city: Charlotte
country: United States
facility: On Site Clinical Solutions Llc
state: North Carolina
city: Charlotte
country: United States
facility: Arthritis and Osteoporosis
state: North Carolina
city: Oklahoma City
country: United States
facility: RAO Research LLS
state: Oklahoma
city: Jackson
country: United States
facility: West Tennessee Research Institute
state: Tennessee
city: Memphis
country: United States
facility: Ramesh C Gupta MD Memphis TN
state: Tennessee
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
city: San Antonio
country: United States
facility: First Outpatient Research Unit
state: Texas
city: Spring
country: United States
facility: Advanced Rheumatology of Houston
state: Texas
city: Spokane
country: United States
facility: Arthritis Northwest PLLC
state: Washington
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Tucuman
country: Argentina
facility: Novartis Investigative Site
state: San Miguel De Tucuman
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Maroochydore
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Woodville South
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Hobart
country: Australia
facility: Novartis Investigative Site
state: Tasmania
city: Salvador
country: Brazil
facility: Novartis Investigative Site
state: BA
city: Curitiba
country: Brazil
facility: Novartis Investigative Site
state: PR
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Burgas
country: Bulgaria
facility: Novartis Investigative Site
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Vancouver
country: Canada
facility: Novartis Investigative Site
state: British Columbia
city: Sydney
country: Canada
facility: Novartis Investigative Site
state: Nova Scotia
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Rimouski
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Trois Rivieres
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Valdivia
country: Chile
facility: Novartis Investigative Site
state: Los Rios
city: Santiago
country: Chile
facility: Novartis Investigative Site
state: RM
city: Concepcion
country: Chile
facility: Novartis Investigative Site
city: Hefei
country: China
facility: Novartis Investigative Site
state: Anhui
city: Chongqing
country: China
facility: Novartis Investigative Site
state: Chongqing
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nanchang
country: China
facility: Novartis Investigative Site
state: Jiangxi
city: Pingxiang
country: China
facility: Novartis Investigative Site
state: Jiangxi
city: Chang Chun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Taiyuan
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Yinchuan City
country: China
facility: Novartis Investigative Site
state: The Ningxia Hui Autonomous Reg
city: Urumqi
country: China
facility: Novartis Investigative Site
state: Xinjiang
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Xinxiang
country: China
facility: Novartis Investigative Site
city: Medellin
country: Colombia
facility: Novartis Investigative Site
state: Antioquia
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
state: Atlantico
city: Bucaramanga
country: Colombia
facility: Novartis Investigative Site
state: Santander
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Angers Cedex 9
country: France
facility: Novartis Investigative Site
city: Brest
country: France
facility: Novartis Investigative Site
city: Le Kremlin Bicetre
country: France
facility: Novartis Investigative Site
city: Le Mans
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Herne
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Szekesfehervar
country: Hungary
facility: Novartis Investigative Site
state: Fejer
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Eger
country: Hungary
facility: Novartis Investigative Site
city: Gyula
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Pune
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Kfar Saba
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Salerno
country: Italy
facility: Novartis Investigative Site
state: SA
city: Udine
country: Italy
facility: Novartis Investigative Site
state: UD
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Kitakyushu
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Sapporo city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Sapporo
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kuwana
country: Japan
facility: Novartis Investigative Site
state: Mie
city: Sasebo
country: Japan
facility: Novartis Investigative Site
state: Nagasaki
city: Kurashiki
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Meguro-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Culiacan
country: Mexico
facility: Novartis Investigative Site
state: Sinaloa
city: Merida
country: Mexico
facility: Novartis Investigative Site
state: Yucatan
city: Mexico
country: Mexico
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
state: Dolnoslaskie
city: Krakow
country: Poland
facility: Novartis Investigative Site
state: Malopolskie
city: Poznan
country: Poland
facility: Novartis Investigative Site
state: Wielkopolskie
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Brasov
country: Romania
facility: Novartis Investigative Site
city: Bucharest
country: Romania
facility: Novartis Investigative Site
city: Bucuresti
country: Romania
facility: Novartis Investigative Site
city: Cluj Napoca
country: Romania
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Kosice
country: Slovakia
facility: Novartis Investigative Site
city: Topolcany
country: Slovakia
facility: Novartis Investigative Site
city: Zvolen
country: Slovakia
facility: Novartis Investigative Site
city: Panorama
country: South Africa
facility: Novartis Investigative Site
state: Western Cape
city: Stellenbosch
country: South Africa
facility: Novartis Investigative Site
city: Cordoba
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Santander
country: Spain
facility: Novartis Investigative Site
state: Cantabria
city: Vigo
country: Spain
facility: Novartis Investigative Site
state: Pontevedra
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
state: SE
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Doncaster
country: United Kingdom
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
city: Swindon
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: