Three-arm Study to Assess Efficacy and Safety of Ianalumab (VAY736) in Patients With Active Sjogren's Syndrome

Sjogren Syndrome Clinical Trial

— NEPTUNUS-2  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05349214
• Other study ID #: CVAY736A2302
• Secondary ID: 2021-005687-22
• Status: Recruiting
• Phase: Phase 3
• Start date: August 4, 2022
• Est. completion date: March 9, 2028

Study information

• Verified date: June 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 489
• Est. completion date: March 9, 2028
• Est. primary completion date: March 9, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Sjogren Syndrome
• Sjogren's Syndrome
• Syndrome

Intervention

Biological:
• VAY736
ianalumab s.c.
• VAY736
ianalumab s.c.

Other:
• Placebo
placebo s.c.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires
Argentina	Novartis Investigative Site	Quilmes	Buenos Aires
Argentina	Novartis Investigative Site	San Nicolas	Buenos Aires
Argentina	Novartis Investigative Site	Tucuman	San Miguel De Tucuman
Australia	Novartis Investigative Site	Hobart	Tasmania
Australia	Novartis Investigative Site	Maroochydore	Queensland
Australia	Novartis Investigative Site	Woodville	South Australia
Brazil	Novartis Investigative Site	Belo Horizonte	MG
Brazil	Novartis Investigative Site	Curitiba	PR
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Salvador	BA
Brazil	Novartis Investigative Site	Sao Paulo	SP
Bulgaria	Novartis Investigative Site	Burgas
Bulgaria	Novartis Investigative Site	Pleven
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Sofia
Canada	Novartis Investigative Site	Rimouski	Quebec
Canada	Novartis Investigative Site	Sherbrooke	Quebec
Canada	Novartis Investigative Site	Sydney	Nova Scotia
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Trois Rivieres	Quebec
Canada	Novartis Investigative Site	Vancouver	British Columbia
Chile	Novartis Investigative Site	Concepcion
Chile	Novartis Investigative Site	Santiago	RM
Chile	Novartis Investigative Site	Valdivia	Los Rios
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Chang Chun	Jilin
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Chongqing	Chongqing
China	Novartis Investigative Site	Guang Zhou
China	Novartis Investigative Site	Hangzhou	Zhejiang
China	Novartis Investigative Site	Hefei	Anhui
China	Novartis Investigative Site	Nanchang	Jiangxi
China	Novartis Investigative Site	Nanjing	Jiangsu
China	Novartis Investigative Site	Pingxiang	Jiangxi
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Taiyuan	Shanxi
China	Novartis Investigative Site	Tianjin
China	Novartis Investigative Site	Urumqi	Xinjiang
China	Novartis Investigative Site	Xian	Shanxi
China	Novartis Investigative Site	Xinxiang
China	Novartis Investigative Site	Yinchuan City	The Ningxia Hui Autonomous Reg
China	Novartis Investigative Site	Zhuzhou	Hunan
Colombia	Novartis Investigative Site	Barranquilla	Atlantico
Colombia	Novartis Investigative Site	Bogota
Colombia	Novartis Investigative Site	Bucaramanga	Santander
Colombia	Novartis Investigative Site	Medellin	Antioquia
France	Novartis Investigative Site	Angers Cedex 9
France	Novartis Investigative Site	Bordeaux Cedex
France	Novartis Investigative Site	Brest
France	Novartis Investigative Site	Le Kremlin Bicetre
France	Novartis Investigative Site	Le Mans
France	Novartis Investigative Site	Strasbourg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Herne
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Luebeck
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Thessaloniki
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Eger
Hungary	Novartis Investigative Site	Gyula
Hungary	Novartis Investigative Site	Szeged
Hungary	Novartis Investigative Site	Szekesfehervar	Fejer
India	Novartis Investigative Site	Ahmedabad	Gujarat
India	Novartis Investigative Site	Ahmedabad	Gujarat
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Vellore	Tamil Nadu
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Kfar Saba
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Ancona	AN
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Salerno	SA
Italy	Novartis Investigative Site	Udine	UD
Japan	Novartis Investigative Site	Bunkyo ku	Tokyo
Japan	Novartis Investigative Site	Chiyoda-ku	Tokyo
Japan	Novartis Investigative Site	Chuo ku	Tokyo
Japan	Novartis Investigative Site	Hamamatsu-city	Shizuoka
Japan	Novartis Investigative Site	Itabashi-ku	Tokyo
Japan	Novartis Investigative Site	Kitakyushu-city	Fukuoka
Japan	Novartis Investigative Site	Kurashiki	Okayama
Japan	Novartis Investigative Site	Kuwana	Mie
Japan	Novartis Investigative Site	Meguro-ku	Tokyo
Japan	Novartis Investigative Site	Mito	Ibaraki
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Sapporo	Hokkaido
Japan	Novartis Investigative Site	Sapporo city	Hokkaido
Japan	Novartis Investigative Site	Sasebo-city	Nagasaki
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Yokohama	Kanagawa
Lebanon	Novartis Investigative Site	Ashrafieh
Lebanon	Novartis Investigative Site	Beirut
Mexico	Novartis Investigative Site	Culiacan	Sinaloa
Mexico	Novartis Investigative Site	Merida	Yucatan
Mexico	Novartis Investigative Site	Mexico
Poland	Novartis Investigative Site	Krakow	Malopolskie
Poland	Novartis Investigative Site	Poznan	Wielkopolskie
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Poland	Novartis Investigative Site	Wroclaw	Dolnoslaskie
Romania	Novartis Investigative Site	Brasov
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucuresti
Romania	Novartis Investigative Site	Cluj-Napoca
Romania	Novartis Investigative Site	Ramnicu Valcea	Valcea
Romania	Novartis Investigative Site	Targu Mures	Mures
Romania	Novartis Investigative Site	Timisoara	Timis
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigative Site	Nove Mesto nad Vahom
Slovakia	Novartis Investigative Site	Piestany
Slovakia	Novartis Investigative Site	Topolcany
Slovakia	Novartis Investigative Site	Zvolen
South Africa	Novartis Investigative Site	Panorama	Western Cape
South Africa	Novartis Investigative Site	Stellenbosch
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Cordoba	Andalucia
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Santander	Cantabria
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Vigo	Pontevedra
Sweden	Novartis Investigative Site	Stockholm	SE
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
United Kingdom	Novartis Investigative Site	Doncaster
United Kingdom	Novartis Investigative Site	Glasgow-Scotland
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	Liverpool
United Kingdom	Novartis Investigative Site	Newcastle Upon Tyme
United Kingdom	Novartis Investigative Site	Swindon
United States	Augusta University Georgia .	Augusta	Georgia
United States	Tufts School of Dental Medicine	Boston	Massachusetts
United States	Bay Area Arthritis And Osteoporosis	Brandon	Florida
United States	Arthritis and Osteoporosis	Charlotte	North Carolina
United States	OnSite Clinical Solutions Llc .	Charlotte	North Carolina
United States	Providence Medical Foundation	Fullerton	California
United States	GNP Research	Hollywood	Florida
United States	Novartis Investigative Site	Hopkinsville	Kentucky
United States	Prolato Clinical Research Center	Houston	Texas
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	University of Kansas Medical Center .	Kansas City	Kansas
United States	Advanced Medical Research Medical Research	La Palma	California
United States	Arthritis Osteoporosis Assoc of NM	Las Cruces	New Mexico
United States	North Georgia Rheumatology Group	Lawrenceville	Georgia
United States	Ramesh C Gupta MD Memphis TN	Memphis	Tennessee
United States	RAO Research LLS	Oklahoma City	Oklahoma
United States	Clin Invest Specialists Inc	Orland Park	Illinois
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Plantation	Florida
United States	St Lawrence Health System .	Potsdam	New York
United States	First Outpatient Research Unit	San Antonio	Texas
United States	Sarasota Arthritis Research Center	Sarasota	Florida
United States	Clinic of Robert Hozman	Skokie	Illinois
United States	Arthritis Northwest PLLC .	Spokane	Washington
United States	Advanced Rheumatology of Houston .	Spring	Texas
United States	Novartis Investigative Site	Van Nuys	California
United States	Novartis Investigative Site	Vestavia Hills	Alabama
United States	Clinical Investigation Special Inc .	Wauconda	Illinois
United States	Alliance for Multispecialty Resrch	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Colombia,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Japan,  Lebanon,  Mexico,  Poland,  Romania,  Slovakia,  South Africa,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of Treatment-emergent AEs (TEAEs) /SAEs (Serious Adverse Event) upto the end of the study	Safety (Plan A and B)	through study completion upto 2 years
Other	Incidence of anti-ianalumab antibodies in serum Anti Drug Antibody (ADA) assay to end of study	Immunogenicity (Plan A and B)	through study completion up to 2 years
Other	Ianalumab concentration in serum during the treatment and follow-up (up to the end of study)	Pharmacokinetics (Plan A and B)	through study completion up to 2 years
Primary	Change from baseline in EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) score at Week 48 as compared to placebo	Efficacy (Plan A: US and US reference countries and Plan B: EU, other non-US Regions and EU reference countries); Dose response measured by change multi-dimensional disease activity as assessed by the physician. Score range is 0-123. Higher scores on the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) scale are associated with poorer health states A negative change from baseline indicates improvement in disease status.	48 weeks
Secondary	Proportion of patients achieving =3 points reduction from baseline in ESSDAI score at Week 48	Efficacy (Plan A and B); Dose response measured by change multi-dimensional disease activity as assessed by the physician. Score range is 0-123. Higher scores on the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) scale are associated with poorer health states A negative change from baseline indicates improvement in disease status.	48 weeks
Secondary	Proportion of patients achieving ESSDAI<5 at Week 48	Efficacy (Plan A and B); Dose response measured by change multi-dimensional disease activity as assessed by the physician. Score range is 0-123. Higher scores on the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) scale are associated with poorer health states A negative change from baseline indicates improvement in disease status.	48 weeks
Secondary	Proportion of patients achieving =3 points reduction from baseline in ESSDAI score at Week 24	Efficacy (Plan A and B)	24 weeks
Secondary	Proportion of patients achieving meaningful improvement in the Sjogren's Syndrome Symptom Diary (SSSD) score at Week 48	Efficacy (Plan A); The Sjogrens Syndrome Symptom Diary (SSSD) is questionnaire consists of five (six for females) questions about symptoms of Sjögren's syndrome, each question given a score of 0-10 (0=no symptoms, 10=worst possible symptoms) where patient choose the one response that best describes how severe the symptom was at its worst in the PAST 24 HOURS. It includes six symptom items (eye dryness, mouth dryness, skin dryness, physical fatigue, muscle and/or joint pain, genital dryness), and applies a recall period of 24 hrs. The aim of the SSSD is to establish patient reported endpoints for the treatment of Sjogrens syndrome. Participants will complete the diary daily for 7 days prior to the scheduled dosing.	48 weeks
Secondary	Change from baseline in stimulated whole salivary flow rate at Week 48	Efficacy (Plan A and B); Both the amount and composition of saliva has been shown to reflect the glandular damage caused by the disease process of Sjögren's (Pijpe et al 2007). Unstimulated and stimulated salivary secretions are collected over 5 minutes. As much as possible the assessments are to be performed at a fixed time of the day to minimize fluctuations related to the circadian rhythm of salivary flow and composition (Dawes 1972).	48 weeks
Secondary	Change from baseline in Physician's Global Assessment (PhGA) of disease activity at Week 48	Efficacy (Plan A and B); Physician global assessment of disease activity is made with relation to Sjögren's syndrome. Physician's global assessment (PhGA) of disease activity for Sjögren's syndrome is performed using 3 separate scales: Visual Analog Scale (VAS) - an unnumbered 100 mm long horizontal line ranging from "no disease activity' to "maximal disease activity". The assessment of patient's condition on the day is made by placing a vertical mark across the line.; Numerical Rating Scale (NRS) - a segmented numeric version of the VAS. A respondent needs to select a whole number (0-10 integers), with 0 being "no disease activity" and 10 being "maximal disease activity".; 4-point Likert scale - The level of disease activity is assessed on a scale from "inactive" to "high activity".	48 weeks
Secondary	Change from baseline in Patient's Global Assessment (PaGA) of disease activity at Week 48	Efficacy (Plan A and B); Patient's global assessment (PaGA) of disease activity for Sjögren's syndrome is performed using 3 separate scales: Visual Analog Scale (VAS) - an unnumbered 100 mm long horizontal line ranging from "very good' to "very poor". The assessment is made by placing a vertical mark across the line.; Numerical Rating Scale - a segmented numeric version of the VAS. A respondent needs to select a whole number (0-10 integers), with 0 being "very poor" and 10 being "very good".; 4-point Likert scale - The level of symptom severity is assessed on a scale from "none to severe".	48 weeks
Secondary	Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score at Week 48	Efficacy (Plan A and B); The Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F version 4) is a short, 13-item, easy-to-administer tool that measures an individual's level of fatigue during their usual daily activities over the past week (Webster et al 2003). The level of fatigue is measured on a 5-point Likert scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much).	48 weeks
Secondary	Proportion of patients achieving = 1 point or 15% reduction from baseline in EULAR Sjögren Syndrome Patient Reported Index (ESSPRI) at Week 48	Efficacy (Plan B); ESSPRI is an established disease outcome measure for Sjögren's (Seror et al 2011, Seror et al 2015). It consists of three domains of dryness, pain and fatigue.; The subject assesses severity of symptoms they experience on a single 0-10 numerical scale for each of the three domains. The ESSPRI score is defined as the mean of scores from the three scales: (dryness + pain + fatigue) /3. ESSPRI will be applied to the study patients at during runin period, at baseline and during study treatment.	48 weeks