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

Sjogren Syndrome Clinical Trial

— NEPTUNUS-1  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05350072
• Other study ID #: CVAY736A2301
• Secondary ID: 2020-005661-14
• Status: Recruiting
• Phase: Phase 3
• Start date: July 28, 2022
• Est. completion date: March 9, 2028

Study information

• Verified date: May 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, 2-arm multicenter phase 3 study to assess the efficacy and safety of ianalumab in patients with active Sjogren's syndrome (NEPTUNUS-1)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 268
• Est. completion date: March 9, 2028
• Est. primary completion date: March 6, 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 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.

Related Conditions & MeSH terms

• Sjogren Syndrome
• Sjogren's Syndrome
• Syndrome

Intervention

Biological:
• VAY736
ianalumab s.c.

Other:
• Placebo
placebo s.c.

Locations

Country	Name	City	State
Austria	Novartis Investigative Site	Graz
Austria	Novartis Investigative Site	Stockerau
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Leuven
Brazil	Novartis Investigative Site	Juiz de Fora	MG
Brazil	Novartis Investigative Site	Ribeirao Preto	SP
Brazil	Novartis Investigative Site	Rio de Janeiro
Brazil	Novartis Investigative Site	Sao Paulo
Brazil	Novartis Investigative Site	Vitoria	ES
Chile	Novartis Investigative Site	Santiago
Chile	Novartis Investigative Site	Santiago
China	Novartis Investigative Site	Baotou	Inner Mongolia
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Guangzhou
China	Novartis Investigative Site	Hohhot	Inner Mongolia
China	Novartis Investigative Site	Linyi	Shandong
China	Novartis Investigative Site	Nanchang	Jiangxi
China	Novartis Investigative Site	Shanxi
China	Novartis Investigative Site	Shenyang	Liaoning
China	Novartis Investigative Site	Shenzhen	Guangdong
China	Novartis Investigative Site	Taiyuan	Shanxi
China	Novartis Investigative Site	Wuhan	Hubei
Czechia	Novartis Investigative Site	Brno
Czechia	Novartis Investigative Site	Praha 11
Czechia	Novartis Investigative Site	Uherske Hradiste
France	Novartis Investigative Site	Caen Cedex 9
France	Novartis Investigative Site	Dijon
France	Novartis Investigative Site	Grenoble
France	Novartis Investigative Site	Lille
France	Novartis Investigative Site	Marseille
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Paris 13
France	Novartis Investigative Site	Paris cedex 10
France	Novartis Investigative Site	Saint Etienne
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Gommern
Germany	Novartis Investigative Site	Ludwigshafen
Germany	Novartis Investigative Site	Wuerzburg
Guatemala	Novartis Investigative Site	Guatemala
Guatemala	Novartis Investigative Site	Guatemala
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Quetzaltenango
Korea, Republic of	Novartis Investigative Site	Daegu
Korea, Republic of	Novartis Investigative Site	Gwangju
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Lithuania	Novartis Investigative Site	Vilnius
Mexico	Novartis Investigative Site	Ciudad de Mexico	Distrito Federal
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Poland	Novartis Investigative Site	Bydgoszcz
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Wroclaw	Dolnoslaskie
Portugal	Novartis Investigative Site	Braga
Portugal	Novartis Investigative Site	Guarda
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Badalona	Catalunya
Spain	Novartis Investigative Site	Bilbao	Pais Vasco
Spain	Novartis Investigative Site	La Coruna	Galicia
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Sabadell	Barcelona
Spain	Novartis Investigative Site	Sevilla	Andalucia
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Kocaeli
United States	The John Hopkins Jerome L Greene	Baltimore	Maryland
United States	Ochsner Health System	Baton Rouge	Louisiana
United States	Reciomed Clinical Research	Boynton Beach	Florida
United States	Rush University Medical Center Suite 300	Chicago	Illinois
United States	Precision Comprehensive Research	Colleyville	Texas
United States	Prisma Health Rheumatology	Columbia	South Carolina
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dallas	Texas
United States	STAT Research Inc .	Dayton	Ohio
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Baylor College Of Medicine .	Houston	Texas
United States	Indiana Univ School of Dentistry	Indianapolis	Indiana
United States	Houston Rheumatology & Arthrit Houston Rheum and Arthritis	Katy	Texas
United States	Winthrop University Hospital	Mineola	New York
United States	Arizona Arthritis and Rheumatology Associates PLLC .	Paradise Valley	Arizona
United States	West Broward Rheumatology Assoc Inc	Tamarac	Florida
United States	Medvin Clinical Research .	Van Nuys	California
United States	Carolina Arthritis Associates	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Brazil,  Chile,  China,  Czechia,  France,  Germany,  Guatemala,  Korea, Republic of,  Lithuania,  Mexico,  Poland,  Portugal,  Singapore,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of Treatment Emergent Adverse Event (TEAEs)/Serious Adverse Events (SAEs) 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) up 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 end of study)	Pharmacokinetics (Plan A and B)	through study completion up to 2 years
Primary	Change from baseline in EULAR Sjogren 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); 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.	24 weeks
Secondary	Proportion of patients achieving meaningful improvement in 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)	48 weeks
Secondary	Change from baseline in Physician's Global Assessment (PhGA) of disease activity at Week 48	Efficacy (Plan A and B)	48 weeks
Secondary	Change from baseline in Patient's Global Assessment (PaGA) of disease activity at Week 48	Efficacy (Plan A and B)	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)	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)	48 weeks