A Study of Nipocalimab in Adults With Primary Sjogren's Syndrome (pSS)

Sjogren's Syndrome Clinical Trial

Official title:

A Randomized, Placebo-controlled, Double-blind, Multicenter Study to Assess the Efficacy and Safety of Nipocalimab in Adults With Primary Sjogren's Syndrome (pSS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04968912
• Other study ID #: CR109062
• Secondary ID: 2021-000665-3280
• Status: Completed
• Phase: Phase 2
• Start date: September 21, 2021
• Est. completion date: November 30, 2023

Study information

• Verified date: March 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of nipocalimab in participants with primary Sjogren's syndrome (pSS) versus placebo.

Description:

Sjogren's syndrome is a chronic, progressive autoimmune disease of unclear etiology typically originating in exocrine glands and capable of affecting the function of almost any organ system in the body. Nipocalimab is a fully human aglycosylated immunoglobulin (Ig)G1 monoclonal antibody designed to selectively bind, saturate, and block the IgG binding site on the endogenous neonatal fragment crystallizable receptor (FcRn). Nipocalimab blocks the binding site for IgG on FcRn, leads directly to increased IgG catabolism and a decrease in circulating IgG antibody concentrations, including pathogenic IgG antibody concentrations, and directly inhibits inflammatory cellular responses to these pathogenic IgG. Therefore, Nipocalimab may successfully treat pSS and improve disease manifestations. The study will consist of Screening Period (less than or equal to [<=] 6 Weeks), Double-blind Treatment Period (24 Weeks), and a Follow-up Period (6 Weeks). Key safety assessments will include adverse events (AEs), serious adverse events (SAEs), adverse events of special interests (AESIs), clinical laboratory safety tests (hematology, chemistry, urinalysis, and lipid profile) and vital signs. The total duration of the study is up to 36 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 163
• Est. completion date: November 30, 2023
• Est. primary completion date: October 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Meets classification criteria for primary Sjogren's syndrome (pSS) by the 2016 American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) at the time of screening, and was diagnosed with pSS no less than 26 weeks prior to screening

• At screening is seropositive for antibodies to pSS-associated antigen A (Ro/Sjogren's syndrome-related antigen A [SSA])

• Total Clinical European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (clinESSDAI) score greater than or equal to (>=) 6

• At least one abnormal laboratory marker of pSS-related inflammatory disease activity, and at least low activity in one or more specified European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) domains

• It is recommended that participants are up to date on all age-appropriate vaccinations prior to screening as per routine local medical guidelines. For study participants who received locally-approved (and including emergency use-authorized) coronavirus disease 2019 (COVID-19) vaccines recently prior to study entry, applicable local vaccine labelling, guidelines, and standards-of-care for participants receiving immune-targeted therapy will be followed when determining an appropriate interval between vaccination and study enrollment

Exclusion Criteria:

• Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her pSS or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant

• Comorbidities (for example, asthma, chronic obstructive pulmonary disease) which have required 3 or more courses of systemic glucocorticoids within the previous 12 months

• Has any unstable or progressive manifestation of pSS that is likely to warrant escalation in therapy beyond permitted background medications and/or has severely active pSS

• Has received oral cyclophosphamide within 3 months or intravenous (IV) cyclophosphamide within 6 months prior to first administration of study intervention

• Has Sjogren's syndrome overlap syndromes where another confirmed autoimmune rheumatic or systemic inflammatory condition (for example, rheumatoid arthritis [RA], systemic lupus erythematosus [SLE], scleroderma, inflammatory bowel disease [IBD]) is the primary diagnosis or has clinical manifestations that, in the opinion of the investigator, or the sponsor or sponsor's representative, are likely to interfere with the investigator's ability to assess pSS manifestations

Related Conditions & MeSH terms

• Sjogren's Syndrome
• Syndrome

Intervention

Other:
• Placebo
Placebo infusion will be administered intravenously.

Drug:
• Nipocalimab
Nipocalimab dose 1 and dose 2 infusions will be administered intravenously.
• Standard of Care Treatment
Standard of care treatment including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues, and/or one immunomodulator with or without low-dose glucocorticosteroids will be administered topically/orally.

Locations

Country	Name	City	State
France	CHU de Grenoble Hopital Albert Michallon	La Tronche
France	Centre Hospitalier Le Mans	le mans Cedex 9
France	Hopital Saint Joseph	Marseille Cedex 08
France	Hopital Pitie Salpetriere	Paris
France	CHRU Hôpital de Hautepierre	Strasbourg Cedex
Germany	Charite Universitatsmedizin Berlin	Berlin
Germany	Universitatsklinikum Carl Gustav Carus Dresden	Dresden
Germany	Hamburger Rheuma Forschungszentrum II	Hamburg
Germany	medius KLINIK KIRCHHEIM	Kirchheim unter Teck
Germany	Uniklinik Köln	Köln
Germany	Universitatsklinikum Tubingen	Tübingen
Italy	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia Presidio Spedali Civili	Brescia
Italy	P.O. Vittorio Emanuele Azienda Ospedaliero Universitaria 'Policlinico Vittorio Emanuele'	Catania
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone	Palermo
Italy	Azienda Ospedaliera Universitaria Integrata Verona	Verona
Japan	Tokyo Metropolitan Tama Medical Center	Fuchu
Japan	Nagasaki University Hospital	Nagasaki-shi
Japan	Hokkaido University Hospital	Sapporo-shi
Japan	Nihon University Itabashi Hospital	Tokyo
Japan	St. Luke's International Hospital	Tokyo
Japan	University of Tsukuba Hospital	Tsukuba-Shi
Netherlands	Medisch Centrum Leeuwarden	Leeuwarden
Netherlands	Erasmus Medisch Centrum	Rotterdam
Poland	Nasz Lekarz Przychodnie Medyczne	Bydgoszcz
Poland	Szpital Uniwersytecki nr 2 im dr Jana Biziela w Bydgoszczy	Bydgoszcz
Poland	Zespolu Opieki Zdrowotnej w Konskich	Konskie
Poland	Malopolskie Badania Kliniczne Sp z o o	Krakow
Poland	REUMED Zespol Poradni Specjalistycznych Filia nr 2	Lublin
Poland	Centrum Medyczne	Poznan
Poland	Medycyna Kliniczna	Warsaw
Poland	Narodowy Instytut Geriatrii Reumatologii i Rehabilitacji im prof dr hab med Eleonory Reicher	Warsaw
Poland	Centrum Medyczne AMED Targowek	Warszawa
Poland	Centrum Medyczne Oporow	Wroclaw
Portugal	Instituto Portugues de Reumatologia	Lisboa
Portugal	ULSAM, EPE - Hospital Conde de Bertiandos	Ponte de Lima
Spain	Hosp. Reina Sofia	Córdoba
Spain	Hosp. Univ. A Coruna	La Coruña
Spain	Hosp. de Merida	Mérida
Spain	Corporacio Sanitari Parc Tauli	Sabadell
Spain	Hosp. Clinico Univ. de Salamanca	Salamanca
Spain	Hosp. Infanta Luisa	Sevilla
Taiwan	Tri-Service General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital Linkou Branch	Taoyuan
United States	Anniston Medical Clinic	Anniston	Alabama
United States	Austin Regional Clinic	Austin	Texas
United States	Rheumatology Associates Of South Florida	Boca Raton	Florida
United States	Bay Area Arthritis and Osteoporosis	Brandon	Florida
United States	Trinity Clinical Research, LLC	Carrollton	Texas
United States	Columbia Arthritis Center	Columbia	South Carolina
United States	Colorado Arthritis Associates	Denver	Colorado
United States	Denver Arthritis Clinic	Denver	Colorado
United States	Altoona Center For Clinical Research	Duncansville	Pennsylvania
United States	St. Paul Rhuematology P A	Eagan	Minnesota
United States	Centre for Rheumatology, Immunology and Arthritis	Fort Lauderdale	Florida
United States	St. Jude Heritage Medical Group	Fullerton	California
United States	Arizona Arthritis and Rheumatology Research PLLC	Glendale	Arizona
United States	Clinical Investigation Specialists	Gurnee	Illinois
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	University of Florida Health Jacksonville	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Dr. Ramesh Gupta	Memphis	Tennessee
United States	Arizona Arthritis & Rheumatology Research, PLLC	Mesa	Arizona
United States	Omega Research Consultants	Orlando	Florida
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	PMG Research of Salisbury	Salisbury	North Carolina
United States	North Mississippi Medical Clinics	Tupelo	Mississippi
United States	Inland Rheumatology Clinical Trials, Inc.	Upland	California

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Japan,  Netherlands,  Poland,  Portugal,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline in Clinical European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (clinESSDAI) Score at Week 24	The clinESSDAI is a validated tool used in clinical studies to measure the systemic disease activity in participants with primary Sjogren's syndrome. The clinESSDAI includes 11 domains divided into 3-4 activity levels, where zero represents no activity and low, medium, and high scores can vary in numerical value depending on the domain.	Baseline to Week 24
Secondary	Change from Baseline in European League Against Rheumatism (EULAR) Sjogren Syndrome Patient Reported Index (ESSPRI) Score at Week 24	The ESSPRI is a patient-reported assessment of the severity of dryness, fatigue, and pain associated with primary Sjogren's Syndrome. Participants are asked to rate the severity of dryness, fatigue and pain over the past 2 weeks on a numeric rating scale (NRS), ranging from 0 "no symptoms (dryness, fatigue or pain)" to 10 "maximal imaginable (dryness, fatigue, pain)". A global score, calculated as the mean of the 3 domain scores, ranges from 0 to 10, with higher scores reflecting greater (worse) symptom severity.	Baseline to Week 24
Secondary	Improvement of Greater than or Equal to (>=) 4 Points from Baseline in ESSDAI Score (Minimal Clinically Important Improvement) at Week 24	The ESSDAI is a validated tool used in clinical studies to measure the systemic disease activity in participants with primary Sjogren's syndrome. The ESSDAI includes 11 to 12 domains divided into 3-4 activity levels, where zero represents no activity and low, medium, and high scores can vary in numerical value depending on the domain.	Baseline to Week 24
Secondary	Improvement of >= 4 Points from Baseline in clinESSDAI Score (Minimal Clinically Important Improvement) at Week 24	The clinESSDAI is a validated tool used in clinical studies to measure the systemic disease activity in participants with Sjogren's syndrome. A minimal clinically important improvement in clinESSDAI is defined as a decrease of at least 4 points in the composite clinESSDAI score.	Baseline to Week 24
Secondary	ESSPRI Response at Week 24	ESSPRI response defined as a decrease of one point or a decrease of >= 15 percent (%) from baseline (minimal clinically important improvement) at Week 24 will be reported.	Week 24
Secondary	Disease Response as Assessed by Sjögren's Tool for Assessing Response (STAR) Composite Score at Week 24	Disease response by STAR of >= 5 at Week 24 will be reported. STAR is a composite tool that incorporates measures of disease activity (clinESSDAI), symptoms (ESSPRI), glandular function and systemic disease activity biomarkers to assess disease activity.	Week 24
Secondary	Improvement in Disease Activity Level by >= 1 Level in at Least One clinESSDAI or ESSDAI Domain at Week 24	Improvement in disease activity level by >= 1 level in at least one clinESSDAI or ESSDAI domain (biological, hematological, cutaneous, constitutional, lymphadenopathy and lymphoma, and glandular) at Week 24 will be reported.	Week 24
Secondary	Improvement from Baseline in >= 3 of 5 Composite of Relevant Endpoints for Sjogren's Syndrome (CRESS) Categories at Week 24	Improvement from baseline in >= 3 of 5 CRESS categories at week 24 will be reported. CRESS is a composite tool that incorporates measures of disease activity (clinESSDAI), symptoms (ESSPRI), glandular function and systemic inflammation to assess disease activity.	Baseline to Week 24
Secondary	Percentage of Participants with Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment.	Up to 30 weeks
Secondary	Percentage of Participants with Adverse Events of Special interests (AESIs)	Percentage of participants with AESIs will be reported. Treatment-emergent adverse events associated with the following situations are considered as AESIs: severe infections, severe hypoalbuminemia or hypogammaglobulinemia.	Up to 36 weeks
Secondary	Percentage of Participants with Treatment-emergent Serious Adverse Events (SAEs)	Treatment-emergent SAEs are defined as SAEs with onset or worsening on or after date of first dose of study treatment.	Up to 30 weeks
Secondary	Percentage of Participants with TEAEs Leading to Treatment Discontinuation	Percentage of participants with TEAEs leading to treatment discontinuation will be reported. TEAEs are defined as AEs with onset or worsening on or after date of first dose of study treatment.	Up to 30 weeks
Secondary	Percentage of Participants with Clinically Significant Abnormalities in Vital Signs	Percentage of participants with clinically significant abnormalities in vital signs (including temperature, pulse/heart rate, respiratory rate, and blood pressure) through end of study visit will be reported.	Up to 36 weeks
Secondary	Percentage of Participants with Clinically Significant Abnormalities in Laboratory Parameters	Percentage of participants with clinically significant abnormalities in laboratory parameters (including hematology, blood chemistry, urinalysis, and blood coagulation) through end of study visit will be reported.	Up to 36 weeks
Secondary	Serum Concentration of Nipocalimab Over Time	Serum concentrations of nipocalimab over time in participants receiving active study intervention will be reported.	Up to Week 30
Secondary	Number of Participants with Antibodies to Nipocalimab (Anti-drug Antibodies [ADAs] and Neutralizing Antibodies [NAbs])	Number of participants with antibodies to nipocalimab (ADAs and NAbs) in participants receiving active study intervention will be reported.	Up to Week 36
Secondary	Number of Participants with Change from Baseline in Biomarkers	Number of participants with change from baseline in biomarkers (C-reactive protein [CRP], erythrocyte, total immunoglobulin [Ig]G, IgG1, IgG2, IgG3, IgG4) will be reported.	Baseline to Week 36
Secondary	Number of Participants with Change from Baseline in Autoantibodies	Number of participants with change from baseline in autoantibodies (anti-Sjogren's syndrome related antigen A (anti-Ro/SSA), anti-Sjogren's syndrome related antigen B (anti-La/SSB), rheumatoid factor [RF] and antinuclear antibody [ANA]) will be reported.	Baseline to Week 36