Nipocalimab in Moderate to Severe Sjögren's Syndrome (DAFFODIL)
Summary description of the study
Sjögren's syndrome (SJD) is a chronic (long-term), progressive autoimmune disease (the body's immune system attacks normal tissue), in which circulating immunoglobulin (IgG) autoantibodies activate the immune system, including B cells (a type of white blood cell known as lymphocytes). This leads to vascular damage and local destruction of the exocrine glands (glands that produce and secrete saliva, tears, etc.). This results in dry mouth, dry eyes, and vaginal dryness. SJD can also cause fatigue, pain, and problems with the skin, muscles, and internal organs (e.g., lungs, kidneys, brain, nerves). Currently approved treatments only alleviate the symptoms of dryness. Guidelines recommend broad-spectrum immunosuppressive therapy (treatment that reduces the activity of the body's immune system) for individuals with moderate to severe SJD. Nipocalimab (JNJ-80202135) is a monoclonal antibody* that selectively blocks the IgG binding site of the endogenous neonatal Fc receptor (FcRn). This leads to a reduction in circulating IgG concentration and thus a decrease in the inflammatory immune response to harmful IgG molecules in the body. *A type of protein designed to recognize and bind to a specific target. In this study, researchers want to investigate how well Nipocalimab works in participants with moderate to severe SJD compared to placebo. The study includes the following periods: screening phase (6 weeks), double-blind treatment phase (48 weeks), open-label long-term extension phase (96 weeks), and safety follow-up (6 weeks). The total duration of the study is approximately three years.
(BASEC)
Intervention under investigation
Participants will receive Nipocalimab subcutaneously (SC) or placebo along with standard treatments. At the week 48 visit, eligible participants from both studies will have the opportunity to participate in an open-label long-term extension phase (OLE). In this phase, they will receive Nipocalimab until week 143 or until the study intervention is discontinued and until they exit the study.
(BASEC)
Disease under investigation
Sjögren's Syndrome
(BASEC)
• Stable health status based on physical examination, medical history, vital signs, clinical laboratory tests, and a 12-lead electrocardiogram (ECG) at screening • Meets the diagnostic criteria for SJD according to the ACR/EULAR classification (American College of Rheumatology / European Alliance of Associations for Rheumatology) from 2016 • Seropositive for anti-Ro/SSA antibodies (Ro60 and/or Ro52) at screening • ClinESSDAI total score greater than or equal to (≥) 5 at screening • Female participants of childbearing potential must have a negative highly sensitive serum pregnancy test (Beta-hCG) at screening and a negative urine pregnancy test prior to randomization at week 0. (BASEC)
Exclusion criteria
• History of severe, progressive, and/or uncontrolled liver, gastrointestinal, kidney, lung, cardiovascular, psychiatric, neurological, musculoskeletal, or hypertensive diseases and/or other medical or uncontrolled autoimmune diseases or clinically significant abnormalities in laboratory tests • Known allergy, hypersensitivity, or intolerance to Nipocalimab or its excipients or the excipients used in the placebo formulation • Presence of a confirmed or suspected clinical immunodeficiency syndrome unrelated to the treatment of SJD, or a family history of congenital or hereditary immunodeficiencies • Previous reactions to therapeutic proteins (monoclonal antibodies, intravenous immunoglobulins, etc.) with severe immediate hypersensitivity, e.g., anaphylactic shock. • Unstable or progressive manifestation of SJD likely requiring therapeutic escalation beyond the approved baseline medications. (BASEC)
Trial sites
Basel
(BASEC)
Sponsor
Janssen-Cilag AG
(BASEC)
Contact
Contact Person Switzerland
Study Contact
+1 844 434 4210
Participate-In-This-Study1@clutterits.jnj.comJanssen-Cilag GmbH
(BASEC)
General Information
Janssen Research & Development, LLC
844-434-4210
Participate-In-This-Study1@clutterits.jnj.com(ICTRP)
General Information
Janssen Research & Development, LLC
(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee northwest/central Switzerland EKNZ
(BASEC)
Date of authorisation
10.12.2025
(BASEC)
ICTRP Trial ID
NCT06741969 (ICTRP)
Official title (approved by ethics committee)
A Randomized, Placebo-controlled, Double-blind, Multicenter Phase 3 Protocol to Assess the Efficacy and Safety of Nipocalimab in Adults with Moderate to Severe Sjögren's Disease (SjD) (BASEC)
Academic title
A Randomized, Placebo-controlled, Double-blind, Multicenter Phase 3 Protocol to Assess the Efficacy and Safety of Nipocalimab in Adults With Moderate to Severe Sjogren's Disease (SjD) (ICTRP)
Public title
Nipocalimab in Moderate to Severe Sjogren's Disease (ICTRP)
Disease under investigation
Sjogrens Syndrome (ICTRP)
Intervention under investigation
Drug: NipocalimabDrug: PlaceboDrug: Standard of care treatment (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Inclusion/Exclusion criteria
Inclusion Criteria:-
- Medically stable on the basis of physical examination, medical history, vital signs,
clinical laboratory tests, and 12-lead electrocardiogram (ECG) performed at
screening
- Meets criteria for diagnosis of SjD by the 2016 American College of
Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR)
classification criteria
- Seropositive for antibodies to Ro/SSA (Ro60 and/or Ro52) at screening
- Total ClinESSDAI score greater than or equal to (>=) 5 at screening
- Participants of childbearing potential must have a negative highly sensitive serum
(beta-hCG) pregnancy test at screening and a negative urine pregnancy test at Week 0
prior to randomization
Exclusion Criteria:
- Has a history of severe, progressive and/or uncontrolled hepatic, gastrointestinal,
renal, pulmonary, cardiovascular, psychiatric, neurological or musculoskeletal
disorder, hypertension, and/or any other medical or uncontrolled autoimmune disorder
or clinically significant abnormalities in screening laboratory
- Known allergies, hypersensitivity, or intolerance to nipocalimab or its excipients
or excipients used in the placebo formulation
- Has any confirmed or suspected clinical immunodeficiency syndrome not related to
treatment of his/her SjD or has a family history of congenital or hereditary
immunodeficiency
- Has shown a previous severe immediate hypersensitivity reaction, such as
anaphylaxis, to therapeutic proteins (for example [e.g.], monoclonal antibodies,
intravenous immunoglobulin)
- Has any unstable or progressive manifestation of SjD that is likely to warrant
escalation in therapy beyond permitted background medications (ICTRP)
not available
Primary and secondary end points
Change from Baseline in Clinical European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ClinESSDAI) Score at Week 48 (ICTRP)
Improvement from Baseline in Minimal Clinically Important Improvement (MCII) in ClinESSDAI Score at Week 48;Improvement from Baseline in ClinESSDAI Score at Week 48 in Participants with High Immunoglobulin (IgG) Levels at Baseline;Change from Baseline in ClinESSDAI Score at Week 8;Change from Baseline in Stimulated Salivary Flow Rate at Week 48;Change from Baseline in Sjogren's Symptoms Dryness Score at Week 48;Change from Baseline in Sjogren's Symptoms Joint Pain Score at Week 48;Change from Baseline in EULAR Sjogren's Syndrome Patient Reported Index (ESSPRI) Score At Week 48;Change from Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT) Fatigue Score at Week 48 (ICTRP)
Registration date
18.12.2024 (ICTRP)
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
Janssen Research & Development, LLC Clinical TrialStudy Contact, Participate-In-This-Study1@its.jnj.com, 844-434-4210, Janssen Research & Development, LLC (ICTRP)
Secondary trial IDs
80202135SJS3001, 2024-513965-38-00, 80202135SJS3001 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/study/NCT06741969 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available