Nipocalimab for Sjogren's Syndrome

(DAFFODIL Trial)

Recruiting at 262 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Uncontrolled autoimmune, Cardiovascular, Hepatic, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness and safety of a new treatment called nipocalimab, an anti-FcRn monoclonal antibody, for people with moderate to severe Sjogren's syndrome, a condition that causes dry eyes and mouth. Participants will receive either nipocalimab or a placebo, which is a harmless substance resembling the drug, along with their usual care. Individuals diagnosed with Sjogren's syndrome, who have specific antibodies linked to the disease and experience significant symptoms, might be a good fit for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have any unstable or progressive symptoms that require more treatment than allowed by the study, which might imply some restrictions on medication changes.

Is there any evidence suggesting that nipocalimab is likely to be safe for humans?

Research has shown that nipocalimab has been tested in people with moderate to severe Sjogren's syndrome. In earlier studies, nipocalimab improved symptoms of the disease, and most participants tolerated the treatment well. The studies did not identify any major safety concerns, although some mild side effects like headaches and tiredness were reported. This suggests that nipocalimab could be a safe option for many with this condition. However, individual reactions can differ. It is important to consult a healthcare provider about potential risks and benefits before deciding to join a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Sjogren's?

Nipocalimab is unique because it offers a novel approach for treating Sjogren's Syndrome by targeting the FcRn receptor, which plays a key role in regulating antibodies in the body. Unlike standard treatments like hydroxychloroquine or pilocarpine, which primarily manage symptoms, nipocalimab aims to modulate the immune system more precisely. Researchers are excited about this treatment because it has the potential to not only alleviate symptoms but also address the underlying causes of the disease, potentially improving patients' quality of life significantly.

What evidence suggests that nipocalimab might be an effective treatment for Sjogren's?

Research has shown that nipocalimab, a new type of treatment, has potential in treating Sjogren's Syndrome. In this trial, participants will receive either nipocalimab or a placebo, both administered subcutaneously along with standard care treatments. Previous studies demonstrated that nipocalimab significantly reduced the disease's activity and severity by lowering harmful proteins that attack the body. Specifically, participants who received this treatment showed notable improvements compared to those who received a placebo. These findings suggest that nipocalimab could effectively manage symptoms of Sjogren's Syndrome. ^{5 6 7 8 9}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for people with moderate to severe Sjogren's disease, a condition where the immune system attacks glands that make tears and saliva. Participants should meet specific health criteria set by the study.

Inclusion Criteria

* Medically stable on the basis of physical examination, medical history, vital signs, 12-lead electrocardiogram (ECG) and clinical laboratory tests 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 at screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nipocalimab or placebo subcutaneously along with standard of care treatments

48 weeks

Regular visits as per study protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Eligible participants may opt into continuation of nipocalimab treatment until Week 143

Up to 95 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nipocalimab

Trial Overview The trial is testing nipocalimab, an experimental medication against Sjogren's disease. It compares its effectiveness and safety to a placebo (a substance with no active drug) and standard treatments currently used.

How Is the Trial Designed?

Group I: Nipocalimab Experimental Treatment 2 Interventions

Participants will receive nipocalimab subcutaneously (SC) along with standard of care treatments. At the Week 48 visit, eligible participants from both studies will have the option to enter an open-label long-term extension (OLE) phase, where they will continue to receive nipocalimab until Week 143 or until the study intervention is discontinued and participants opt to withdraw from the study.

Group II: Placebo Placebo Group 2 Interventions

Participants will receive placebo subcutaneously along with standard of care treatments. At the Week 48 visit, eligible participants from both studies will have the option to enter an OLE phase, where they will receive nipocalimab until Week 143 or until the study intervention is discontinued and participants opt to withdraw from the study.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

In a study of 66 patients with primary Sjögren's syndrome, 45% had autoantibodies against cell-free Fc-gamma receptor IIIb, indicating an immune response linked to the disease.

The presence of these autoantibodies suggests that they are produced after the activation and shedding of Fc-gamma receptor IIIb from polymorphonuclear leukocytes, potentially triggered by IgG-containing immune complexes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Fc gamma receptor autoantibodies from patients with Sjögren's syndrome do not react with native receptor on human polymorphonuclear leukocytes. Lamour, A., Le Corre, R., Soubrane, C., et al.[2015]

In a study of 350 patients, the combination of anti-α-fodrin antibodies (AFA) with rheumatoid factor (RF) or antinuclear antibodies (ANA) proved to be a useful alternative for diagnosing Sjögren syndrome (SS) in patients who tested negative for anti-Ro/La antibodies.

Using AFA alongside RF or ANA improved the sensitivity of SS diagnosis from 56.9% to 70.7%, indicating that these combinations can enhance diagnostic accuracy, although this came with a decrease in specificity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usefulness of IgA Anti-α-fodrin Antibodies in Combination with Rheumatoid Factor and/or Antinuclear Antibodies as Substitute Immunological Criterion in Sjögren Syndrome with Negative Anti-SSA/SSB Antibodies. Hernández-Molina, G., Nuñez-Alvarez, C., Avila-Casado, C., et al.[2022]

In a study of 66 patients with primary Sjögren's syndrome and 44 healthy controls, anti-Fc gamma RIII autoantibodies were detected, with a higher frequency in patients experiencing complications like nonerosive arthritis and lung involvement.

The presence of these autoantibodies may worsen the handling of immune complexes in patients with Sjögren's syndrome, particularly in those sharing the HLA-DR3 alloantigen, suggesting a potential mechanism for disease exacerbation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The presence of anti-Fc gamma receptor autoantibodies is related to the clinical presentation of primary Sjögren's syndrome. Lamour, A., Le Corre, R., Pennec, YL., et al.[2004]

A new sandwich enzyme-linked immunosorbent assay successfully detected Fc-gamma receptor III (Fc gamma RIII) in the serum of 8 out of 23 patients with primary Sjögren's syndrome, indicating its potential role in this condition.

Patients with Sjögren's syndrome showed a lower proportion of Fc gamma RIII-carrying polymorphonuclear (PMN) cells and impaired PMN functions, such as reduced adherence and chemotaxis, suggesting that the release of Fc gamma RIII may contribute to the inefficiency of immune responses in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fc-gamma receptor III shedding by polymorphonuclear cells in primary Sjögren's syndrome. Lamour, A., Soubrane, C., Ichen, M., et al.[2019]

Ianalumab (VAY736) demonstrated significant efficacy in reducing disease activity in patients with active primary Sjögren's syndrome, as shown by improvements in multiple clinical outcomes compared to placebo, including the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI).

The treatment resulted in rapid and sustained B cell depletion after a single infusion, with mild to moderate infusion reactions being the main side effects, indicating a favorable safety profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of primary Sjögren's syndrome with ianalumab (VAY736) targeting B cells by BAFF receptor blockade coupled with enhanced, antibody-dependent cellular cytotoxicity. Dörner, T., Posch, MG., Li, Y., et al.[2020]

Citations

1. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)01430-8/fulltext

Efficacy and safety of nipocalimab in patients with ... Exploratory efficacy outcomes were generally similar between nipocalimab 5 mg/kg and placebo. No data are available regarding the direct effects ...

2. investor.jnj.com investor.jnj.com/investor-news/news-details/2025/Published-in-The-Lancet-Nipocalimab-significantly-decreased-Sjgrens-disease-SjD-activity-and-severity-through-substantial-reduction-in-Sjgrens-related-autoantibodies/default.aspx

Nipocalimab significantly decreased Sjögren's disease (SjD ... Nipocalimab, a first-in-class FcRn blocker being investigated for SjD, met its primary endpoint in the Phase 2 DAHLIAS study with ...

3. ard.bmj.com ard.bmj.com/content/83/Suppl_1/240.2

LBA0010 EFFICACY AND SAFETY OF NIPOCALIMAB, AN ... DAHLIAS is the first study of a FcRn blocker in SjD and shows that nipocalimab treatment led to significant improvement over placebo in clinESSDAI.

4. academic.oup.com academic.oup.com/rheumatology/article/64/Supplement_3/keaf142.025/8115100

OA25 Efficacy and safety of nipocalimab, an anti-FcRn ... OA25 Efficacy and safety of nipocalimab, an anti-FcRn monoclonal antibody, in primary Sjogren's disease: results from a Phase 2, multicenter ...

5. acrabstracts.org acrabstracts.org/abstract/efficacy-and-safety-of-nipocalimab-an-anti-fcrn-monoclonal-antibody-in-primary-sjogrens-disease-results-from-a-phase-2-multicenter-randomized-placebo-controlled-double-blind-study-dah/

Efficacy and Safety of Nipocalimab, an Anti-FcRn ... The first study of a FcRn blocker in SjD, showed that nipocalimab led to significant improvement vs PBO in clinESSDAI and similar trends in other key efficacy ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06741969

Nipocalimab in Moderate to Severe Sjogren's Disease The purpose of this study is to evaluate the clinical efficacy and safety of nipocalimab in participants with moderate to severe Sjogren's disease (SjD).

7. jnjmedicalconnect.com jnjmedicalconnect.com/media/attestation/congresses/immunology/2025/rhapp/efficacy-and-safety-of-nipocalimab-an-antifcrn-monoclonal-antibody-in-primary-sjogrens-disease-resul.pdf

Efficacy and Safety of Nipocalimab, an Anti-FcRn ... Efficacy and Safety of Nipocalimab, an Anti-FcRn Monoclonal Antibody, in. Primary Sjögren's Disease: Results From a Phase 2, Multicenter, Randomized,. Placebo ...

8. isrctn.com isrctn.com/pdf/14534389

Nipocalimab in moderate to severe Sjogren's disease In this study, researchers want to learn how well nipocalimab works and how safe it is in participants with moderate to severe SjD compared to ...

9. jnj.com jnj.com/media-center/press-releases/nipocalimab-demonstrates-significant-clinical-improvement-in-disease-activity-and-igg-reduction-in-phase-2-sjogrens-disease-study

Nipocalimab demonstrates significant clinical improvement ... Nipocalimab demonstrates significant clinical improvement in disease activity and IgG reduction in Phase 2 Sjögren's disease study. Adults with ...