Nipocalimab for Sjogren's Syndrome

(DAFFODIL Trial)

Recruiting at 43 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Uncontrolled autoimmune, Cardiovascular, Hepatic, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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).

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.

How is the drug Nipocalimab unique in treating Sjogren's Syndrome?

Nipocalimab is unique because it is an anti-FcRn monoclonal antibody, which works by blocking the FcRn receptor to reduce the levels of harmful antibodies in the body, potentially offering a new approach for treating Sjogren's Syndrome compared to traditional therapies that may not target this specific mechanism. ^{1 2 3 4 5}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Nipocalimab (Monoclonal Antibodies)

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.

Participant Groups

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+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Fc-gamma receptor III shedding by polymorphonuclear cells in primary Sjögren's syndrome. [2019]

2. England 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. [2015]

3. England 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. [2020]

4. Canada pubmed.ncbi.nlm.nih.gov

The presence of anti-Fc gamma receptor autoantibodies is related to the clinical presentation of primary Sjögren's syndrome. [2004]

5. Canada 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. [2022]