Nipocalimab for Sjogren's Syndrome

Recruiting at 95 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: Cyclophosphamide

Disqualifiers: Asthma, COPD, RA, SLE, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

163 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing nipocalimab, a medicine that targets harmful immune proteins, in people with primary Sjogren's syndrome. The goal is to see if it can reduce inflammation and improve symptoms in these patients.

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, if you have taken oral cyclophosphamide in the last 3 months or intravenous cyclophosphamide in the last 6 months, you may not be eligible to participate.

How is the drug Nipocalimab different from other treatments for Sjogren's Syndrome?

Nipocalimab is unique because it is an anti-FcRn monoclonal antibody, which means it works by blocking a specific receptor involved in the immune system, potentially reducing harmful antibodies. This mechanism is different from other treatments that may target B cells or other immune pathways. ^{1 2 3 4 5}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Exclusion Criteria

You have another autoimmune condition like rheumatoid arthritis, lupus, scleroderma, or inflammatory bowel disease that could make it difficult to accurately evaluate your symptoms of Sjogren's syndrome.

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 6 weeks

Treatment

Participants receive either nipocalimab or placebo intravenously every 2 weeks for 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Treatment Details

Interventions

• Nipocalimab
• Placebo
• Standard of Care Treatment

Participant Groups

Group I: Group 3: Nipocalimab Dose 2 Experimental Treatment 2 Interventions

Participants will receive nipocalimab dose 2 IV q2w through Week 22 along with standard of care treatments (\[including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues\], and/or one immunomodulator with or without low-dose glucocorticosteroids).

Group II: Group 2: Nipocalimab Dose 1 Experimental Treatment 2 Interventions

Participants will receive nipocalimab dose 1 IV q2w through Week 22 along with standard of care treatments (\[including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues\], and/or one immunomodulator with or without low-dose glucocorticosteroids).

Group III: Group 1: Placebo Placebo Group 2 Interventions

Participants will receive placebo intravenously (IV) every 2 weeks (q2w) through Week 22 along with standard of care treatments (\[including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues\], and/or one immunomodulator with or without low-dose glucocorticosteroids).

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]