Nipocalimab for Rheumatoid Arthritis

No longer recruiting at 41 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: IgG Fc-related therapeutics

Disqualifiers: Immunodeficiency, Malignancy, Asplenic, MI, others

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

Compensation: Varies

Number of Visits: 6

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the effectiveness and safety of nipocalimab, a new treatment for people with moderate to severe rheumatoid arthritis (RA). Participants will receive either nipocalimab or a placebo (a non-active treatment) alongside their usual care. The study seeks individuals diagnosed with RA who have had the condition for at least three months and experience ongoing symptoms like swollen and tender joints. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in RA treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are currently taking immunoglobulin (Ig)G fragment crystallizable (Fc)-related protein therapeutics, you may not be eligible to participate.

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

Research shows that nipocalimab is a monoclonal antibody designed to target specific substances in the body. It has been tested for safety in treating conditions like myasthenia gravis, a chronic muscle disease. Although limited information exists on its use for rheumatoid arthritis, previous studies suggest that treatments like nipocalimab are generally well-tolerated.

Reported side effects of nipocalimab are usually mild to moderate, including injection site reactions, headaches, and some nausea. Serious side effects are rare. This trial is in the mid-stage of testing, indicating some existing safety data, but more research is needed to confirm its safety for rheumatoid arthritis. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for RA?

Nipocalimab is unique because it targets a different pathway compared to most rheumatoid arthritis treatments. While traditional therapies often focus on suppressing inflammation or modulating the immune system broadly, nipocalimab works by blocking the neonatal Fc receptor (FcRn). This action prevents harmful antibodies from lingering in the bloodstream, potentially reducing inflammation and joint damage with more precision. Researchers are excited about nipocalimab because it offers a novel approach that might provide relief for patients who haven't responded well to existing treatments like methotrexate or TNF inhibitors.

What evidence suggests that nipocalimab might be an effective treatment for rheumatoid arthritis?

Research has shown that nipocalimab, which participants in this trial may receive, might help people with rheumatoid arthritis (RA). In studies, individuals with moderate to severe RA who used nipocalimab experienced noticeable improvements compared to those who did not. This treatment blocks a protein that causes inflammation, helping to reduce RA symptoms. Nipocalimab has also shown promise in treating other autoimmune diseases like Sjögren's disease, suggesting it can effectively lower disease activity. Overall, these findings provide hope that nipocalimab could be a helpful treatment for RA. ^{6 7 8 9 10}

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?

Inclusion Criteria

Diagnosis of rheumatoid arthritis (RA) and meeting the 2010 American college of rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for RA for at least 3 months before screening

Has moderate to severe active RA as defined by persistent disease activity with at least 6 swollen and 6 tender joints out of the 66/68-swollen and tender joint count at the time of screening and at baseline

Is positive for anti-citrullinated protein antibodies (ACPA) and/or rheumatoid factor (RF) at screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Up to 6 weeks

Treatment

Participants receive nipocalimab or placebo intravenously every 2 weeks for 12 weeks

12 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nipocalimab

How Is the Trial Designed?

Group I: Group 2: Nipocalimab Experimental Treatment 1 Intervention

Participants will receive nipocalimab IV q2w through Week 10 along with standard-of-care background therapy.

Group II: Group 1: Placebo Placebo Group 1 Intervention

Participants will receive placebo intravenously (IV) every 2 weeks (q2w) through Week 10 along with standard-of-care background therapy.

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

A new assay was developed to measure the uptake of IgG antibodies, including variants with stronger binding to the neonatal Fc receptor (FcRn), which could improve the safety and efficacy of antibody-drug conjugates (ADCs) by reducing toxicity from non-target uptake.

The study found that while a variant with enhanced FcRn binding showed increased uptake at lower pH levels, it also had similar uptake to wild type IgG at physiological pH (7.4), indicating the need for careful selection of variants to minimize toxicity in ADC applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reproducible quantification of IgG uptake at endogenous and overexpressed FcRn levels at pH 7.4: Comparison of a wild type IgG and a stronger FcRn binding variant. Zhang, J., Vernes, JM., Wen, X., et al.[2020]

Novel variants of therapeutic antibodies with specific amino acid substitutions in the Fc region can completely eliminate binding to Fc gamma receptors (FcγR) and C1q, reducing the risk of unwanted inflammatory responses.

These variants maintain important properties such as binding to FcRn, manufacturability, stability, and low potential for immunogenicity, suggesting they could enhance the safety and efficacy of therapeutic antibodies and fusion proteins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fc-engineered antibodies with immune effector functions completely abolished. Wilkinson, I., Anderson, S., Fry, J., et al.[2022]

In a study using wild-type and FcgammaR knock-out mice, the TA99 antibody significantly reduced lung metastases in metastatic melanoma, highlighting its efficacy in targeting the gp75 tumor antigen.

The study identified FcgammaRI (CD64) as the key receptor mediating the antitumor effects of TA99, and found that combining TA99 with the TLR-4 agonist MPL enhanced its protective effects, further emphasizing the importance of FcgammaRI in this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The high-affinity IgG receptor, FcgammaRI, plays a central role in antibody therapy of experimental melanoma. Bevaart, L., Jansen, MJ., van Vugt, MJ., et al.[2021]

The study developed three unique monoclonal antibodies (mAbs) that specifically target the inhibitory Fc gamma receptor II (FcγRIIB), which is crucial for regulating immune responses, particularly in the context of cancer therapy and autoimmunity.

These mAbs are categorized into agonistic, which activate FcγRIIB, and antagonistic, which block its activation, demonstrating distinct effects in biochemical and cellular assays, thus providing new tools for manipulating FcγRIIB in therapeutic settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and characterisation of monoclonal antibodies specific for the murine inhibitory FcγRIIB (CD32B). Williams, EL., Tutt, AL., French, RR., et al.[2012]

The neonatal Fc receptor (FcRn) is functionally expressed in human immune cells, including monocytes, macrophages, and dendritic cells, indicating a potential role in IgG transport and protection from degradation.

FcRn binds human IgG at acidic pH, suggesting it may have unique IgG binding functions in immune cells compared to traditional Fc gamma receptors, which could influence immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells. Zhu, X., Meng, G., Dickinson, BL., et al.[2022]

Fc gamma Receptor IIB (FcγRIIB) plays a crucial role in regulating immune responses, particularly in the context of immunotherapy, by inhibiting signals from other receptors like activatory FcγRs and the B cell receptor.

Recent studies suggest that FcγRIIB can enhance the effectiveness of certain immunomodulatory monoclonal antibodies (mAbs), indicating its potential as a therapeutic target to improve immunotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FcγRIIB as a key determinant of agonistic antibody efficacy. White, AL., Beers, SA., Cragg, MS.[2016]

Citations

1.

jnj.com

jnj.com/media-center/press-releases/published-in-the-lancet-nipocalimab-significantly-decreased-sjogrens-disease-sjd-activity-and-severity-through-substantial-reduction-in-sjogrens-related-autoantibodies

Nipocalimab significantly decreased Sjögren's disease ...

Nipocalimab, a first-in-class FcRn blocker being investigated for SjD, met its primary endpoint in the Phase 2 DAHLIAS study with ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38942592/

Nipocalimab, an anti-FcRn monoclonal antibody, in ...

Nipocalimab showed consistent, numerical efficacy benefits in participants with moderate to severe active RA, with greater benefit observed for participants ...

3.

neurologylive.com

neurologylive.com/view/newly-unveiled-epic-trial-pins-myasthenia-gravis-medications-nipocalimab-against-efgartigimod-efficacy

Newly Unveiled EPIC Trial Pins Myasthenia Gravis ...

In the data, revealed at the 2025 European Academy of Neurology Congress, nipocalimab displayed comparable onset of symptom relief at 1-week and ...

4.

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 ...

5.

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.

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2025/761430Orig1s000OtherR.pdf

761430Orig1s000 OTHER REVIEW(S) - accessdata.fda.gov

2020). Safety data are not currently available for nipocalimab exposure during pregnancy among females with gMG.5 In the Phase 3 pivotal ...

7.

medchemexpress.com

medchemexpress.com/nipocalimab.html?srsltid=AfmBOoq-ihajtjAKFRa61p5vZY6ZoOUQeVQuj8tyuIRwDSHecqDrartf

Nipocalimab (M281) | Anti-FcRn Antibody

Nipocalimab (M281) is a fully humanized, recombinant, and non-glycosylated IgG1 monoclonal antibody ... SAFETY DATA SHEET (SDS). English - EN (251 KB) Français - ...

8.

humimmu.com

humimmu.com/products/anti-human-fcrn-monoclonal-antibody-1

Anti-Human FcRn Monoclonal Antibody, Clone: Nipocalimab

Anti-Human FcRn Monoclonal Antibody, Clone: Nipocalimab ; Endotoxin: <1EU/mg ,Determined by LAL gel clotting assay ; Purity: >95% Determined by SDS-PAGE.

9.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04991753

NCT04991753 | A Proof-of-concept Study of the Efficacy ...

The purpose of this study is to evaluate the efficacy and safety of nipocalimab versus placebo in participants with moderate to severe active rheumatoid ...

10.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0003496724285113

AB0081 BIODISTRIBUTION OF NIPOCALIMAB (ANTI- ...

Nipocalimab (JNJ-80202135, M281) is a fully human IgG1 monoclonal antibody (mAb) designed to bind to the human FcRn receptor with high affinity at both ...