A Proof-of-concept Study of the Efficacy and Safety of Nipocalimab in Participants With Active Rheumatoid Arthritis

Recruiting at 37 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

53 Participants Needed

Trial Summary

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.

What evidence supports the effectiveness of the drug Nipocalimab?

Research shows that blocking FcRn in humans can reduce levels of IgG (a type of antibody) and inhibit immune responses related to IgG, which is promising for treating autoimmune diseases. Nipocalimab, as an anti-FcRn monoclonal antibody, may work similarly by lowering harmful antibodies in the body. ^{1 2 3 4 5}

Is Nipocalimab (also known as M281, JNJ 80202135, or Anti-FcRn monoclonal antibody) generally safe for humans?

The research does not provide specific safety data for Nipocalimab, but it discusses the safety potential of Fc-engineered antibodies, which are designed to avoid unwanted inflammatory responses. This suggests that such antibodies, including those like Nipocalimab, may have improved safety profiles. ^{2 6 7 8 9}

How does the drug Nipocalimab differ from other treatments for autoimmune conditions?

Nipocalimab is unique because it targets the neonatal Fc receptor (FcRn), which is responsible for protecting immunoglobulin G (IgG) from degradation. By blocking FcRn, Nipocalimab reduces circulating IgG levels, potentially offering a novel approach to treating autoimmune diseases where IgG plays a role. ^{5 10 11 12 13}

What is the purpose of this trial?

This trial tests a new medicine on people with moderate to severe rheumatoid arthritis. It aims to reduce inflammation and joint damage in those who may not respond well to other treatments.

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

Interventions

• Nipocalimab

Participant Groups

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+

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

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]

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]

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]

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]

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 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Cutting edge: FcγRIII (CD16) and FcγRI (CD64) are responsible for anti-glycoprotein 75 monoclonal antibody TA99 therapy for experimental metastatic B16 melanoma. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

FcγRIIB as a key determinant of agonistic antibody efficacy. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Utility of neutrophil Fcγ receptor I (CD64) index as a biomarker for mucosal inflammation in pediatric Crohn's disease. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Association of FCGR2A with the response to infliximab treatment of patients with rheumatoid arthritis. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Blocking FcRn in humans reduces circulating IgG levels and inhibits IgG immune complex-mediated immune responses. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Fc-engineered antibodies with immune effector functions completely abolished. [2022]

7. Netherlands 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. [2020]

8. Germany pubmed.ncbi.nlm.nih.gov

Development and characterisation of monoclonal antibodies specific for the murine inhibitory FcγRIIB (CD32B). [2012]

9. Japan pubmed.ncbi.nlm.nih.gov

[Nonclinical Evaluation of Next-generation Therapeutic Monoclonal Antibodies]. [2017]

10. United States pubmed.ncbi.nlm.nih.gov

Human neutrophils express low levels of FcγRIIIA, which plays a role in PMN activation. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

The high-affinity IgG receptor, FcgammaRI, plays a central role in antibody therapy of experimental melanoma. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

The Fc receptor for IgG on human natural killer cells: phenotypic, functional, and comparative studies with monoclonal antibodies. [2007]