Nipocalimab for CIDP

Recruiting at 156 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Janssen Research & Development, LLC

Must be taking: Corticosteroids

Disqualifiers: Severe hepatic, Diabetes, Hypertension, others

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

Compensation: Varies

Number of Visits: 4

201 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called nipocalimab (an anti-FcRn monoclonal antibody) for people with chronic inflammatory demyelinating polyneuropathy (CIDP), a condition affecting the nerves that can cause weakness and numbness. Researchers aim to determine if nipocalimab can prevent symptoms from returning after initial improvement. The trial compares nipocalimab to a placebo to assess its impact. It may suit adults with CIDP who experience ongoing or returning symptoms and are currently on treatments like corticosteroids or immunoglobulins, or who have recently stopped these treatments.

As a Phase 2, Phase 3 trial, this study focuses on measuring the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to significant advancements in CIDP treatment.

Will I have to stop taking my current medications?

If you are currently treated with certain medications like intravenous or subcutaneous immunoglobulin, you will need to stop them by the run-in baseline visit. If you are on oral corticosteroids over 20 mg/day, you must reduce the dose to 20 mg/day or less during the run-in period.

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

Research has shown that nipocalimab has been tested for safety in treating conditions like generalized myasthenia gravis (gMG). In these studies, nipocalimab significantly lowered levels of harmful autoantibodies, proteins that mistakenly attack the body's own cells. This suggests it might help manage similar immune-related conditions.

Regarding safety, participants generally tolerated the treatment well. Common side effects included headaches and reactions at the infusion site, mostly mild. Serious side effects were rare.

Since the current study is in advanced stages, earlier studies have likely provided some evidence of safety in humans. Nipocalimab is also under investigation for other conditions, often indicating a good safety profile, although research continues for CIDP specifically. Participants should consult healthcare providers to understand personal risks and benefits before joining a trial. ^{1 2 3 4 5}

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

Nipocalimab is unique because it targets a specific part of the immune system called the FcRn receptor, which plays a role in regulating antibodies. Unlike standard treatments for Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), such as corticosteroids and intravenous immunoglobulin (IVIG), which broadly suppress the immune system, nipocalimab offers a more targeted approach. Researchers are excited about this treatment because it has the potential to provide effective symptom relief while minimizing some of the side effects associated with current therapies. Additionally, nipocalimab's method of action could lead to more sustained improvements for patients.

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

Research has shown that nipocalimab may help treat chronic inflammatory demyelinating polyneuropathy (CIDP). In this trial, participants will receive either nipocalimab or a placebo. Studies indicate that patients who took nipocalimab alongside their usual care managed their disease better than those who took a placebo. Specifically, they experienced fewer flare-ups and maintained a more stable condition. The treatment targets the immune responses responsible for nerve damage in CIDP. Early results suggest that nipocalimab could delay the return of symptoms for those who initially respond well to it. ^{4 5 6 7 8}

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?

Adults over 18 with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) as per EAN/PNS criteria, showing active disease. They must have an INCAT disability score of 2-9 and be willing to stop or taper current treatments like corticosteroids or immunoglobulins. Excluded are those with severe disorders, pure sensory CIDP, other diseases that explain symptoms better, known allergies to nipocalimab or its components.

Inclusion Criteria

Other protocol-defined inclusion criteria will apply

I am on low-dose steroids, willing to adjust my treatment, or have not started treatment.

I have been diagnosed with CIDP that is getting worse or coming back.

Exclusion Criteria

I do not have severe health issues that could affect my participation in the study.

I have been diagnosed with a specific type of chronic nerve disorder.

My symptoms are not caused by another disease like a stroke or lupus.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 4 weeks

Run-in

Participants with active CIDP undergo a run-in period to assess initial response

up to 12 weeks

Open-label Treatment (Stage A)

Participants receive open-label nipocalimab to assess clinical improvement

12 weeks

IV infusion every 2 weeks

Double-blind, Placebo-controlled Withdrawal (Stage B)

Participants are randomized to receive either nipocalimab or placebo to evaluate relapse prevention

up to 52 weeks

IV infusion every 2 weeks

Open-label Extension (OLE)

Participants may continue receiving nipocalimab until 2 years after marketing authorization or commercial availability

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nipocalimab

Trial Overview The trial is testing the effectiveness of Nipocalimab in preventing relapse in adults with CIDP who responded initially to the drug during Stage A. Participants will either receive Nipocalimab or a placebo to compare outcomes.

How Is the Trial Designed?

Group I: Nipocalimab Experimental Treatment 1 Intervention

Participants in Stage A (Open-label) will receive a loading dose of nipocalimab (Dose 1) intravenous (IV) infusion on Day 1, followed by nipocalimab (Dose 2) IV infusion once every 2 weeks (q2w) from Week 2 to Week 12. Participants who demonstrate evidence of clinical improvement in Stage A (responders) will enter Stage B (Double-blind) and receive nipocalimab (Dose 2) IV infusion q2w starting on Day 1 up to Week 52. After completion of Stage B or discontinuation from Stage B due to relapse, participants will have the option to enter the open label extension (OLE) phase and receive nipocalimab (Dose 2) IV infusion q2w starting on OLE Day 1 until 2 years after marketing authorization in a participant's local country or until nipocalimab becomes available commercially or via other continued access program, whichever comes first.

Group II: Placebo Placebo Group 1 Intervention

Participants receiving nipocalimab in Stage A and who demonstrate evidence of clinical improvement in Stage A (responders) will enter Stage B (Double-blind) and receive placebo IV infusion q2w starting on Day 1 up to Week 52. After completion of Stage B or discontinuation from Stage B due to relapse, participants will have the option to enter the open label extension (OLE) phase and receive nipocalimab (Dose 2) IV infusion q2w starting on OLE Day 1 until 2 years after marketing authorization in a participant's local country or until nipocalimab becomes available commercially or via other continued access program, whichever comes first.

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

Low dose rituximab (100 mg weekly for 4 weeks, then monthly) significantly improved clinical function scores in patients with treatment-resistant chronic inflammatory demyelinating polyneuropathy (CIDP) with anti-NF-155 antibodies over a 6-month follow-up period.

The treatment mechanism involves effective B cell depletion, leading to a decrease in certain B cell subsets associated with disease severity, while promoting the reestablishment of regulatory B cells, which may help in managing the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of low dose rituximab in treatment-resistant CIDP with antibodies against NF-155. Jiao, L., Xiang, Y., Li, S., et al.[2020]

A 14-year-old boy with treatment-resistant pediatric CIDP was found to have anti-neurofascin 155 antibodies, highlighting the importance of testing for these antibodies in similar cases.

The patient showed significant improvement after being treated with Rituximab, suggesting that this treatment may be effective for pediatric CIDP patients with specific antibody profiles who do not respond to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autoantibodies to a Nodal Isoform of Neurofascin in Pediatric Chronic Inflammatory Demyelinating Polyneuropathy. Chauvet, E., Blanchard Rohner, G., Manel, V., et al.[2023]

The study successfully developed three monoclonal antibodies that can distinguish between different isoforms of the Fc gamma receptor II (FcRII), which is important for understanding immune cell function.

Among these, one antibody (II8D2) specifically targets the FcRIIb isoform, allowing for detailed analysis of its distribution in immune cells, which was previously challenging due to a lack of suitable detection tools.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epitope mapping of new monoclonal antibodies recognizing distinct human FcRII (CD32) isoforms. Weinrich, V., Sondermann, P., Bewarder, N., et al.[2006]

Rituximab, a B cell-depleting monoclonal antibody, showed a 75% responsiveness rate in treating chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) based on a systematic review of 15 studies involving 96 patients.

The treatment resulted in significant improvements in disability scores and muscle power, particularly in patients who tested positive for anti-IgG4 antibodies, indicating its potential effectiveness in this specific subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of rituximab treatment in chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review and meta-analysis. Hu, J., Sun, C., Lu, J., et al.[2022]

The open-label phase 2 study (NCT04658472) will assess the efficacy and safety of SAR445088, a monoclonal antibody targeting complement C1s, in 90 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), focusing on different patient groups including those currently treated, refractory to treatment, and treatment-naïve.

The trial's innovative design utilizes Bayesian statistics to evaluate treatment responses and safety, aiming to provide a more efficient way to develop new therapies for CIDP, which currently has significant unmet treatment needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An innovative phase 2 proof-of-concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathy. Querol, L., Lewis, RA., Hartung, HP., et al.[2023]

Patients with chronic inflammatory demyelinating polyneuropathy (CIDP) show an imbalance in Fc-gamma receptor (FcγR) expression, with increased activating receptors and decreased inhibitory receptors compared to healthy individuals, indicating a disrupted immune response.

IV immunoglobulin (IVIg) therapy can partially restore the balance of FcγR expression on immune cells, suggesting that this treatment may help improve immune regulation in CIDP patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deregulated Fcγ receptor expression in patients with CIDP. Quast, I., Cueni, F., Nimmerjahn, F., et al.[2018]

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]

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]

The study identified two splice variants of the human high-affinity receptor for IgG (Fc gamma RI) through PCR-amplification cloning, which are important for understanding the receptor's function.

Both splice variants preserve the open reading frame, suggesting they may retain the ability to bind IgG, which is crucial for immune response mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variants of the human high-affinity receptor (Fc gamma RI) for immunoglobulin G. Chaikin, MA., Sweet, RW., Sylvester, DR., et al.[2019]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05327114

NCT05327114 | Efficacy and Safety Study of Nipocalimab ... The main purpose of this study is to evaluate the safety and efficacy of nipocalimab compared to placebo in delaying relapse in adults with chronic ...

2. clinicaltrialsregister.eu clinicaltrialsregister.eu/ctr-search/trial/2021-003234-37/IT

Clinical Trials Register ... Efficacy and Safety of Nipocalimab Administered to Adults with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). Studio di Fase 2/3 ...

3. jnj.com jnj.com/media-center/press-releases/nipocalimab-pivotal-phase-3-trial-demonstrates-longest-sustained-disease-control-in-fcrn-class

Nipocalimab pivotal Phase 3 trial demonstrates longest ... Patients treated with nipocalimab plus standard of care (SOC) achieved superiority over placebo plus SOC as measured by the primary endpoint of improvement in ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05327114/efficacy-and-safety-study-of-nipocalimab-for-adults-with-chronic-inflammatory-demyelinating-polyneuropathy-cidp

Efficacy and Safety Study of Nipocalimab for Adults With ... The main purpose of this study is to evaluate the safety and efficacy of nipocalimab compared to placebo in delaying relapse in adults with chronic ...

5. clinicaltrials.eu clinicaltrials.eu/inn/nipocalimab/

Nipocalimab – Application in Therapy and Current Clinical ... Study on the Effectiveness and Safety of Nipocalimab for Adults with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). Recruiting.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05327114

NCT05327114 | Efficacy and Safety Study of Nipocalimab ... The main purpose of this study is to evaluate the safety and efficacy of nipocalimab compared to placebo in delaying relapse in adults with chronic ...

7. innovativemedicine.jnj.com innovativemedicine.jnj.com/emea/newsroom/findings-from-pivotal-nipocalimab-phase-3-study-in-a-broad-antibody-positive-population-of-people-living-with-generalised-myasthenia-gravis-published-in-the-lancet-neurology

Findings from pivotal nipocalimab Phase 3 study in a broad ... Nipocalimab demonstrated a sustained reduction in autoantibody levels, one of the underlying causes of generalised myasthenia gravis (gMG), by up to 75% over a ...

8. io.nihr.ac.uk io.nihr.ac.uk/wp-content/uploads/2023/11/28008-Nipocalimab-for-Myasthenia-Gravis-V1.0-NOV2023-NON-CONF.pdf

Health Technology Briefing November 2023 Nipocalimab is currently in clinical development for the treatment of adults with generalised myasthenia gravis (gMG). gMG is a rare, long-term ...