Nipocalimab for CIDP
Recruiting in Palo Alto (17 mi)
+130 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Janssen Research & Development, LLC
Must be taking: Corticosteroids
Disqualifiers: Severe hepatic, Diabetes, Hypertension, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing nipocalimab, a medicine that helps the immune system, in adults with CIDP who initially respond to it. The goal is to see if it can safely and effectively delay the return of symptoms by blocking harmful immune actions.
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.
What data supports the effectiveness of the drug Nipocalimab for treating CIDP?
While there is no direct data on Nipocalimab for CIDP, similar treatments like Rituximab, which also target immune system components, have shown improvement in patients with CIDP, especially those with specific antibodies. This suggests that targeting immune pathways can be effective in managing CIDP symptoms.
12345What makes the drug Nipocalimab unique for treating CIDP?
Nipocalimab is unique because it targets the neonatal Fc receptor (FcRn), which is involved in recycling antibodies and prolonging their lifespan in the body. This mechanism is different from other treatments for CIDP, which typically focus on suppressing the immune system or reducing inflammation.
678910Eligibility Criteria
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.
+3 more
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.
+3 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: NipocalimabExperimental Treatment1 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: PlaceboPlacebo Group1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Advocate Health - Aurora St. Luke's Medical CenterMilwaukee, WI
Atrium HealthCharlotte, NC
Toronto General HospitalToronto, Canada
Augusta UniversityAugusta, GA
More Trial Locations
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Who Is Running the Clinical Trial?
Janssen Research & Development, LLCLead Sponsor
References
Efficacy of rituximab treatment in chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review and meta-analysis. [2022]Current standard treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) has been proved effective, but it is poorly effective in refractory patients and unclear for anti-IgG4 antibody-associated CIDP. Rituximab is a B cell-depleting monoclonal antibody. It has been applied as one of the management strategies in CIDP, but its efficacy is unknown.
Efficacy of low dose rituximab in treatment-resistant CIDP with antibodies against NF-155. [2020]We herein to describe the response and the potential treatment mechanism of low dose rituximab in patients with treatment-resistant chronic inflammatory demyelinating polyneuropathy (CIDP) with antibodies against neurofascin-155 (NF-155). Patients received 100 mg rituximab once weekly for 4 weeks followed by 100 mg per month for 2 additional doses. Clinical function scores, Fahn- Tolosa-Marin Tremor Rating Scale (FTMTRS) and flow cytometry of peripheral blood were scheduled before and at 1, 3, 6 months after rituximab treatment. All clinical function score including MRC, INCAT, Hughes, mRS, ODSS and FTMTRS scores showed obvious improvement at the post-treatment follow-up 1,3,6 months in comparison with baseline values. The proportion of CD19 + CD27+, CD19 + CD38+ and CD138 in lymphocytes of all patients declined at 1,3,6 month and the proportion of CD19 + CD24hiCD38hi in one patient was increased at 6 months after rituximab treatment. Low dose rituximab can significant improve disease severity and disabling tremor of CIDP patients with anti-NF155 antibody by the powerful role of B cell depletion within six months and subsequent reestablishment of B-cell subsets including increasing regulatory B cells, inhibiting memory B cells and reducing plasmablasts.
An innovative phase 2 proof-of-concept trial design to evaluate SAR445088, a monoclonal antibody targeting complement C1s in chronic inflammatory demyelinating polyneuropathy. [2023]Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare immune-mediated disease of the peripheral nerves, with significant unmet treatment needs. Clinical trials in CIDP are challenging; thus, new trial designs are needed. We present design of an open-label phase 2 study (NCT04658472) evaluating efficacy and safety of SAR445088, a monoclonal antibody targeting complement C1s, in CIDP.
Deregulated Fcγ receptor expression in patients with CIDP. [2018]To evaluate the expression of activating and inhibitory Fc-gamma receptors (FcγRs) before and during clinically effective therapy with IV immunoglobulin (IVIg) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP).
Autoantibodies to a Nodal Isoform of Neurofascin in Pediatric Chronic Inflammatory Demyelinating Polyneuropathy. [2023]Pediatric chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune-mediated disorder of the peripheral nervous system with a number of diagnostic pitfalls. A subset of treatment-resistant CIDP adult patients have been found with antibodies against paranodal proteins. We report the first pediatric case in a 14 year-old adolescent with a severe CIDP phenotype in whom positive anti-neurofascin 155 antibodies were found in his serum. Resistant to conventional therapies, he showed dramatic improvement when treated with Rituximab with mild to moderate functional motor disability at 24 month follow-up. In pediatric CIDP patients that remain refractory to conventional treatments, the presence of antibodies to paranodal proteins warrants investigation as it can have potential therapeutic guidance.
MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells. [2022]The neonatal Fc receptor (FcRn) for IgG, an MHC class I-related molecule, functions to transport IgG across polarized epithelial cells and protect IgG from degradation. However, little is known about whether FcRn is functionally expressed in immune cells. We show here that FcRn mRNA was identifiable in human monocytes, macrophages, and dendritic cells. FcRn heavy chain was detectable as a 45-kDa protein in monocytic U937 and THP-1 cells and in purified human intestinal macrophages, peripheral blood monocytes, and dendritic cells by Western blot analysis. FcRn colocalized in vivo with macrosialin (CD68) and Ncl-Macro, two macrophage markers, in the lamina propria of human small intestine. The heavy chain of FcRn was associated with the beta(2)-microglobulin (beta(2)m) light chain in U937 and THP-1 cells. FcRn bound human IgG at pH 6.0, but not at pH 7.5. This binding could be inhibited by human IgG Fc, but not Fab. FcRn could be detected on the cell surface of activated, but not resting, THP-1 cells. Furthermore, FcRn was uniformly present intracellularly in all blood monocytes and intestinal macrophages. FcRn was detectable on the cell surface of a significant fraction of monocytes at lower levels and on a small subset of tissue macrophages that expressed high levels of FcRn on the cell surface. These data show that FcRn is functionally expressed and its cellular distribution is regulated in monocytes, macrophages, and dendritic cells, suggesting that it may confer novel IgG binding functions upon these cell types relative to typical Fc gamma Rs: Fc gamma RI, Fc gamma RII, and Fc gamma RIII.
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]IgG antibodies have been used to treat many diseases including cancer. IgG antibody-drug conjugates (ADCs) deliver cytotoxic drugs to target cells for cell elimination, but they have dose limiting toxicity due to target-independent uptake, including pinocytotic uptake. Neonatal Fc receptor (FcRn) recycles pinocytosed IgG in a pH-dependent manner and is the receptor responsible for the long half-life of IgG. Use of IgG variants with stronger FcRn binding at pH 6.0 for ADCs might improve recycling efficiency and reduce toxicity. However, these variants have residual FcRn binding at pH 7.4, which could lead to FcRn-mediated uptake and higher toxicity. Thus, the uptake of such variants at pH 7.4 needs to be evaluated. Here we report a reproducible and quantitative assay using an inducible HM7 colorectal cancer cell line to measure IgG uptake at endogenous and overexpressed FcRn levels. Our assay had comparable reproducibility at pH 6.0, 6.8 and 7.4. The wild type (WT) IgG had similar uptake at endogenous and overexpressed FcRn levels, as expected for pinocytotic uptake. We found similar uptake of a WT IgG and a stronger FcRn binding T307Q/N434A variant (QA variant) at endogenous FcRn levels at pH 7.4, although the QA variant had higher uptake at overexpressed FcRn levels. The QA variant also had higher uptake than the WT IgG at overexpressed FcRn levels at pH 6.8. Our assay can be used to characterize the stronger FcRn binding variants to aid in selection of suitable variants with low uptake at pH 7.4 for use as ADCs.
Variants of the human high-affinity receptor (Fc gamma RI) for immunoglobulin G. [2019]PCR-amplification cloning of the cDNA encoding the human high-affinity receptor for IgG (Fc gamma RI) revealed two splice variants which coincide with domain boundaries predicted by amino acid sequence comparison. Both splice variants maintain the open reading frame.
Epitope mapping of new monoclonal antibodies recognizing distinct human FcRII (CD32) isoforms. [2006]The class II Fc gamma receptors are widely distributed on cells of the immune system. Nevertheless, the exact cell type distribution of the FcRII isoforms is still unclear because of the lack of appropriate antibodies that discriminate between the various isoforms. In this study we describe the generation and characterization of three monoclonal antibodies (MAbs) raised against recombinant human FcRIIb2 as well as a synthetic peptide (amino acids 30-39) of this receptor. Analyses of the isoform specificity of these antibodies using ELISA and Western blots revealed that the MAbs II1A5 (mIgG1) and ID2.7 (mIgM) are pan FcRII antibodies recognizing all known FcRII isoforms. In contrast, the MAb II8D2 (mIgG1) specifically reacts with FcRIIb but not with FcRIIa. The observed antibody reactivities could be confirmed by examination of the exact epitopes using overlapping 15-mer peptides spanning the entire FcRIIb2. So far these antibodies are the only ones described that detect FcRII in Western blots. Moreover, they can be used to analyze the cellular FcRII isoform distribution at the protein level, which was otherwise not possible.
FcγRIIB as a key determinant of agonistic antibody efficacy. [2016]Fc gamma Receptor (FcγR) IIB (CD32B) is an immunoreceptor tyrosine inhibitory motif (ITIM)-bearing Fc receptor that is involved in abrogating the signalling and function delivered from other receptors; archetypally those arising from other, activatory, FcγR and from the B cell receptor (BCR) for antigen. In the context of immunotherapy, it has convincingly been shown to limit a variety of clinically important therapeutic monoclonal antibodies (mAb) such as rituximab and trastuzumab in preclinical models. However, recent exploration of so-called immunomodulatory mAb, for example agonist mAb directed against various members of the TNFR super-family, has cast new light on the ability of FcγRIIB to regulate immune responses and immunotherapy. These data, accumulated by several independent groups, have shown the seemingly paradoxical ability of FcγRIIB to augment or even be absolutely required for the activity of this class of mAb. In this review we highlight the key role of FcγRIIB in regulating agonistic mAb, detail the likely mechanism of action and propose new ways in which this information may be exploited therapeutically.