We thank the Japan Agency for Medical Research and Development for its financial support of this research (grant number JP19lk0201080), which is covering almost all the operational costs of this trial

We thank the Japan Agency for Medical Research and Development for its financial support of this research (grant number JP19lk0201080), which is covering almost all the operational costs of this trial. Abbreviations CASPR 1contactin-associated protein 1.CIDPchronic inflammatory demyelinating polyradiculoneuropathy.CNTN1contactin-1.EFNS/PNSEuropean Federation of TCS2314 Neurological Societies/Peripheral Nerve Society.Igimmunoglobulin.INCATInflammatory Neuropathy Cause and Treatment.IVIgintravenous immunoglobulin.MuSKmuscle-specific tyrosine kinase.NF155neurofascin-155.PMDAPharmaceuticals and Medical Device Agency. Footnotes Conflicts of Interest: None declared.. functional outcome assessed using the adjusted Inflammatory Neuropathy Cause and Treatment Disability Scale score at 26, 38, or 52 weeks after the start of treatment with rituximab in patients with CIDP and anti-paranodal protein antibodies. Secondary outcome measures include grip strength, manual muscle testing sum scores, results of nerve conduction studies, Rabbit Polyclonal to RGAG1 and other functional scales. Results We plan to enroll 25 cases for the full analysis set. Recruitment is ongoing, with 14 patients enrolled as of January 2020. Enrollment will close in September 2020, and the study is planned to end in December 2021. Conclusions This randomized controlled trial will determine if rituximab is safe and effective in patients with anti-paranodal antibodies. An open-label study will provide additional data on the effects of rituximab in patients with antibody-negative CIDP. The results of the RECIPE trial are expected to provide evidence for the positioning of rituximab as a pathogenesis-based therapeutic for refractory CIDP. Trial Registration ClinicalTrials.gov “type”:”clinical-trial”,”attrs”:”text”:”NCT03864185″,”term_id”:”NCT03864185″NCT03864185, https://clinicaltrials.gov/ct2/show/”type”:”clinical-trial”,”attrs”:”text”:”NCT03864185″,”term_id”:”NCT03864185″NCT03864185 ; The Japan Registry of Clinical Trials jRCT2041180037, https://jrct.niph.go.jp/en-latest-detail/jRCT2041180037 International Registered Report Identifier (IRRID) DERR1-10.2196/17117 values 0.05 will be considered statistically significant. Monitoring and Auditing Monitoring and auditing will include systematic independent examination according to the study protocol, applicable regulatory requirements, and standard operating procedures. Results Ethics Approval, Trial Registration, and Current Enrollment Status The study protocol complies with the Declaration of Helsinki [38] and the Pharmaceutical Affairs Act in Japan. This protocol was also approved by the institutional review boards at the following sites: Nagoya University Hospital (No. 302010), Chiba University Hospital (No. 030033), Yamaguchi University Hospital (No. 201901), and Kyushu University Hospital (No. 2018312). The necessary information for the RECIPE trial has been uploaded to ClinicalTrials.gov (“type”:”clinical-trial”,”attrs”:”text”:”NCT03864185″,”term_id”:”NCT03864185″NCT03864185, registered March 6, 2019) and the Japan Registry of Clinical Trials (jRC2041180037, registered January 31, 2019). The first patient completed registration in April 2019 and received an TCS2314 investigational treatment in May 2019. Recruitment of patients for the RECIPE trial is ongoing at the four participating hospitals. As of January 2020, 14 cases have been enrolled. The targeted accrual is 25 cases for the full analysis set. Enrollment will close in September 2020, and the study is scheduled to end in December 2021. Discussion Overview There have been some reports on the epidemiology of IgG4 antibodyCpositive CIDP [14,16,17]. This phenotypic subtype presents as subacute or slowly progressive disease. The initial disability tends to be distal acquired demyelinating symmetric neuropathy, which sometimes progresses to the typical CIDP phenotype. IgG4 antibodyCpositive CIDP is also characterized by gait disturbance with sensory ataxia and fine tremor of the hands. The protein level in cerebrospinal fluid is markedly higher in IgG4 antibodyCpositive CIDP than in typical CIDP. Furthermore, a relatively large proportion of patients with antibodyCpositive CIDP present at a younger age. However, they are resistant to conventional therapies, such as IVIg and corticosteroids. Therefore, new therapies that can inhibit production of pathogenic antibodies in the long term are essential. Rituximab can be expected to be effective in cases of refractory CIDP [19-32]. Some of the phenotypic characteristics, for example onset time, are different from those in anti-CNTN1Cpositive patients and anti-NF155 patients; however, patients with IgG4 autoantibodyCpositive CIDP have several clinically common characteristics. Given its mechanism of action, rituximab is likely to be effective in patients with IgG4 autoantibody (anti-CNTN1 and anti-NF155)Cpositive CIDP. Accordingly, we are planning to develop TCS2314 rituximab for use in these.