chronic inflammatory demyelinating polyneuropathy
Conditions
Interventions
Drug: Riliprubart (SAR445088)
Pharmaceutical form: Solution, Route of administration: intravenous (IV) Infusion
Drug: Placebo
Pharmaceutical form: Solution, Route of administration: IV Infusion
Drug
Sponsors
Obara Kentaro
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: - Participant must have chronic inflammatory demyelinating polyneuropathy (CIDP) or possible CIDP criteria, based on European Academy of Neurology (EAN)/ Peripheral Nerve Society (PNS) Task Force CIDP guidelines, second revision (2021) - Participant must have either typical CIDP, or one of the following two CIDP variants: motor CIDP (including motor predominant), multifocal CIDP (also known as Lewis Sumner Syndrome). Diagnosis must be confirmed by the adjudication committee - Participant must be refractory to either immunoglobulin therapy or corticosteroid therapy, as defined below - - Immunoglobulin-refractory subgroup: Historic evidence of failure or inadequate response to immunoglobulin therapy prior to screening, defined as no clinically meaningful improvement or persistent inflammatory neuropathy cause and treatment (INCAT) score >=2 after a minimum of: - - - One dose of intravenous immunoglobulin (IVIg) of 2 g/kg, followed by either a second dose of 2 g/kg or at least 2 doses of 1 g/kg, with a separation of approximately 3 weeks between doses (each dose can be divided over 2 to 5 days), as indicated in the EAN/PNS 2021 guidelines OR - - - Subcutaneous immunoglobulin (SCIg) maintenance therapy with at least 0.2 g/kg weekly for 5 weeks - - Corticosteroid-refractory subgroup: Historic evidence of failure or inadequate response to corticosteroid therapy prior to screening, defined as no clinically meaningful improvement or persistent INCAT score >=2 after a minimum of 12 weeks of corticosteroid therapy. Corticosteroid regimen can be daily oral prednisone/prednisolone, at least 60 mg, equivalent to methylprednisolone 48 mg, tapered over 6 to 8 months, or alternative regimens, e.g. pulsed high-dose corticosteroid treatment (40 mg/day oral dexamethasone or 500 mg/day intravenous (IV) methylprednisolone, each daily for 4 days per month for 6 months), as indicated in the EAN/PNS 2021 guidelines. A clinically meaningful improvement is defined as one or more of the following: - - - A >=1 point decrease in adjusted INCAT disability score - - - An increase in Inflammatory rasch-built overall disability scale (I-RODS) centile score >=4 points - - - An increase in Medical Research Council (MRC) Sum score >=3 points - - - An improvement in hand grip strength of >=8 kilopascals or - - - Equivalent improvement based on information from medical records and per the Investigator's judgment - Participant has an INCAT score of 2 to 9 (a score of 2 should be exclusively from the leg disability component of INCAT) - Any allowed immunosuppressant drugs (azathioprine, cyclosporine, or mycophenolate mofetil) have been taken for >=6 months at a stable dose for >=3 months prior to Screening - Participant may be receiving low-dose oral corticosteroids (==3 months prior to Screening - Participant must have active disease, defined by a CIDP disease activity score (CDAS) of >=2 points at Screening - Participant must have documented vaccinations against encapsulated bacterial pathogens given within 5 years prior to Day 1 or initiated a minimum of 14 days prior to first dose of study intervention - All participants must agree to use contraception methods during and after the study as required - Contraceptive use by men and women participating
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: - Polyneuropathy of other causes, including but not limited to: acute demyelinating polyneuropathies (eg, Guillain-Barre syndrome), hereditary demyelinating neuropathies, neuropathies secondary to infection or systemic disease, diabetic neuropathy, drug- or toxin-induced neuropathies, multifocal motor neuropathy, polyneuropathy related to immunoglobulin M (IgM) monoclonal gammopathy, polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome, and lumbosacral radiculoplexus neuropathy - Sensory CIDP, Distal CIDP and focal CIDP variants. - Any other neurological or systemic disease that can cause symptoms and signs interfering with treatment or outcome assessments - Poorly controlled diabetes (hemoglobin A1c [HbA1c] >7% at the Screening visit) - Serious infections requiring hospitalization within 30 days prior to Screening and any active infection requiring treatment during screening or presence of a condition that may predispose the participant to increased risk of infection (eg, medical history such as known immunodeficiency or history of recurrent infections) - Clinical diagnosis of Systemic Lupus Erythematosus (SLE) or family history of SLE. For a participant with an antinuclear antibody (ANA) titer >= 1:160 and a positive anti- double-stranded DNA (anti-dsDNA) at Screening, SLE diagnosis must be ruled out prior to enrollment - Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study. Specifically, history of any hypersensitivity reaction to riliprubart or its components or of a severe allergic or anaphylactic reaction to any humanized or murine monoclonal antibody - Any other clinically meaningful medical history or ongoing medical condition (as determined by the Investigator at Screening) that might impact benefit-risk assessment, jeopardize the safety of the participant, or compromise the quality of the data collected in this study; or history or presence of other significant concomitant illness that would adversely affect participation in this study, per Investigator's judgment - Documented history of attempted suicide over the 6 months prior to the Screening visit, presence of suicidal ideation of category 4 or 5 on Columbia Suicide Severity Rating Scale (C-SSRS) during screening, OR if in the Investigator's judgment, the participant is at risk for a suicide attempt - Evidence of CIDP worsening within the 6 weeks following a prior vaccination that, in the opinion of the Investigator, constituted a relapse - Recent or planned major surgery that could confound the results of the trial or put the participant at undue risk - Participant has received immunoglobulins (IVIg or SCIg) within 12 weeks prior to Screening - Treatment with plasma exchange within the 8 weeks prior to Screening - Prior treatment with riliprubart - Prior treatment with (any time) with highly immunosuppressive/chemotherapeutic medications with sustained effects, eg, mitoxantrone, alemtuzumab, cladribine - Prior treatment (any time) with total lymphoid irradiation or bone marrow transplantation - Prior treatment with B-cell-depleting agents such as rituximab within 6 months prior to riliprubart dosing, or until return of B-cell counts to normal levels, whichever is longer - Use of any specific complement system inhibitor (eg, eculiz
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Percentage of participants experiencing a response [Time Frame: Baseline to Week 24] A response is defined as a decrease of >=1 point from baseline in adjusted inflammatory neuropathy cause and treatment (INCAT) disability score at Week 24. 2. Percentage of participants randomized to riliprubart with lasting response [Time Frame: Baseline to Week 48] Lasting response is defined as a decrease of >= 1 point in adjusted INCAT disability score at week 48 versus baseline. 3. Percentage of participants randomized to placebo who experience a response [Time Frame: Week 24 to Week 48] A response is defined as a decrease of >=1 point in adjusted INCAT disability score at Week 48 versus week 24. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Change from baseline in Inflammatory Rasch-built Overall Disability Scale (I-RODS) score [Time Frame: Baseline to Week 24] 2. Change from baseline in adjusted INCAT disability score [Time Frame: Baseline to Week 24] 3. Change from baseline in grip strength (kilopascals; dominant hand) [Time Frame: Baseline to Week 24] 4. Change from baseline in Medical Research Council Sum Score (MRC-SS) [Time Frame: Baseline to Week 24] 5. Percentage of participants refractory to immunoglobulins experiencing a response [Time Frame: Baseline to Week 24] A response is defined as a decrease of >=1 point from baseline in adjusted INCAT disability score at Week 24 6. Change from baseline in the EuroQol 5 Dimension, 5-Level Health Scale (EQ-5D-5L) [Time Frame: Baseline to Week 24] 7. Change from baseline in the Rasch-built modified fatigue severity scale (RT-FSS) [Time Frame: Baseline to Week 24] 8. Number of participants with treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) and adverse events of special interest (AESIs) for Part A [Time Frame: Baseline to Week 24] 9. Incidence and titer of anti-riliprubart antibodies (ADA) [Time Frame: Baseline to Week 24] 10. Number of participants with TEAEs, including SAEs and AESIs for Part B [Time Frame: Week 24 to Week 111] 11. Incidence and titer of ADA [Time Frame: Week 24 to Week 111] 12. Change from baseline in I-RODS score [Time Frame: Baseline to Week 48] 13. Change from baseline in adjusted INCAT disability score [Time Frame: Baseline to Week 48] 14. Change from baseline in grip strength (kilopascals; dominant hand) [Time Frame: Baseline to Week 48] 15. Change from baseline in MRC-SS [Time Frame: Baseline to Week 48] 16. Percentage of participants randomized to riliprubart who experience a response at Week 48 without prior response in Part A (delayed response) [Time Frame: Baseline to week 48] A delayed response is defined as a decrease of >=1 point in adjusted INCAT disability score at Week 48 versus ba | — |
Countries
Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czechia, Denmark, France, Germany, Greece, Italy, Japan, Mexico, Netherlands, Poland, Portugal, Republic of Korea, Spain, Sweden, Taiwan, Turkey, United States
Contacts
Public ContactUnit Clinical
Sanofi K.K.
Outcome results
None listed