A Study to Test the Effects and Safety of Riliprubart in People With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) for Which the Usual Treatments do Not Work

Официальное название

A Phase 3, Double-blind, Placebo-controlled Study Evaluating Efficacy and Safety of Riliprubart in Participants With Refractory Chronic Inflammatory Demyelinating Polyneuropathy

Обзор

The purpose of the study is to evaluate efficacy of riliprubart compared to placebo in adult participants with CIDP whose disease is refractory to standard of care. The study duration will be for a maximum of 111 weeks including screening, treatment phases, and follow-up.

Вмешательства

• Препарат Riliprubart
  Pharmaceutical form: Solution Route of administration: IV Infusion
• Препарат Placebo
  Pharmaceutical form: Solution Route of administration: IV Infusion
• Препарат Riliprubart
  Pharmaceutical form: Solution Route of administration: SC Injection
• Препарат Placebo
  Pharmaceutical form: Solution Route of administration: SC Injection

Первичные конечные точки

• Percentage of participants experiencing a response [Срок оценки: Baseline to week 24]
• Percentage of participants randomized to riliprubart with lasting response [Срок оценки: Baseline to week 48]
• Percentage of participants randomized to placebo who experience a response [Срок оценки: Week 24 to week 48]

Вторичные конечные точки (12)

• Change from baseline in Inflammatory Raschbuilt Overall Disability Scale (IRODS) score [Срок оценки: Baseline to week 24]
• Change from baseline in adjusted inflammatory neuropathy cause and treatment (INCAT) disability score [Срок оценки: Baseline to week 24]
• Change from baseline in grip strength (kilopascals; dominant hand) [Срок оценки: Baseline to week 24]
• Change from baseline in Medical Research Council Sum Score (MRC-SS) [Срок оценки: Baseline to week 24]
• Percentage of participants refractory to immunoglobulins experiencing a response [Срок оценки: Baseline to week 24]
• Change from baseline in the EuroQol 5 Dimension, 5-Level Health Scale (EQ-5D-5L) [Срок оценки: Baseline to week 24]
• Change from baseline in the Rasch-built modified fatigue severity scale (RT-FSS) [Срок оценки: Baseline to week 24]
• Number of participants with treatment emergent adverse events (TEAEs), including serious adverse events (SAEs) and adverse events of special interest (AESIs) for Part A [Срок оценки: Baseline to week 24]
• Incidence and titer of anti-riliprubart antibodies (ADA) [Срок оценки: Baseline to week 24]
• Number of participants with TEAEs, including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) for Part B [Срок оценки: Week 24 to week 103]
• Incidence and titer of anti-riliprubart antibodies [Срок оценки: Week 24 to week 103]
• Change from baseline in I RODS score [Срок оценки: Baseline to week 48]

Критерии участия

Критерии включения

Participants are eligible to be included in the study only if all of the following criteria apply:

• Participant must have 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, 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
• Corticosteroid-refractory subgroup: Historic evidence of failure or inadequate response to corticosteroid therapy prior to screening
• Participant has an INCAT score of 2 to 9
• Any allowed immunosuppressant drugs (azathioprine, cyclosporine, or mycophenolate mofetil) have been taken for ≥6 months
• Participant may be receiving low-dose oral corticosteroids (≤20 mg/day of prednisone or equivalent)
• 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
• Contraception for sexually active male or female participants; not pregnant or breastfeeding; no sperm donating for male participant
• A body weight at Screening of 35 kg to 154 kg (77 to 340 lbs), inclusive

Критерии исключения

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-Barré 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, 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
• Serious infections requiring hospitalization within 30 days prior to Screening and any active infection requiring antimicrobial 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 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 recently received immunoglobulins (IVIg or SCIg)
• Recent treatment with plasma exchange
• 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
• Use of any specific complement system inhibitor (eg, eculizumab) within 12 weeks or 5 times the half-life of the product, whichever is longer
• Treatment within 6 months prior to dosing with immunosuppressive/ chemotherapeutic medications, such as cyclophosphamide, methotrexate, tacrolimus, interferon, or tumor necrosis factor (TNF)-α inhibitors. Certain immunosuppressants commonly used in CIDP (azathioprine, cyclosporine, or mycophenolate mofetil) are allowed, as indicated under inclusion criterion.
• Any vaccination received within 28 days prior to dosing (with few exceptions to be confirmed at screening)
• Participation in another clinical trial with an investigational drug or receipt of an investigational product within 12 weeks or 5 times the half-life of the product, whichever is longer, prior to Screening
• Any screening laboratory values outside normal limits or abnormal ECG considered in the Investigator's judgment to be clinically significant in the context of this trial
• Positive result of any of the following tests:

• Hepatitis B surface antigen (HBsAg).
• Anti-hepatitis B core antibodies (anti-HBc Ab) (unless anti-hepatitis B surface antibodies \[anti-HBs Ab\] are also positive, indicating natural immunity).
• Anti-hepatitis C virus (anti-HCV) antibodies (participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis RNA test is obtained).
• Anti-human immunodeficiency virus 1 and 2 (anti-HIV1 and anti-HIV2) antibodies.
• Pregnancy, defined as a positive result of a highly sensitive urine or serum pregnancy test, or lactation
• Accommodation in an institution because of regulatory or legal order; eg, imprisoned or legally institutionalized
• Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or potential risk for noncompliance to study procedures
• Participants are employees at the clinical study site or other individuals directly involved in the conduct of the study, or immediate family member of such individuals
• Any country related specific regulation that would prevent the participant from entering the study
• Recent treatment with efgartigimod

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 28 центров

• Alabama Neurology Associates- Site Number : 8400019 — Homewood
• USC Norris Comprehensive Cancer Center- Site Number : 8400002 — Los Angeles
• University of California Irvine - Manchester Pavilion- Site Number : 8400007 — Orange
• IMMUNOe International Research Centers - Centennial- Site Number : 8400049 — Centennial
• Yale University School of Medicine- Site Number : 8400018 — New Haven
• Nova Clinical Research - Bradenton- Site Number : 8400044 — Bradenton
• Design Neuroscience Center- Site Number : 8400053 — Miami Lakes
• NorthShore University Health System - Glenbrook Hospital- Site Number : 8400024 — Glenview
• … и ещё 20 центров

Китай · 16 центров

• Investigational Site Number : 1560013 — Пекин
• Investigational Site Number : 1560010 — Пекин
• Investigational Site Number : 1560005 — Пекин
• Investigational Site Number : 1560016 — Пекин
• Investigational Site Number : 1560009 — Чанша
• Investigational Site Number : 1560011 — Чэнду
• Investigational Site Number : 1560002 — Фучжоу
• Investigational Site Number : 1560012 — Гуанчжоу
• … и ещё 8 центров

Испания · 10 центров

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Япония · 9 центров

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Италия · 8 центров

• Investigational Site Number : 3800001 — Milan
• … и ещё 7 центров

Бразилия · 6 центров

• Centro de Diagnostico e Pesquisa da Osteoporose do Espirito Santo- Site Number : 0760012 — Vitória
• Hospital Sao Rafael- Site Number : 0760011 — Salvador
• Freire Pesquisa Clínica - Belo Horizonte - Rua Piauí- Site Number : 0760016 — Belo Horizonte
• Hospital Moinhos de Vento- Site Number : 0760003 — Porto Alegre
• Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto- Site Number : 0760007 — Ribeirão Preto
• PSEG Centro de Pesquisa Clínica- Site Number : 0760009 — São Paulo

Германия · 6 центров

• Investigational Site Number : 2760001 — Bad Homburg
• Investigational Site Number : 2760004 — Berlin
• Investigational Site Number : 2760007 — Bochum
• Investigational Site Number : 2760005 — Essen
• Investigational Site Number : 2760003 — Giessen
• Investigational Site Number : 2760006 — Tübingen

Turkey (Türkiye) · 6 центров

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Франция · 5 центров

• Investigational Site Number : 2500001 — Le Kremlin-Bicêtre
• Investigational Site Number : 2500003 — Lille
• Investigational Site Number : 2500002 — Marseille
• Investigational Site Number : 2500005 — Montpellier
• Investigational Site Number : 2500004 — Paris

Португалия · 4 центра

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Аргентина · 3 центра

• Investigational Site Number : 0320001 — Buenos Aires
• Investigational Site Number : 0320002 — Buenos Aires
• Investigational Site Number : 0320003 — Buenos Aires

Чили · 3 центра

• Investigational Site Number : 1520003 — Lo Barnechea
• Investigational Site Number : 1520002 — Santiago
• Investigational Site Number : 1520001 — Santiago

Чехия · 3 центра

• Investigational Site Number : 2030004 — Brno
• Investigational Site Number : 2030003 — Hradec Králové
• Investigational Site Number : 2030002 — Pardubice

Греция · 3 центра

• Investigational Site Number : 3000002 — Athens
• Investigational Site Number : 3000003 — Larissa
• Investigational Site Number : 3000001 — Thessaloniki

Мексика · 3 центра

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Польша · 3 центра

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South Korea · 3 центра

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Тайвань · 3 центра

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Болгария · 2 центра

• Investigational Site Number : 1000002 — Blagoevgrad
• Investigational Site Number : 1000001 — Pleven

Дания · 2 центра

• Investigational Site Number : 2080002 — Aarhus
• Investigational Site Number : 2080001 — Copenhagen

Нидерланды · 2 центра

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Бельгия · 1 центр

• Investigational Site Number : 0560001 — Leuven

Канада · 1 центр

• Investigational Site Number : 1240001 — Québec

Швеция · 1 центр

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Идентификаторы

NCT: NCT06290128 · EFC17236 · U1111-1295-5755 · 2023-506503-26

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗