NCT06290128进行中（未招募）3 期
A Phase 3, Double-blind, Placebo-controlled Study Evaluating Efficacy and Safety of Riliprubart in Participants With Refractory Chronic Inflammatory Demyelinating Polyneuropathy
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Sanofi
- 入组人数
- 109
- 试验地点
- 376
- 主要终点
- Percentage of participants experiencing a response
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Placebo Arm
Placebo Comparator
Placebo for 24 weeks followed by open-label extension phase with riliprubart for 24 weeks
干预措施: Placebo (Drug)
Riliprubart Arm
Experimental
Riliprubart for 24 weeks followed by open-label extension phase with riliprubart for 24 weeks
干预措施: Placebo (Drug)
Placebo Arm
Placebo Comparator
Placebo for 24 weeks followed by open-label extension phase with riliprubart for 24 weeks
干预措施: Riliprubart (Drug)
Riliprubart Arm
Experimental
Riliprubart for 24 weeks followed by open-label extension phase with riliprubart for 24 weeks
干预措施: Riliprubart (Drug)
结局指标
主要结局
Percentage of participants experiencing a response
时间窗: Baseline to week 24
A response is defined as a decrease of ≥1 point from baseline in adjusted INCAT disability score at Week 24.
Percentage of participants randomized to riliprubart with lasting response
时间窗: Baseline to week 48
Lasting response is defined as a decrease of ≥1 point in adjusted INCAT disability score at week 48 versus baseline.
Percentage of participants randomized to placebo who experience a response
时间窗: 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.
次要结局
- Number of participants with TEAEs, including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) for Part B(Week 24 to week 103)
- Incidence and titer of anti-riliprubart antibodies(Week 24 to week 103)
- Change from baseline in Inflammatory Raschbuilt Overall Disability Scale (IRODS) score(Baseline to week 24)
- Change from baseline in adjusted inflammatory neuropathy cause and treatment (INCAT) disability score(Baseline to week 24)
- Change from baseline in grip strength (kilopascals; dominant hand)(Baseline to week 48)
- Change from baseline in Medical Research Council Sum Score (MRC-SS)(Baseline to week 24)
- Incidence and titer of anti-riliprubart antibodies(Week 24 to week 111)
- Percentage of participants refractory to immunoglobulins experiencing a response(Baseline to week 24)
- Change from baseline in I RODS score(Baseline to week 48)
- Change from baseline in the EuroQol 5 Dimension, 5-Level Health Scale (EQ-5D-5L)(Baseline to week 24)
- Change from baseline in the Rasch-built modified fatigue severity scale (RT-FSS)(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(Baseline to week 24)
- Incidence and titer of anti-riliprubart antibodies (ADA)(Baseline to week 24)
- Number of participants with TEAEs, including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) for Part B(Week 24 to week 111)
- Change from baseline in adjusted INCAT score(Baseline to week 48)
- Change from baseline in MRC-SS(Baseline to week 48)
- Change from baseline in EQ-5D-5L score(Baseline to week 48)
- Change from baseline in RT-FSS(Baseline to week 48)
- Percentage of participants randomized to riliprubart who experience a response at Week 48 without prior response in Part A (delayed response)(Baseline to week 48)
- Change from baseline in grip strength (kilopascals; dominant hand)(Baseline to week 24)
研究者
研究点 (376)
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相关资讯
Sanofi Halts MOBILIZE Phase 3 Trial of Riliprubart in Refractory CIDP After Interim Analysis Shows Insufficient Efficacy- Sanofi announced the MOBILIZE phase 3 study of riliprubart in refractory CIDP will be stopped following an independent data monitoring committee interim analysis that found the trial unlikely to demonstrate sufficient efficacy.
- No safety signals related to riliprubart were identified during the interim analysis, and the company will evaluate continuation of the VITALIZE phase 3 study in IVIg-treated CIDP patients.
- Riliprubart is an IgG4 humanized monoclonal antibody targeting activated C1s in the classical complement pathway, designed to inhibit inflammatory mechanisms driving demyelination in CIDP.
- Approximately 30% of CIDP patients do not respond to standard therapies, and among responders roughly 70% have an incomplete response, underscoring the persistent unmet need in this rare neurological condition.3 months agoRiliprubart Shows Promise in CIDP Treatment with Significant Neurofilament Light Reduction- Phase 2 study results reveal that Sanofi's investigational riliprubart reduced plasma neurofilament light levels by 31% in patients with chronic inflammatory demyelinating polyneuropathy.
- Greater reductions in neurofilament light levels correlated with higher treatment response rates, with up to 69% of patients showing improvement in disability scores.
- Riliprubart, a selective inhibitor of the classical complement pathway, is now being evaluated in two global Phase 3 trials (MOBILIZE and VITALIZE) across 28 countries.last yearRiliprubart Shows Promise as First-in-Class Treatment for Chronic Inflammatory Demyelinating Polyneuropathy- Sanofi's riliprubart demonstrated significant disease-controlling benefits across all patient cohorts in a Phase 2 study for chronic inflammatory demyelinating polyneuropathy (CIDP), including those who failed standard treatments.
- The complement C1s inhibitor showed sustained efficacy for up to 48 weeks, with 87-92% of participants experiencing improvement or disease stabilization after 24 weeks of treatment.
- Riliprubart reduced neurofilament light chain levels by 35% across all cohorts, suggesting potential reduction in nerve damage, while also improving patient-reported fatigue and quality of life outcomes.2 years ago