NCT06290141招募中3 期
A Phase 3, Randomized, Double-blind, Study Evaluating Efficacy and Safety of Riliprubart Versus Intravenous Immunoglobulin (IVIg) in Participants With 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
- 招募中
- 发起方
- Sanofi
- 入组人数
- 160
- 试验地点
- 236
- 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 IVIg in adult participants with CIDP who are receiving maintenance treatment with IVIg. The study duration will be for a maximum of 109 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 2 CIDP variants: motor CIDP, multifocal CIDP (also known as Lewis Sumner Syndrome). Diagnosis must be confirmed by the study adjudication committee.
- •Participants must have responded to IVIg in the past 5 years.
- •Participant must be on a stable maintenance dosage of IVIg.
- •Participant must have residual disability, defined as an INCAT score of 2 to 9 at Screening that is confirmed at baseline (a score of 2 should be exclusively from leg disability component of INCAT).
- •Participant must be receiving treatment with IVIg within a standard maintenance dosing regimen, defined as per EAN/PNS 2021 CIDP guidelines.
- •Participants receiving IVIg infusions at home are eligible, as long as IVIg infusions are switched to a hospital or infusion center setting at least 1 cycle prior to baseline.
- •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
- •Participant must have a body weight at Screening of 35 kg to 154 kg (77 to 340 lbs) inclusive.
- •Evidence of at least one clinically meaningful deterioration within 2 years, or at least 2 clinically meaningful deteriorations within 5 years prior to screening which occurred during period of interrupted dosing, reduced dosage, or extended intervals between doses of immunoglobin therapy, as verified by clinical examination or medical records.
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 IgM monoclonal gammopathy, POEMS syndrome, 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, 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 contraindication related to the administration of immunoglobulins (eg hypersensitivity, chronic kidney disease, thromboembolic diseases or recent thromboembolic event, known history of IgA deficiency at the time of Screening).
- •Any other clinically meaningful medical history or ongoing medical condition (as determined by the Investigator at Screening) that might impact the 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 the 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 the 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.
- •Recent treatment with plasma exchange
- •Treatment within 3 months prior to dosing with immunosuppressive/ immunomodulator medication, or corticosteroids (with exception of maintenance dose, which is allowed), or prior treatment (at any time) with highly immunosuppressive/ chemotherapeutic medications with sustained effects (eg, mitoxantrone, alemtuzumab, or cladribine).
- •Prior treatment with riliprubart.
- •Recent use of any specific complement system inhibitor (eg, eculizumab).
- •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.
- •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; imprisoned or legally institutionalized.
- •Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.
- •Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals.
- •Any country-related specific regulation that would prevent the participant from entering the study as defined by the protocol.
- •Recent treatment with efgartigimod.
- •The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
研究组 & 干预措施
Riliprubart Arm
Experimental
Riliprubart + Placebo IVIg for 24 weeks followed by open-label extension phase with riliprubart for 24 weeks
干预措施: riliprubart (Drug)
IVIg Arm
Active Comparator
IVIg (IVIg continuation) + Placebo riliprubart for 24 weeks followed by open-label extension phase with riliprubart for 24 weeks
干预措施: riliprubart (Drug)
IVIg Arm
Active Comparator
IVIg (IVIg continuation) + Placebo riliprubart for 24 weeks followed by open-label extension phase with riliprubart for 24 weeks
干预措施: IVIg (Drug)
Riliprubart Arm
Experimental
Riliprubart + Placebo IVIg for 24 weeks followed by open-label extension phase with riliprubart for 24 weeks
干预措施: Placebo (Drug)
IVIg Arm
Active Comparator
IVIg (IVIg continuation) + Placebo riliprubart for 24 weeks followed by open-label extension phase with riliprubart for 24 weeks
干预措施: Placebo (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 decrease of ≥1 point from baseline in adjusted INCAT disability score at Week 24
Percentage of participants randomized to riliprubart who responded during part A and had a lasting response during the open-label treatment extension period
时间窗: Baseline to week 48
Lasting response is defined as a decrease of ≥1 point in adjusted INCAT disability score
次要结局
- Change from baseline in Rasch-built Overall Disability Scale (I-RODS) 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 24)
- Change from baseline in Medical Research Council Sum Score (MRC-SS)(Baseline to week 24)
- Change from baseline in the Rasch-built modified fatigue severity scale (RT-FSS)(Baseline to week 24)
- Percentage of participants experiencing a relapse(Baseline to week 24)
- Change from baseline in the EuroQol 5 Dimension, 5-Level Health Scale (EQ-5D-5L)(Baseline to week 24)
- Number of participants with TEAEs, including SAEs and AESIs for Part A(Baseline to week 24)
- Number of participants with treatment-emergent ADA in participants treated with riliprubart(Baseline to week 24)
- Number of participants with TEAEs, including SAEs and AESIs(Week 24 to week 48)
- Incidence and titer of anti-drug antibodies (ADA) during open-label treatment and follow-up(Baseline to week 109)
- Change from baseline in I-RODS(Baseline to week 48)
- Change from baseline in adjusted INCAT score(Baseline to week 48)
- Change from baseline in grip strength (kilopascals; dominant hand)(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)
- Percentage of participants randomized to IVIg continuation who experienced a response(Week 24 to week 48)
- Percentage of participants randomized to riliprubart who experienced a response at Week 48 without prior response in Part A (delayed response)(Baseline to Week 48)
- Percentage of participants randomized to riliprubart experiencing a relapse(Week 24 to week 48)
- Change from baseline in RT-FSS(Baseline to week 48)
- Percentage of participants randomized to IVIg continuation experiencing a relapse(Week 24 to week 48)
- Percentage of participants randomized to riliprubart experiencing a relapse(Baseline to week 48)
研究者
研究点 (236)
Loading locations...
相似试验
进行中（未招募）
3 期
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 WorkChronic Inflammatory Demyelinating PolyradiculoneuropathyPolyneuropathy, Inflammatory Demyelinating, ChronicNCT06290128Sanofi109
已完成
3 期
Safety and Efficacy of E/C/F/TDF Versus RTV-Boosted ATV Plus FTC/TDF in HIV-1 Infected, Antiretroviral Treatment-Naive WomenAcquired Immunodeficiency SyndromeHIV InfectionsNCT01705574Gilead Sciences583
已完成
3 期
Study of PROVIGIL ® (Modafinil) Treatment in Children and Adolescents With Excessive Sleepiness Associated With Obstructive Sleep Apnea/Hypopnea SyndromeSleep Apnea, ObstructiveNCT00107809Cephalon140
进行中（未招募）
3 期
Ibrutinib Before and After Stem Cell Transplant in Treating Patients With Relapsed or Refractory Diffuse Large B-cell LymphomaRecurrent Diffuse Large B-Cell Lymphoma Activated B-Cell TypeRefractory Diffuse Large B-Cell Lymphoma Activated B-Cell TypeNCT02443077National Cancer Institute (NCI)94
已完成
3 期
Study to Evaluate the Safety and Efficacy of E/C/F/TAF (Genvoya®) Versus E/C/F/TDF (Stribild®) in HIV-1 Positive, Antiretroviral Treatment-Naive AdultsHIVHIV InfectionsNCT01780506Gilead Sciences872
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