2023-508338-33-00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
Sanofi-Aventis Recherche & Developpement33 个研究点 分布在 9 个国家目标入组 87 人开始时间: 2024年7月15日最近更新:
适应症
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 87
- 试验地点
- 33
- 主要终点
- Percentage of participants experiencing a response
研究概览
简要总结
- To evaluate the efficacy of riliprubart relative to IVIg continuation as measured by the INCAT disability scale
- To evaluate long-term efficacy of riliprubart as measured by the INCAT disability scale
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Participant must have CIDP or possible CIDP criteria, based on European Academy of Neurology (EAN)/ Peripherial Nerve Society (PNS) Task Force CIDP guidelines, second revision (2021).
- •Participant must be receiving treatment with IVIg within a standard maintenance dosing regimen, defined as per EAN/PNS 2021 CIDP guidelines: 0.4 to 1 g/kg every 2 to 6 weeks.The IVIg maintenance dosing regimen should be equivalent or higher than a weekly dose of 0.1 g/kg body weight (for example, 0.3 g/kg every 3 weeks).
- •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.
- •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.
- •All participants must agree to use contraception methods during and after the study as required.
- •Contraceptive use by men and women participating in the study should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •A male participant is eligible to participate if they agree to the following during the study intervention period and for at least 55 weeks after the last dose of study medication. --Refrain from donating or cryopreserving sperm. PLUS, either: --Be abstinent from heterosexual intercourse (abstinent on a long-term and persistent basis) and agree to remain abstinent. OR --Must agree to use contraception/barrier as detailed below: -A male condom and an additional highly effective contraceptive method (Contraceptive and barrier guidance per protocol) when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant.
- •A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: --Is a woman of nonchildbearing potential (WONCBP) as defined by the protocol. OR --Is a WOCBP and agrees to use a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, as described in the protocol during the study intervention period (to be effective before starting the intervention) and for at least 55 weeks after the last administration of study intervention and agrees not to donate or cryopreserve eggs (ova, oocytes) for the purpose of reproduction during this period.
- •Participant must have either typical CIDP, or one of the following 2 CIDP variants: motor CIDP (including motor-predominant 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. Response must be an objective clinically meaningful improvement defined by at least one of the following: ≥1 point decrease in adjusted INCAT score, ≥4 points increase in I-RODS centile score, ≥3 points increase in the MRC-SS, ≥8 kilopascal improvement in mean grip strength (1 hand), or an equivalent improvement based on information documented in medical records as per the Investigator’s judgment.
- •Participant must be on a stable maintenance dosage of IVIg, defined as no change greater than 10% in frequency or dose of IVIg within 8 weeks prior to Screening, and remaining stable until baseline.
- •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).
排除标准
- •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.
- •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.
- •Any vaccination received within 28 days prior to dosing (with few exceptions to be confirmed at screening).
- •Sensory CIDP, distal CIDP and focal CIDP variants.
- •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: --HBsAg. --Anti-HBc Ab; unless anti-HBs Ab are also positive, indicating natural immunity. --Anti-HCV antibodies. --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.
- •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.
- •Any country-related specific regulation that would prevent the participant from entering the study as defined by the protocol.
- •Any other neurological or systemic disease that can cause symptoms and signs interfering with treatment or outcome assessments.
- •Poorly controlled diabetes (HbA1c >7% at the Screening visit)
- •Serious infections requiring hospitalization within 30 days prior to Screening, 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 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.
- •Treatment with efgartigimod within 8 weeks prior to screening.
- •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.
- •Treatment with plasma exchange within 8 weeks prior to Screening.
- •Treatment within 3 months prior to dosing with immunosuppressive/ immunomodulator medication, or corticosteroids (except ≤20 mg/day of prednisone or equivalent 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.
- •Use of any specific complement system inhibitor (eg, eculizumab) within 12 weeks or 5 times the half-life of the product, whichever is longer, prior to Screening.
- •Prior treatment (any time) with total lymphoid irradiation or bone marrow transplantation.
结局指标
主要结局
Percentage of participants experiencing a response
Percentage of participants experiencing a response
Percentage of participants randomized to riliprubart who responded during part A and had a lasting response during the open-label treatment extension period.
Percentage of participants randomized to riliprubart who responded during part A and had a lasting response during the open-label treatment extension period.
次要结局
- Change from baseline in Rasch-built Overall Disability Scale (I-RODS) score
- Change from baseline in adjusted inflammatory neuropathy cause and treatment (INCAT) disability score
- Change from baseline in grip strength (kilopascals, dominant hand)
- Change from baseline in Medical Research Council Sum Score (MRC-SS)
- Change from baseline in the Rasch-built modified fatigue severity scale (RT-FSS)
- Percentage of participants experiencing a relapse
- Change from baseline in the EuroQol 5 Dimension, 5-Level Health Scale (EQ-5D-5L)
- Number of participants with TEAEs, including SAEs and AESIs for Part A.
- Number of participants with treatment-emergent ADA in participants treated with riliprubart
- Number of participants with TEAEs, including SAEs and AESIs
- Percentage of participants randomized to riliprubart experiencing a relapse
- Percentage of participants randomized to IVIg continuation experiencing a relapse
- Incidence and titer of anti-drug antibodies (ADA) during open-label treatment and follow-up.
- Change from baseline in I-RODS
- Change from baseline in adjusted INCAT score
- Change from baseline in grip strength (kilopascals; dominant hand)
- Change from baseline in MRC-SS
- Change from baseline in RT-FSS
- Change from baseline in EQ-5D-5L score
- Percentage of participants randomized to riliprubart who experienced a response at Week 48 without prior response in Part A (delayed response)
- Percentage of participants randomized to IVIg continuation who experience a response
研究者
Clinical Sciences and Operations
Scientific
Sanofi-Aventis Recherche & Developpement
研究点 (33)
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