A Phase 2b, Multi-center, Randomized, Quadruple-blind, Placebo-controlled Study of Batoclimab Treatment in Adult Participants With Active Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 94
- 试验地点
- 98
- 主要终点
- Period 2, Cohort A: Proportion of participants who remain relapse-free at Week 36
研究概览
简要总结
This is a multi-center, randomized, quadruple-blind, placebo-controlled study to evaluate the efficacy and safety of batoclimab in adult participants with active CIDP. The study includes an up to 4-week Screening Period, an up to 12-week Washout Period, a 12-week Randomized Treatment Period (Period 1), an up to 24-week Randomized Withdrawal Period (Period 2), an up to 52-week Long-term Extension (LTE) Period (optional), and Safety Follow-up 4 weeks after the last dose of study treatment. The total study duration will be up to approximately 109 weeks. Eligible participants will be assigned to one of four cohorts based upon their baseline CIDP treatment (Cohorts A and D - immunoglobulin [Ig] or plasma exchange [PLEX]; Cohort B - corticosteroids; Cohort C - naive or untreated in previous 3-24 months) and whether they meet diagnosis according to the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) criteria (Cohorts A, B, and C) or clinical criteria only (Cohort D) at the time of screening.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- •All Cohorts:
- •Are >= 18 years at the Screening Visit.
- •Have met clinical diagnostic criteria for typical CIDP, or one of the following CIDP variants: multifocal CIDP, focal CIDP, or motor CIDP in accordance with the EAN/PNS Guideline on Diagnosis and Treatment of CIDP. Clinical criteria for typical CIDP and variants are as follows (either criterion must be met):
- •Typical CIDP: All the following:
- •Progressive or relapsing, symmetric, proximal, and distal muscle weakness of upper and lower limbs, and sensory involvement of at least two limbs (at any point in the disease course)
- •Developing over at least 8 weeks
- •Absent or reduced tendon reflexes in all limbs
- •CIDP variants: One of the following, but otherwise as in typical CIDP (tendon reflexes may be normal in unaffected limbs):
- •Multifocal CIDP: documented sensory loss and muscle weakness in a multifocal pattern, usually asymmetric, upper limb predominant
- •Focal CIDP: sensory loss and muscle weakness in only one limb
- •Motor CIDP: motor symptoms and signs without sensory involvement
- •Cohorts A and B:
- •Have electrodiagnostic test results supporting the diagnosis of CIDP in accordance with the EAN/PNS Guideline on Diagnosis and Treatment of CIDP; for Cohorts A and B, either criterion must be met:
- •Motor nerve conduction criteria strongly supportive of demyelination.
- •Motor nerve conduction criteria weakly supportive of demyelination and 2 or more of the following additional diagnostic criteria:
- •Objective improvement to an empiric trial of therapy with immunoglobulin treatment, plasma exchange (PLEX), or corticosteroids.
- •Diagnostic imaging by ultrasound or magnetic resonance imaging (MRI) supporting the diagnosis of CIDP by demonstrating nerve enlargement.
- •Cerebrospinal fluid (CSF) demonstrating albuminocytologic dissociation (i.e., elevated CSF protein level [defined as > 70 milligrams per deciliter {mg/dL} or > 10 mg/dL greater than years of age for those aged 60 years and over] with normal CSF white blood cell [WBC] level).
- •Nerve biopsy demonstrating features supporting the diagnosis of CIDP, such as edema, demyelination, and/or onion bulb formation.
- •Cohort C only:
- •Have a diagnosis of CIDP in accordance with the EAN/PNS Guideline on Diagnosis and Treatment of CIDP based on clinical criteria and motor nerve conduction criteria strongly supportive of demyelination (i.e., motor nerve conduction criteria weakly supportive of demyelination is insufficient diagnostic evidence for admission to Cohort C).
- •Cohort D only:
- •Have met only clinical diagnostic criteria for typical CIDP, or one of the following CIDP variants: multifocal CIDP, focal CIDP, or motor CIDP in accordance with the EAN/PNS Guideline on Diagnosis and Treatment of CIDP. Either inclusion criterion 2(a) or 2(b) must be met.
- •Additional inclusion criteria are defined in the protocol.
排除标准
- •All Cohorts:
- •Have current or prior history of immunoglobulin M (IgM) paraproteinemia with or without anti-myelin-associated-glycoprotein antibodies.
- •Have Distal CIDP, Sensory CIDP or are suspected of having a diagnosis of auto-immune nodopathy in accordance with the EAN/PNS Guideline on Diagnosis and Treatment of CIDP.
- •Have polyneuropathy of causes other than CIDP including but not limited to:
- •Multifocal motor neuropathy
- •Hereditary demyelinating neuropathy
- •Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin change syndromes (i.e., POEMS)
- •Lumbosacral radiculoplexus neuropathy
- •Systemic illnesses including vitamin deficiency syndromes and paraneoplastic neuropathies
- •Drug- or toxin-induced
- •Have diabetes mellitus (DM) and meets any of the following criteria:
- •Does not meet inclusion criteria 2(a) and 3(a).
- •In the opinion of the Investigator, there is evidence of poorly controlled DM preceding the diagnosis of CIDP.
- •In the opinion of the Investigator, there is evidence of poorly controlled DM at screening.
- •Have a history of myelopathy or evidence of central demyelination.
- •Are receiving chronic oral corticosteroids monotherapy at a dose > 40 mg/day prednisolone/prednisone or its equivalent at the Screening Visit.
- •Are receiving chronic oral corticosteroid at a dose > 10 mg/day prednisolone/prednisone or equivalent in combination with immunoglobulin therapy or PLEX at the Screening Visit.
- •Additional exclusion criteria are defined in the protocol.
研究组 & 干预措施
Treatment Period 1: Cohort A, Dose 1
干预措施: Batoclimab 680 milligrams (mg) subcutaneous (SC) weekly (Drug)
Withdrawal Period 2: Cohort C, Placebo
干预措施: Placebo (Drug)
Withdrawal Period 2: Cohort B, Placebo
干预措施: Placebo (Drug)
Withdrawal Period 2: Cohort D, Placebo
干预措施: Placebo (Drug)
Withdrawal Period 2: Cohort A, Placebo
干预措施: Placebo (Drug)
Treatment Period 1: Cohort B, Dose 1
干预措施: Batoclimab 680 milligrams (mg) subcutaneous (SC) weekly (Drug)
Treatment Period 1: Cohort D, Dose 1
干预措施: Batoclimab 680 milligrams (mg) subcutaneous (SC) weekly (Drug)
Treatment Period 1: Cohort A, Dose 2
干预措施: Batoclimab 340 mg SC weekly (Drug)
Treatment Period 1: Cohort B, Dose 2
干预措施: Batoclimab 340 mg SC weekly (Drug)
Treatment Period 1: Cohort C, Dose 1
干预措施: Batoclimab 680 milligrams (mg) subcutaneous (SC) weekly (Drug)
Treatment Period 1: Cohort C, Dose 2
干预措施: Batoclimab 340 mg SC weekly (Drug)
Treatment Period 1: Cohort D, Dose 2
干预措施: Batoclimab 340 mg SC weekly (Drug)
Withdrawal Period 2: Cohort A, Dose 2
干预措施: Batoclimab 340 mg SC weekly (Drug)
Withdrawal Period 2: Cohort B, Dose 2
干预措施: Batoclimab 340 mg SC weekly (Drug)
Withdrawal Period 2: Cohort C, Dose 2
干预措施: Batoclimab 340 mg SC weekly (Drug)
Withdrawal Period 2: Cohort D, Dose 2
干预措施: Batoclimab 340 mg SC weekly (Drug)
LTE Period: With Relapse in Period 2: Dose 1 and Dose 2
Participants will receive Dose 1 for the initial 4 weeks only and Dose 2 for the remaining 48 weeks.
干预措施: Batoclimab 680 milligrams (mg) subcutaneous (SC) weekly (Drug)
LTE Period: With Relapse in Period 2: Dose 1 and Dose 2
Participants will receive Dose 1 for the initial 4 weeks only and Dose 2 for the remaining 48 weeks.
干预措施: Batoclimab 340 mg SC weekly (Drug)
LTE Period: Without Relapse in Period 2: Dose 2
Participants will receive Dose 2 for all 52 weeks.
干预措施: Batoclimab 340 mg SC weekly (Drug)
结局指标
主要结局
Period 2, Cohort A: Proportion of participants who remain relapse-free at Week 36
时间窗: Week 36
Relapse is defined as a worsening (increase) of \>=1 point on adjusted inflammatory neuropathy cause and treatment (AdjINCAT) score at any time point during Period 2 relative to Period 2 Baseline which is sustained at a Follow-Up visit 1 week later. The INCAT disability scale is a widely used and validated efficacy assessment of neurologic dysfunction in CIDP. Upper and lower limb dysfunction are each separately assessed on a scale of 0-5 and results are summed together for a total composite score of 0-10. Higher scores represent greater disability. The Adj INCAT disability score is identical to INCAT disability score with exception that changes in upper limb function from 0 (normal) to 1 (minor symptoms) and vice versa are excluded since minor symptoms in the fingers, which are implied by an upper limb score of 1, are not considered clinically significant in all participants. The Adj INCAT disability score will be used for participant selection and measurement of clinical response.
次要结局
- Period 2, Cohort A: Change from Period 2 Baseline in Adj INCAT score(Baseline (Week 12) and up to Week 36)
- Period 2, Cohort A: Time to first relapse relative to Period 2 Baseline(Baseline (Week 12) to Week 36)
- Period 2, Cohorts A and B combined: Change from Period 2 Baseline in Mean Grip Strength(Baseline (Week 12) and up to Week 36)
- Period 2, Cohort A: Change from Period 2 Baseline in Inflammatory Rasch-built Overall Disability Scale (I-RODS)(Baseline (Week 12) and up to Week 36)
- Period 2, Cohorts A and B combined: Change from Period 2 Baseline in Adj INCAT score(Baseline (Week 12) and up to Week 36)
- Period 2, Cohorts A, B, and C: Proportion of participants who remain relapse-free at Week 36(Week 36)
- Period 2, Cohort A: Change from Period 2 Baseline in Medical Research Council (MRC) Sum Score(Baseline (Week 12) and up to Week 36)
- Period 2, Cohort A: Change from Period 2 Baseline in Mean grip strength(Baseline (Week 12) and up to Week 36)
- Period 2, Cohort A: Change from Period 2 Baseline in Overall Neuropathy Limitations Scale (ONLS)(Baseline (Week 12) and up to Week 36)
- Period 2, Cohorts A and B combined: Change from Period 2 Baseline in I-RODS(Baseline (Week 12) and up to Week 36)
- Period 2, Cohorts A and B combined: Change from Period 2 Baseline in MRC sum score(Baseline (Week 12) and up to Week 36)
- Period 2, Cohorts A and B combined: Change from Period 2 Baseline in ONLS(Baseline (Week 12) and up to Week 36)