To Assess Efficacy and Safety of Batoclimab in Adult Participants With Active CIDP

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
A Phase 2b, Multi-center, Randomized, Quadruple-blind, Placebo-controlled Study of Batoclimab Treatment in Adult Participants With Active Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Conditions
-----------------
Chronic Inflammatory Demyelinating Polyneuropathy

Intervention / Treatment
-----------------
* Drug: Batoclimab 680 milligrams (mg) subcutaneous (SC) weekly
* Drug: Batoclimab 340 mg SC weekly
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Period 1: Cohort A, Dose 1<br> | Drug: Batoclimab 680 milligrams (mg) subcutaneous (SC) weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Experimental: Treatment Period 1: Cohort A, Dose 2<br> | Drug: Batoclimab 340 mg SC weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Experimental: Treatment Period 1: Cohort B, Dose 1<br> | Drug: Batoclimab 680 milligrams (mg) subcutaneous (SC) weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Experimental: Treatment Period 1: Cohort B, Dose 2<br> | Drug: Batoclimab 340 mg SC weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Experimental: Treatment Period 1: Cohort C, Dose 1<br> | Drug: Batoclimab 680 milligrams (mg) subcutaneous (SC) weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Experimental: Treatment Period 1: Cohort C, Dose 2<br> | Drug: Batoclimab 340 mg SC weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Experimental: Treatment Period 1: Cohort D, Dose 1<br> | Drug: Batoclimab 680 milligrams (mg) subcutaneous (SC) weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Experimental: Treatment Period 1: Cohort D, Dose 2<br> | Drug: Batoclimab 340 mg SC weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Experimental: Withdrawal Period 2: Cohort A, Dose 2<br> | Drug: Batoclimab 340 mg SC weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Experimental: Withdrawal Period 2: Cohort A, Placebo<br> | Drug: Placebo<br>* Matching placebo SC<br>|
| Experimental: Withdrawal Period 2: Cohort B, Dose 2<br> | Drug: Batoclimab 340 mg SC weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Experimental: Withdrawal Period 2: Cohort B, Placebo<br> | Drug: Placebo<br>* Matching placebo SC<br>|
| Experimental: Withdrawal Period 2: Cohort C, Dose 2<br> | Drug: Batoclimab 340 mg SC weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Experimental: Withdrawal Period 2: Cohort C, Placebo<br> | Drug: Placebo<br>* Matching placebo SC<br>|
| Experimental: Withdrawal Period 2: Cohort D, Dose 2<br> | Drug: Batoclimab 340 mg SC weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Experimental: Withdrawal Period 2: Cohort D, Placebo<br> | Drug: Placebo<br>* Matching placebo SC<br>|
| Experimental: LTE Period: With Relapse in Period 2: Dose 1 and Dose 2<br>Participants will receive Dose 1 for the initial 4 weeks only and Dose 2 for the remaining 48 weeks. | Drug: Batoclimab 680 milligrams (mg) subcutaneous (SC) weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;Drug: Batoclimab 340 mg SC weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Experimental: LTE Period: Without Relapse in Period 2: Dose 2<br>Participants will receive Dose 2 for all 52 weeks. | Drug: Batoclimab 340 mg SC weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Period 2, Cohort A: Proportion of participants who remain relapse-free at 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. | Week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Period 2, Cohort A: Time to first relapse relative to Period 2 Baseline |  | Baseline (Week 12) to Week 36 | 
| 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: Change from Period 2 Baseline in Inflammatory Rasch-built Overall Disability Scale (I-RODS) | The I-RODS for immune-mediated peripheral neuropathies is a patient-based linearly weighted scale that captures activity and social participation limitations in patients with CIDP. The assessment consists of a 24-question instrument that addresses upper and lower limb tasks that range in difficulty from reading a book and eating to standing and running. Answers are scored on a scale of 0-2 (complete disability to no disability) and the raw scores are then transformed into a final score ranging from 0-100. | Baseline (Week 12) and up to Week 36 | 
| Period 2, Cohort A: Change from Period 2 Baseline in Mean grip strength | Mean Grip strength provides an objective, quantitative and immediate assessment of strength impairment. The Jamar dynamometer and the Martin vigorimeter are both commonly used to assess mean grip strength. | Baseline (Week 12) and up to Week 36 | 
| Period 2, Cohort A: Change from Period 2 Baseline in Medical Research Council (MRC) Sum Score | The MRC sum score is a standardized methodology for objectively assessing and reporting muscle function. Six muscle groups are assessed bilaterally, and each scored on a scale of 0 (no visible contraction) to 5 (normal) yielding a sum ranging from 0 (paralysis) to 60 (normal strength). Higher scores indicate normal muscle strength. | Baseline (Week 12) and up to Week 36 | 
| Period 2, Cohort A: Change from Period 2 Baseline in Overall Neuropathy Limitations Scale (ONLS) | The ONLS is a scale that focuses on upper and lower limb functions and was designed to assess the limitations of participants with immune-mediated peripheral neuropathies. This scale is completed by adding the total of the arm grade from zero point (less limitation) to 5 points (most limitation) and leg grade from zero point (less limitation) to 7 points (more limitation) yielding a total score of 0 (no disability) to 12 (maximum disability). Lower values in the ONLS indicate a better clinical condition. | 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 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 Mean Grip Strength |  | 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 | 
| Period 2, Cohorts A, B, and C: Proportion of participants who remain relapse-free at Week 36 |  | Week 36 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic Inflammatory Demyelinating Polyneuropathy, IMVT-1401, Monoclonal antibody, Autoimmune disorders