To Assess Efficacy and Safety of Batoclimab in Adult Participants With Active CIDP
Study Details
Study Description
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 a 4-week Screening Phase, an up to 12-week Washout Phase, a 12-week Randomized Treatment Phase (Period 1), an up to 24-week Randomized Withdrawal Phase (Period 2), a 4-week Safety follow-up for participants not entering Long-Term Extension (LTE), and a 52-week LTE Phase. The total study duration will be up to 104 weeks. Eligible participants will be assigned to one of three cohorts (A, B, C) based upon their CIDP treatment at the time of screening.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment Period 1: Cohort A, Dose 1
|
Drug: Batoclimab 680 milligrams (mg) subcutaneous (SC) weekly
Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody
Other Names:
|
| Experimental: Treatment Period 1: Cohort A, Dose 2
|
Drug: Batoclimab 340 mg SC weekly
Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody
Other Names:
|
| Experimental: Treatment Period 1: Cohort B, Dose 1
|
Drug: Batoclimab 680 milligrams (mg) subcutaneous (SC) weekly
Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody
Other Names:
|
| Experimental: Treatment Period 1: Cohort B, Dose 2
|
Drug: Batoclimab 340 mg SC weekly
Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody
Other Names:
|
| Experimental: Treatment Period 1: Cohort C, Dose 1
|
Drug: Batoclimab 680 milligrams (mg) subcutaneous (SC) weekly
Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody
Other Names:
|
| Experimental: Treatment Period 1: Cohort C, Dose 2
|
Drug: Batoclimab 340 mg SC weekly
Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody
Other Names:
|
| Experimental: Withdrawal Period 2: Cohort A, Dose 1
|
Drug: Batoclimab 340 mg SC weekly
Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody
Other Names:
|
| Experimental: Withdrawal Period 2: Cohort A, Dose 2
|
Drug: Placebo
Matching placebo SC
|
| Experimental: Withdrawal Period 2: Cohort B, Dose 1
|
Drug: Batoclimab 340 mg SC weekly
Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody
Other Names:
|
| Experimental: Withdrawal Period 2: Cohort B, Dose 2
|
Drug: Placebo
Matching placebo SC
|
| Experimental: Withdrawal Period 2: Cohort C, Dose 1
|
Drug: Batoclimab 340 mg SC weekly
Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody
Other Names:
|
| Experimental: Withdrawal Period 2: Cohort C, Dose 2
|
Drug: Placebo
Matching placebo SC
|
| Experimental: LTE Phase: With Relapse in Period 2: Dose 1 and Dose 2
|
Drug: Batoclimab 680 milligrams (mg) subcutaneous (SC) weekly
Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody
Other Names:
Drug: Batoclimab 340 mg SC weekly
Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody
Other Names:
|
| Experimental: LTE Phase: Without Relapse in Period 2: Dose 2
|
Drug: Batoclimab 340 mg SC weekly
Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Period 2, Cohort A: Percentage of participants who remain relapse-free at Week 36 [Week 36]
Relapse is defined as a worsening (increase) of >= 1 point on the adjusted inflammatory neuropathy cause and treatment (Adj INCAT) score at any time point during Period 2 relative to Period 2 Baseline which is sustained at a Follow-Up visit 1 week later.
Secondary Outcome Measures
- 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 Baseline in Adj INCAT score [Baseline (Week 12) and up to Week 36]
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 the 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 the INCAT disability score with the 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.
- Period 2, Cohort A: Change from Baseline in Inflammatory Rasch-built Overall Disability Scale (I-RODS) [Baseline (Week 12) and up to Week 36]
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.
- Period 2, Cohort A: Change from Baseline in Mean grip strength [Baseline (Week 12) and up to Week 36]
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.
- Period 2, Cohort A: Change from Baseline in Medical Research Council (MRC) Sum Score [Baseline (Week 12) and up to Week 36]
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.
- Period 2, Cohort A: Change from Baseline in Overall Neuropathy Limitations Scale (ONLS) [Baseline (Week 12) and up to Week 36]
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.
- Period 2, Cohorts A and B combined: Change from Baseline in Adj INCAT score [Baseline (Week 12) and up to Week 36]
- Period 2, Cohorts A and B combined: Change from Baseline in I-RODS [Baseline (Week 12) and up to Week 36]
- Period 2, Cohorts A and B combined: Change from Baseline in Mean Grip Strength [Baseline (Week 12) and up to Week 36]
- Period 2, Cohorts A and B combined: Change from Baseline in MRC sum score [Baseline (Week 12) and up to Week 36]
- Period 2, Cohorts A and B combined: Change from Baseline in ONLS [Baseline (Week 12) and up to Week 36]
- Period 2, All Cohorts combined: Percentage of participants who remain relapse-free at Week 36 [Week 36]
- Periods 1, 2, and LTE phase: Number of participants with Treatment-emergent adverse events (TEAEs), Serious adverse events (SAEs), Adverse events (AEs) leading to study discontinuation [Day 1 (Period 1) up to Week 52 of LTE phase (Week L52); overall timeframe of up to 88 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) Guideline on the Diagnosis and Treatment of CIDP. Clinical criteria for typical CIDP and variants are as follows (either criteria 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
-
Have electrodiagnostic test results supporting the diagnosis of CIDP in accordance with the EAN/PNS Guideline on the Diagnosis and Treatment of CIDP (either criteria 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 more than 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.
Additional inclusion criteria are defined in the protocol.
Exclusion Criteria:
-
Have presence 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 the 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:
-
Diagnosis of DM pre-dates the diagnosis of CIDP
-
Has ever required daily insulin therapy
-
Duration of DM is 5 years or greater
-
Has evidence of microvascular complications of DM including retinopathy or nephropathy
-
Have a history of myelopathy or evidence of central demyelination.
-
Are receiving chronic oral corticosteroids monotherapy at a dose > 40 mg/day or < 20 mg/day prednisolone/prednisone or its equivalent at the Screening Visit.
-
Are receiving chronic oral corticosteroid at a dose > 10 mg/day prednisone or equivalent in combination with immunoglobulin therapy or PLEX at the Screening Visit.
Additional exclusion criteria are defined in the protocol.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Site Number -1600 | Boca Raton | Florida | United States | 33487 |
| 2 | Site Number -1601 | Austin | Texas | United States | 78759 |
Sponsors and Collaborators
- Immunovant Sciences GmbH
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IMVT-1401-2401