| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) | |
| E.1.1.1 | Medical condition in easily understood language | | Inflammation of peripheral nervous system | |
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10077384 | | E.1.2 | Term | Chronic inflammatory demyelinating polyneuropathy | | E.1.2 | System Organ Class | 100000004852 | |
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | Period 2/ Cohort A:
To evaluate the efficacy of batoclimab compared to placebo in maintaining clinical response as assessed by adjusted inflammatory neuropathy cause and treatment (Adj INCAT) score in participants receiving immune globulin (IVIg or SCIg) or plasma exchange (PLEX) treatment for CIDP at the time of screening | |
| E.2.2 | Secondary objectives of the trial | Period 2/ Cohort A:
-To evaluate the efficacy of batoclimab compared to placebo in maintaining clinical response in participants receiving
immune globulin (IVIg or SCIg) or PLEX treatment for CIDP at the time of screening
Period 2/ Cohort A and B combined:
-To evaluate the efficacy of batoclimab compared to placebo in maintaining clinical response in participants receiving
any CIDP treatment at the time of screening
Period 2/ All 3 cohorts combined:
-To evaluate the efficacy of batoclimab compared to placebo in maintaining clinical response regardless of CIDP
treatment history
| |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | 1. Are > 18 years at the Screening Visit.
2. 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 the Diagnosis and Treatment of CIDP. Clinical criteria for typical CIDP and variants are as follows (either criteria must be met):
a. 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
b. 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
3. 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):
a. Motor nerve conduction criteria strongly supportive of demyelination.
b. 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.
4. Additional inclusion criteria are defined in the protocol.
| |
| E.4 | Principal exclusion criteria | 1. Have presence of immunoglobulin M (IgM) paraproteinemia with or without anti-myelin-associated-glycoprotein antibodies.
2. 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.
3. Have polyneuropathy of causes other than CIDP including but not limited to:
a. Multifocal motor neuropathy
b. Hereditary demyelinating neuropathy
c. Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin change syndromes (i.e., POEMS)
d. Lumbosacral radiculoplexus neuropathy
e. Systemic illnesses including vitamin deficiency syndromes and paraneoplastic neuropathies
f. Drug- or toxin-induced
4. Have diabetes mellitus (DM) and meets any of the following criteria:
a. Diagnosis of DM pre-dates the diagnosis of CIDP
b. Has ever required daily insulin therapy
c. Duration of DM is 5 years or greater
d. Has evidence of microvascular complications of DM including retinopathy or nephropathy
5. Have a history of myelopathy or evidence of central demyelination.
6. 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.
7. 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.
8. Additional exclusion criteria are defined in the protocol.
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | Period 2/ Cohort A:
Proportion of participants who remain relapse-free at Week 36 where relapse is defined as a worsening (increase) of ≥ 1 point
on the 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. | |
| E.5.1.1 | Timepoint(s) of evaluation of this end point | |
| E.5.2 | Secondary end point(s) | Period 2/ Cohort A:
-Time to first relapse relative to Period 2 baseline
- Change from Period 2 baseline to Week 36 in:
o Adj INCAT score
o Inflammatory Rasch-built Overall Disability Scale (I-RODS)
o Mean Grip Strength
o Medical Research Council (MRC) Sum Score
o Overall Neuropathy Limitations Scale (ONLS)
Period 2/ Cohort A and B combined:
-Change from Period 2 baseline to Week 36 in:
o Adj INCAT score
o I-RODS
o Mean Grip Strength
o MRC Sum Score
o ONLS
Period 2/ All 3 cohorts combined:
-Proportion of participants who remain relapse-free at Week 36 | |
| E.5.2.1 | Timepoint(s) of evaluation of this end point | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 | The trial involves single site in the Member State concerned | Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 60 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned | | Argentina | | Australia | | Brazil | | Canada | | Israel | | Japan | | Mexico | | Peru | | United States | | Switzerland | | Serbia | | Austria | | Belgium | | Bulgaria | | Croatia | | Czechia | | Denmark | | Finland | | France | | Germany | | Greece | | Hungary | | Ireland | | Italy | | Netherlands | | Norway | | Poland | | Portugal | | Slovakia | | Spain | | Sweden | | Korea, Republic of | | United Kingdom | | Romania | |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | | The end of study is defined as the date of the last visit of the last participant in the study or last scheduled procedure shown in the Schedule of Activities (SoA) for the last participant in the trial. | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
