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

Chronic Inflammatory Demyelinating Polyneuropathy Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05581199
• Other study ID #: IMVT-1401-2401
• Status: Recruiting
• Phase: Phase 2
• Start date: December 15, 2022
• Est. completion date: January 2027

Study information

• Verified date: June 2024
• Source: Immunovant Sciences GmbH
• Contact: Central Study Contact
• Phone: 18007970414
• Email: clinicaltrials[@]immunovant.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 277
• Est. completion date: January 2027
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

All Cohorts:

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 Diagnosis and Treatment of CIDP. Clinical criteria for typical CIDP and variants are as follows (either criterion must be met):

1. 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

2. 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:

3. 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:

1. Motor nerve conduction criteria strongly supportive of demyelination.

2. 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:

4. 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:

5. 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:

1. Have current or prior history 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 Diagnosis and Treatment of CIDP.

3. Have polyneuropathy of causes other than CIDP including but not limited to:

1. Multifocal motor neuropathy

2. Hereditary demyelinating neuropathy

3. Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin change syndromes (i.e., POEMS)

4. Lumbosacral radiculoplexus neuropathy

5. Systemic illnesses including vitamin deficiency syndromes and paraneoplastic neuropathies

6. Drug- or toxin-induced

4. Have diabetes mellitus (DM) and meets any of the following criteria:

1. Does not meet inclusion criteria 2(a) and 3(a).

2. In the opinion of the Investigator, there is evidence of poorly controlled DM preceding the diagnosis of CIDP.

3. In the opinion of the Investigator, there is evidence of poorly controlled DM at screening.

5. Have a history of myelopathy or evidence of central demyelination.

6. Are receiving chronic oral corticosteroids monotherapy at a dose > 40 mg/day prednisolone/prednisone or its equivalent at the Screening Visit.

7. 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.

Related Conditions & MeSH terms

• Chronic Inflammatory Demyelinating Polyneuropathy
• Polyneuropathies
• Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

Intervention

Drug:
• Batoclimab 680 milligrams (mg) subcutaneous (SC) weekly
Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody
• Batoclimab 340 mg SC weekly
Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody
• Placebo
Matching placebo SC

Locations

Country	Name	City	State
Argentina	Site Number - 7750	Ciudad Autónoma de Buenos Aires
Argentina	Site Number - 7751	Rosario	Santa Fe
Argentina	Site Number - 7753	Rosario	Santa Fe
Argentina	Site Number - 7752	Tucumán	Tucuman
Belgium	Site Number - 4681	Gent	Oost-Vlaanderen
Belgium	Site Number - 4680	Leuven	Vlaams Brabant
Brazil	Site Number - 9103	Brasília	Distrito Federal
Brazil	Site Number - 9101	Curitiba	Paraná
Brazil	Site Number - 9100	Ribeirão Preto	São Paulo
Bulgaria	Site Number - 9110	Sofia	Sofia-Grad
Bulgaria	Site Number - 9111	Sofia	Sofia-Grad
Denmark	Site Number - 4740	Copenhagen
Finland	Site Number - 3241	Turku	Varsinais-Suomi
Germany	Site Number - 6705	Bochum	Nordrhein-Westfalen
Germany	Site Number - 6700	Dresden	Sachsen
Germany	Site Number - 6702	Leipzig	Sachsen
Germany	Site Number - 6704	München	Bayern
Greece	Site Number - 6343	Alexandroupolis	Evros
Greece	Site Number - 6344	Athens	Attiki
Greece	Site Number - 6345	Athens	Attiki
Greece	Site Number - 6342	Heraklion	Irakleio
Greece	Site Number - 6346	Ioánnina	Ioannina
Greece	Site Number - 6347	Larisa
Greece	Site Number -6341	Patras	Achaïa
Italy	Site Number - 6301	Bergamo	Lombardia
Italy	Site Number -6305	Bologna	Emilia-Romagna
Italy	Site Number -6302	Gussago	Brescia
Italy	Site Number - 6307	Milano	Lombardia
Italy	Site Number - 6300	Pavia
Italy	Site Number - 6303	Pisa	Toscana
Italy	Site Number - 6309	Roma	Lazio
Italy	Site Number -6306	Roma	Lazio
Italy	Site Number - 6308	Siena	Toscana
Italy	Site Number - 6304	Udine	Friuli-Venezia Giulia
Korea, Republic of	Site Number - 9900	Seoul
Korea, Republic of	Site Number - 9901	Seoul
Norway	Site Number -6491	Oslo
Poland	Site Number - 3211	Bydgoszcz	Kujawsko-pomorskie
Poland	Site Number -3203	Bydgoszcz	Województwo Kujawsko-pomorskie
Poland	Site Number - 3205	Gdansk	Pomorskie
Poland	Site Number -3201	Katowice	Slaskie
Poland	Site Number - 3209	Krakow	Malopolskie
Poland	Site Number -3200	Krakow	Malopolskie
Poland	Site Number - 3208	Kraków	Malopolskie
Poland	Site Number - 3210	Lublin	Lubelskie
Poland	Site Number -3206	Lublin	Lubelskie
Poland	Site Number -3202	Mazurki	Lubelskie
Poland	Site Number - 3207	Poznan	Wielkopolskie
Poland	Site Number - 3204	Wroclaw	Dolnoslaskie
Portugal	Site Number - 3743	Almada	Setubal
Portugal	Site Number - 3741	Lisboa
Portugal	Site Number - 3744	Porto
Portugal	Site Number - 3742	Senhora Da Hora	Porto
Portugal	Site Number - 3745	Vila Nova De Gaia	Porto
Romania	Site Number - 8406	Bucharest	Bucuresti
Romania	SIte Number - 8400	Constanta
Romania	Site Number - 8401	Targu Mures	Mures
Romania	Site Number - 8403	Timisoara	Timis
Serbia	Site Number - 8502	Belgrade
Serbia	Site Number - 8501	Beograd	Belgrade
Serbia	Site Number - 8500	Niš
Serbia	Site Number - 8503	Novi Sad
Slovakia	Site Number - 8600	Liptovský Mikuláš
Slovakia	Site Number - 8601	Martin
Slovakia	Site Number - 8603	Prešov
Slovakia	Site Number - 8602	Trnava
Spain	Site Number - 3703	Barcelona
Spain	Site Number - 3701	Hospitalet de Llobregat	Barcelona
Spain	Site Number -3700	San Sebastián	Gipuzkoa
Spain	Site Number - 3704	Sant Cugat Del Vallès	Barcelona
Sweden	Site Number -4891	Göteborg	Vastra Gotalands Lan
United Kingdom	Site Number - 7405	Cambridge	Cambridgeshire
United Kingdom	Site Number - 7404	Glasgow	Lanarkshire
United Kingdom	Site Number - 7400	Manchester
United Kingdom	Site Number - 7403	Preston	Lancashire
United Kingdom	Site Number - 7402	Southampton	Hampshire
United States	Site Number - 1625	Aurora	Colorado
United States	Site Number -1601	Austin	Texas
United States	Site Number - 1600	Boca Raton	Florida
United States	Site Number -1618	Carlsbad	California
United States	Site Number - 1610	Charlotte	North Carolina
United States	Site Number - 1636	Fort Collins	Colorado
United States	Site Number - 1606	Houston	Texas
United States	Site Number - 1609	Jacksonville	Florida
United States	Site Number - 1602	Kansas City	Kansas
United States	Site Number - 1621	New Haven	Connecticut
United States	Site Number - 1605	New York	New York
United States	Site Number - 1611	Nicholasville	Kentucky
United States	Site Number -1607	O'Fallon	Illinois
United States	Site Number - 1619	Orange	California
United States	Site Number - 1629	Orlando	Florida
United States	Site Number - 1631	Orlando	Florida
United States	Site Number -1617	Ormond Beach	Florida
United States	Site Number - 1623	Philadelphia	Pennsylvania
United States	Site Number - 1624	Philadelphia	Pennsylvania
United States	Site Number -1620	Port Charlotte	Florida
United States	Site Number - 1614	Portland	Oregon
United States	Site Number - 1627	Richmond	Virginia
United States	Site Number - 1633	Rockledge	Florida
United States	Site Number - 1604	Saint Petersburg	Florida
United States	Site Number - 1628	San Antonio	Texas
United States	Site Number - 1608	San Francisco	California
United States	Site Number - 1603	Scottsdale	Arizona
United States	Site Number - 1630	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Immunovant Sciences GmbH

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Bulgaria,  Denmark,  Finland,  Germany,  Greece,  Italy,  Korea, Republic of,  Norway,  Poland,  Portugal,  Romania,  Serbia,  Slovakia,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Period 2, Cohort A: Time to first relapse relative to Period 2 Baseline		Baseline (Week 12) to Week 36
Secondary	Period 2, Cohort A: Change from Period 2 Baseline in Adj INCAT score		Baseline (Week 12) and up to Week 36
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Period 2, Cohorts A and B combined: Change from Period 2 Baseline in Adj INCAT score		Baseline (Week 12) and up to Week 36
Secondary	Period 2, Cohorts A and B combined: Change from Period 2 Baseline in I-RODS		Baseline (Week 12) and up to Week 36
Secondary	Period 2, Cohorts A and B combined: Change from Period 2 Baseline in Mean Grip Strength		Baseline (Week 12) and up to Week 36
Secondary	Period 2, Cohorts A and B combined: Change from Period 2 Baseline in MRC sum score		Baseline (Week 12) and up to Week 36
Secondary	Period 2, Cohorts A and B combined: Change from Period 2 Baseline in ONLS		Baseline (Week 12) and up to Week 36
Secondary	Period 2, Cohorts A, B, and C: Proportion of participants who remain relapse-free at Week 36		Week 36