Clinical trial NCT06290128: A Study to Test the Effects and Safety of Riliprubart in People With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) for Which the Usual Treatments do Not Work
Official title: A Phase 3, Double-blind, Placebo-controlled Study Evaluating Efficacy and Safety of Riliprubart in Participants With Refractory Chronic Inflammatory Demyelinating Polyneuropathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Polyneuropathy, Inflammatory Demyelinating, Chronic
Keywords: Autoimmune Diseases, Neurologic
Autoimmune Disorders, Nervous System
Peripheral Nerves Disease
Nervous System Diseases
Neurologic Disorders
Neurological Disorders
Complement Inhibitor
Complement Inhibitors
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2024-03-04
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a double-blind treatment in part A and open-label treatment in Part B.
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate efficacy of riliprubart compared to placebo in adult participants with CIDP whose disease is refractory to standard of care. The study duration will be for a maximum of 111 weeks including screening, treatment phases, and follow-up.


Eligibility criteria: Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

-Participant must have CIDP or possible CIDP criteria, based on European Academy of Neurology (EAN)/ Peripheral Nerve Society (PNS) Task Force CIDP guidelines, second revision (2021).

* Participant must have either typical CIDP, or one of the following two CIDP variants: motor CIDP (including motor predominant), multifocal CIDP (also known as Lewis Sumner Syndrome). Diagnosis must be confirmed by the adjudication committee.
* Participant must be refractory to either immunoglobulin therapy or corticosteroid therapy, as defined below.

  * Immunoglobulinrefractory subgroup: Historic evidence of failure or inadequate response to immunoglobulin therapy prior to screening, defined as no clinically meaningful improvement or persistent INCAT score ≥2 after a minimum of:

    * One dose of IVIg of 2 g/kg, followed by a second dose of 2 g/kg or two doses of 1 g/kg, with a separation of approximately 3 weeks between doses (each dose can be divided over 2 to 5 days), as indicated in the EAN/PNS 2021 guidelines OR
    * SCIg maintenance therapy with at least 0.2 g/kg weekly for 5 weeks
  * Corticosteroidrefractory subgroup:

Historic evidence of failure or inadequate response to corticosteroid therapy prior to screening, defined as no clinically meaningful improvement or persistent INCAT score ≥2 after a minimum of 12 weeks of corticosteroid therapy. Corticosteroid regimen can be daily oral prednisone/prednisolone, at least 60 mg, equivalent to methylprednisolone 48 mg, tapered over 6 to 8 months, or alternative regimens, e.g. pulsed high-dose corticosteroid treatment (40 mg/day oral dexamethasone or 500 mg/day IV methylprednisolone, each daily for 4 days per month for 6 months), as indicated in the EAN/PNS 2021 guidelines A clinically meaningful improvement is defined as one or more of the following:

* A ≥1 point decrease in adjusted INCAT disability score
* An increase in IRODS centile score ≥4 points
* An increase in MRC Sum score ≥3 points
* An improvement in hand grip strength of ≥8 kilopascals or
* Equivalent improvement based on information from medical records and per the Investigator's judgment

  * Participant has an adjusted INCAT score of 2 to 9

    --(a score of 2 should be exclusively from the leg disability component of INCAT).
  * Any allowed immunosuppressant drugs (azathioprine, cyclosporine, or mycophenolate mofetil) have been taken for ≥6 months at a stable dose for ≥3 months prior to Screening
  * Participant may be receiving low-dose oral corticosteroids (≤20 mg/day of prednisone \[or equivalent dose for other oral corticosteroids\]), but only if taken at a stable dose for ≥3 months prior to Screening
  * Participant must have active disease, defined by a CIDP disease activity score (CDAS) of ≥ 2 points at Screening
  * Participant must have documented vaccinations against encapsulated bacterial pathogens given within 5 years prior to Day 1 or initiated a minimum of 14 days prior to first dose of study intervention
  * All participants must agree to use contraception methods during and after the study as required.
  * Contraceptive use by men and women participating in the study should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

    * Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 55 weeks after the last dose of study medication:
* Refrain from donating or cryopreserving sperm PLUS
* Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR
* Must agree to use contraception/barrier as detailed below:

  ---- A male condom and an additional highly effective contraceptive method as described in the protocol.

  -- A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies:
* Is a woman of nonchildbearing potential (WONCBP) as defined by the protocol OR
* Is a woman of childbearing potential (WOCBP) and agrees to use a contraceptive method that is highly effective (with a failure rate of \<1% per year), as described in Appendix 10.4 Contraception and barrier guidance during the study intervention period (to be effective before starting the intervention) and for at least 55 weeks after the last administration of study intervention and agrees not to donate or cryopreserve eggs (ova, oocytes) for the purpose of reproduction during this period.

  * Body weight at Screening of 35 kg to 154 kg (77 to 340 lbs), inclusive

Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply:

* Polyneuropathy of other causes, including but not limited to: hereditary demyelinating neuropathies, neuropathies secondary to infection or systemic disease, diabetic neuropathy, drug- or toxin-induced neuropathies, multifocal motor neuropathy, polyneuropathy related to Immunoglobulin M (IgM) monoclonal gammopathy, POEMS syndrome, and lumbosacral radiculoplexus neuropathy.
* Sensory CIDP, Distal CIDP and focal CIDP variants.
* Any other neurological or systemic disease that can cause symptoms and signs interfering with treatment or outcome assessments
* Poorly controlled diabetes (HbA1c \>7%)
* Serious infections requiring hospitalization within 30 days prior to Screening and any active infection requiring treatment during screening or presence of a condition that may predispose the participant to increased risk of infection (eg, medical history such as known immunodeficiency or history of recurrent infections)
* Clinical diagnosis of Systemic Lupus Erythematosus (SLE) or family history of SLE. For a participant with an antinuclear antibody (ANA) titer ≥1:160 and a positive anti-double-stranded DNA (anti-dsDNA) at Screening, SLE diagnosis must be ruled out prior to enrollment.
* Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study. Specifically, history of any hypersensitivity reaction to riliprubart or its components or of a severe allergic or anaphylactic reaction to any humanized or murine monoclonal antibody.
* Any other clinically meaningful medical history or ongoing medical condition (as determined by the Investigator at Screening) that might impact benefitrisk assessment, jeopardize the safety of the participant, or compromise the quality of the data collected in this study; or history or presence of other significant concomitant illness that would adversely affect participation in this study, per Investigator's judgment.
* Documented history of attempted suicide over the 6 months prior to the Screening visit, presence of suicidal ideation of category 4 or 5 on CSSRS during screening, OR if in the Investigator's judgment, the participant is at risk for a suicide attempt.
* Evidence of CIDP worsening within the 6 weeks following a prior vaccination that, in the opinion of the Investigator, constituted a relapse
* Recent or planned major surgery that could confound the results of the trial or put the participant at undue risk
* Participant has received immunoglobulins (IVIg or SCIg) within 8 weeks prior to Screening
* Treatment with plasma exchange within the 8 weeks prior to Screening
* Prior treatment with riliprubart
* Prior treatment with (any time) with highly immunosuppressive/chemotherapeutic medications with sustained effects, eg, mitoxantrone, alemtuzumab, cladribine
* Prior treatment (any time) with total lymphoid irradiation or bone marrow transplantation
* Prior treatment with B-cell-depleting agents such as rituximab within 6 months prior to riliprubart dosing, or until return of B-cells counts to normal levels, whichever is longer
* Use of any specific complement system inhibitor (eg, eculizumab) within 12 weeks or 5 times the halflife of the product, whichever is longer, prior to Screening
* Treatment within 6 months prior to dosing with immunosuppressive/ chemotherapeutic medications, such as cyclophosphamide, methotrexate, tacrolimus, interferon, or tumor necrosis factor (TNF)α inhibitors. Certain immunosuppressants commonly used in CIDP (azathioprine, cyclosporine, or mycophenolate mofetil) are allowed, as indicated under inclusion criterion.
* Any vaccination received within 28 days prior to dosing (with few exceptions to be confirmed at screening)
* Participation in another clinical trial with an investigational drug or receipt of an investigational product within 12 weeks or 5 times the halflife of the product, whichever is longer, prior to Screening
* Any screening laboratory values outside normal limits or abnormal ECG considered in the Investigator's judgment to be clinically significant in the context of this trial.
* Positive result of any of the following tests:

  * hepatitis B surface antigen (HBsAg)
  * antihepatitis B core antibodies (anti-HBc Ab) (unless anti-hepatitis B surface antibodies \[antiHBs Ab\] are also positive, indicating natural immunity)
  * antihepatitis C virus (antiHCV) antibodies
  * antihuman immunodeficiency virus 1 and 2 (antiHIV1 and antiHIV2) antibodies
* Pregnancy, defined as a positive result of a highly sensitive urine or serum pregnancy test, or lactation
* Accommodation in an institution because of regulatory or legal order; eg, imprisoned or legally institutionalized
* Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or potential risk for noncompliance to study procedures
* Participants are employees at the clinical study site or other individuals directly involved in the conduct of the study, or immediate family member of such individuals
* Any country related specific regulation that would prevent the participant from entering the study
* Treatment with efgartigimod within 8 weeks prior to screening

Primary outcomes:
measure: Percentage of participants experiencing a response
timeFrame: Baseline to week 24
measure: Percentage of participants randomized to riliprubart with lasting response
timeFrame: Baseline to week 48
measure: Percentage of participants randomized to placebo who experience a response
timeFrame: Week 24 to week 48
Secondary outcomes:
measure: Change from baseline in Inflammatory Raschbuilt Overall Disability Scale (IRODS) score
timeFrame: Baseline to week 24
measure: Change from baseline in adjusted inflammatory neuropathy cause and treatment (INCAT) disability score
timeFrame: Baseline to week 24
measure: Change from baseline in grip strength (kilopascals; dominant hand)
timeFrame: Baseline to week 24
measure: Change from baseline in Medical Research Council Sum Score (MRC-SS)
timeFrame: Baseline to week 24
measure: Percentage of participants refractory to immunoglobulins experiencing a response
timeFrame: Baseline to week 24
measure: Change from baseline in the EuroQol 5 Dimension, 5-Level Health Scale (EQ-5D-5L)
timeFrame: Baseline to week 24
measure: Change from baseline in the Rasch-built modified fatigue severity scale (RT-FSS)
timeFrame: Baseline to week 24
measure: Number of participants with treatment emergent adverse events (TEAEs), including serious adverse events (SAEs) and adverse events of special interest (AESIs) for Part A
timeFrame: Baseline to week 24
measure: Incidence and titer of anti-riliprubart antibodies (ADA)
timeFrame: Baseline to week 24
measure: Number of participants with TEAEs, including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) for Part B
timeFrame: Week 24 to week 111
measure: Incidence and titer of anti-riliprubart antibodies
timeFrame: Week 24 to week 111
measure: Change from baseline in I RODS score
timeFrame: Baseline to week 48
measure: Change from baseline in adjusted INCAT score
timeFrame: Baseline to week 48
measure: Change from baseline in grip strength (kilopascals; dominant hand)
timeFrame: Baseline to week 48
measure: Change from baseline in MRC-SS
timeFrame: Baseline to week 48
measure: Change from baseline in EQ-5D-5L score
timeFrame: Baseline to week 48
measure: Change from baseline in RT-FSS
timeFrame: Baseline to week 48
measure: Percentage of participants randomized to riliprubart who experience a response at Week 48 without prior response in Part A (delayed response)
timeFrame: Baseline to week 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Neurology Associates- Site Number : 8400019
state: Alabama
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center- Site Number : 8400002
state: California
city: Orange
country: United States
facility: University of California Irvine - Manchester Pavilion- Site Number : 8400007
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine- Site Number : 8400018
state: Connecticut
city: Glenview
country: United States
facility: Northshore Medical Group- Site Number : 8400024
state: Illinois
city: Westwood
country: United States
facility: The University of Kansas Cancer Center - Westwood- Site Number : 8400010
state: Kansas
city: Alexandria
country: United States
facility: NeuroMedical Clinic of Central Louisiana- Site Number : 8400031
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Medical Center - Jefferson Highway- Site Number : 8400030
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital- Site Number : 8400015
state: Maryland
city: Boston
country: United States
facility: ~Mass General Hospital- Site Number : 8400009
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital- Site Number : 8400025
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center- Site Number : 8400037
state: Missouri
city: New York
country: United States
facility: Columbia University Irving Medical Center- Site Number : 8400003
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati - Internal Medicine- Site Number : 8400020
state: Ohio
city: Philadelphia
country: United States
facility: Penn Medicine: University of Pennsylvania Health System- Site Number : 8400022
state: Pennsylvania
city: Burlington
country: United States
facility: University of Vermont Medical Center- Site Number : 8400012
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia- Site Number : 8400023
state: Virginia
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320001
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320002
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320003
city: Leuven
country: Belgium
facility: Investigational Site Number : 0560001
city: Salvador
country: Brazil
facility: Hospital Sao Rafael- Site Number : 0760011
state: Bahia
city: Vitoria
country: Brazil
facility: Centro de Diagnostico e Pesquisa da Osteoporose do Espirito Santo- Site Number : 0760012
state: Espírito Santo
city: Porto Alegre
country: Brazil
facility: Hospital Moinhos de Vento- Site Number : 0760003
state: Rio Grande Do Sul
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto- Site Number : 0760007
state: São Paulo
city: São Paulo
country: Brazil
facility: PSEG Centro de Pesquisa Clínica- Site Number : 0760009
city: Blagoevgrad
country: Bulgaria
facility: Investigational Site Number : 1000002
city: Pleven
country: Bulgaria
facility: Investigational Site Number : 1000001
city: Quebec
country: Canada
facility: Investigational Site Number : 1240001
city: Santiago
country: Chile
facility: Investigational Site Number : 1520003
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520002
state: Reg Metropolitana De Santiago
city: Santiago
country: Chile
facility: Investigational Site Number : 1520001
state: Reg Metropolitana De Santiago
city: Beijing
country: China
facility: Investigational Site Number : 1560013
city: Beijing
country: China
facility: Investigational Site Number : 1560010
city: Beijing
country: China
facility: Investigational Site Number : 1560005
city: Changsha
country: China
facility: Investigational Site Number : 1560009
city: Chengdu
country: China
facility: Investigational Site Number : 1560011
city: Fuzhou
country: China
facility: Investigational Site Number : 1560002
city: Guangzhou
country: China
facility: Investigational Site Number : 1560012
city: Guangzhou
country: China
facility: Investigational Site Number : 1560007
city: Hangzhou
country: China
facility: Investigational Site Number : 1560014
city: Jinan
country: China
facility: Investigational Site Number : 1560008
city: Nanchang
country: China
facility: Investigational Site Number : 1560015
city: Shanghai
country: China
facility: Investigational Site Number : 1560001
city: Wuhan
country: China
facility: Investigational Site Number : 1560003
city: Wuhan
country: China
facility: Investigational Site Number : 1560006
city: Xi'an
country: China
facility: Investigational Site Number : 1560004
city: Brno
country: Czechia
facility: Investigational Site Number : 2030004
city: Hradec Králové
country: Czechia
facility: Investigational Site Number : 2030003
city: Pardubice
country: Czechia
facility: Investigational Site Number : 2030002
city: Aarhus
country: Denmark
facility: Investigational Site Number : 2080002
city: Copenhagen
country: Denmark
facility: Investigational Site Number : 2080001
city: Le Kremlin-bicêtre
country: France
facility: Investigational Site Number : 2500001
city: Marseille
country: France
facility: Investigational Site Number : 2500002
city: Montpellier
country: France
facility: Investigational Site Number : 2500005
city: Paris
country: France
facility: Investigational Site Number : 2500004
city: Bad Homburg
country: Germany
facility: Investigational Site Number : 2760001
city: Athens
country: Greece
facility: Investigational Site Number : 3000002
city: Thessaloniki
country: Greece
facility: Investigational Site Number : 3000001
city: Milan
country: Italy
facility: Investigational Site Number : 3800001
state: Milano
city: Rozzano
country: Italy
facility: Investigational Site Number : 3800009
state: Milano
city: Rome
country: Italy
facility: Investigational Site Number : 3800006
state: Roma
city: Rome
country: Italy
facility: Investigational Site Number : 3800002
state: Roma
city: Rome
country: Italy
facility: Investigational Site Number : 3800008
state: Roma
city: Messina
country: Italy
facility: Investigational Site Number : 3800007
city: Palermo
country: Italy
facility: Investigational Site Number : 3800003
city: Pavia
country: Italy
facility: Investigational Site Number : 3800005
city: Pisa
country: Italy
facility: Investigational Site Number : 3800004
city: Roma
country: Italy
facility: Investigational Site Number : 3800002
city: Osakasayama
country: Japan
facility: Investigational Site Number : 3920006
state: Osaka
city: Kawagoe
country: Japan
facility: Investigational Site Number : 3920005
state: Saitama
city: Bunkyo
country: Japan
facility: Investigational Site Number : 3920011
state: Tokyo
city: Kodaira
country: Japan
facility: Investigational Site Number : 3920008
state: Tokyo
city: Chiba
country: Japan
facility: Investigational Site Number : 3920001
city: Fukuoka
country: Japan
facility: Investigational Site Number : 3920003
city: Saga
country: Japan
facility: Investigational Site Number : 3920009
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100003
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100002
state: Seoul-teukbyeolsi
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number : 4100001
state: Seoul-teukbyeolsi
city: Guadalajara
country: Mexico
facility: Investigational Site Number : 4840003
state: Jalisco
city: Culiacan
country: Mexico
facility: Investigational Site Number : 4840005
state: Sinaloa
city: Veracruz
country: Mexico
facility: Investigational Site Number : 4840002
city: Rotterdam
country: Netherlands
facility: Investigational Site Number : 5280002
city: Lublin
country: Poland
facility: Investigational Site Number : 6160002
state: Lubelskie
city: Krakow
country: Poland
facility: Investigational Site Number : 6160006
state: Malopolskie
city: Rzeszow
country: Poland
facility: Investigational Site Number : 6160003
state: Podkarpackie
city: Lisbon
country: Portugal
facility: Investigational Site Number : 6200004
city: Lisbon
country: Portugal
facility: Investigational Site Number : 6200001
city: Matosinhos
country: Portugal
facility: Investigational Site Number : 6200003
city: Oviedo
country: Spain
facility: Investigational Site Number : 7240005
state: Asturias
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240008
state: Barcelona [Barcelona]
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240001
state: Catalunya [Cataluña]
city: Majadahonda
country: Spain
facility: Investigational Site Number : 7240006
state: Madrid
city: Pamplona
country: Spain
facility: Investigational Site Number : 7240003
state: Navarra
city: Bilbao
country: Spain
facility: Investigational Site Number : 7240007
state: Pais Vasco
city: Valencia
country: Spain
facility: Investigational Site Number : 7240002
city: Stockholm
country: Sweden
facility: Investigational Site Number : 7520001
city: Kaohsiung City
country: Taiwan
facility: Investigational Site Number : 1580003
city: Taipei City
country: Taiwan
facility: Investigational Site Number : 1580001
city: Bursa
country: Turkey
facility: Investigational Site Number : 7920002
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920001
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920004
city: Konya
country: Turkey
facility: Investigational Site Number : 7920003
Study officials:
References: