Resumen

El propósito del estudio es evaluar la eficacia de riliprubart en comparación con placebo en participantes adultos con CIDP cuya enfermedad es refractaria al tratamiento estándar. La duración del estudio será de un máximo de 111 semanas, incluyendo las fases de selección, tratamiento y seguimiento.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

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
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Intervenciones

drug

Riliprubart

Pharmaceutical form: Solution Route of administration: IV Infusion

drug

Placebo

Pharmaceutical form: Solution Route of administration: IV Infusion

drug

Riliprubart

Pharmaceutical form: Solution Route of administration: SC Injection

drug

Placebo

Pharmaceutical form: Solution Route of administration: SC Injection

Estudio de Fase 3, doble ciego, controlado con placebo para evaluar la eficacia y seguridad de riliprubart en participantes con Polineuropatía Desmielinizante Inflamatoria Crónica refractaria

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Riliprubart

Placebo

Riliprubart

Placebo

Ubicaciones

Investigational Site Number : 0320001

Investigational Site Number : 0320002

Investigational Site Number : 0320003

Patrocinadores

Contactos

Trial Transparency email recommended (Toll free for US & Canada)