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A Phase 3, double-blind, placebo-controlled study evaluating efficacy and safety of riliprubart in participants with refractory chronic inflammatory demyelinating polyneuropathy

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 (MOBILIZE)

Obara Kentaro

Sanofi K.K.

Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan

clinical-trials-jp@sanofi.com

Clinical Study Unit

Sanofi K.K.

Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo 163-1488, Japan

+81-3-6301-3670

clinical-trials-jp@sanofi.com

Recruiting

July. 11, 2024

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

Participants are eligible to be included in the study only if all of the following criteria apply:
- Participant must have chronic inflammatory demyelinating polyneuropathy (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
- - Immunoglobulin-refractory subgroup: Historic evidence of failure or inadequate response to immunoglobulin therapy prior to screening, defined as no clinically meaningful improvement or persistent inflammatory neuropathy cause and treatment (INCAT) score >=2 after a minimum of:
- - - One dose of intravenous immunoglobulin (IVIg) of 2 g/kg, followed by either a second dose of 2 g/kg or at least 2 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
- - - Subcutaneous immunoglobulin (SCIg) maintenance therapy with at least 0.2 g/kg weekly for 5 weeks
- - Corticosteroid-refractory 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 intravenous (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 Inflammatory rasch-built overall disability scale (I-RODS) centile score >=4 points
- - - An increase in Medical Research Council (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 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 (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 the protocol 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
- A body weight at Screening of 35 kg to 154 kg (77 to 340 lbs), inclusive

Participants are excluded from the study if any of the following criteria apply:
- Polyneuropathy of other causes, including but not limited to: acute demyelinating polyneuropathies (eg, Guillain-Barre syndrome), 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, polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (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 (hemoglobin A1c [HbA1c] >7% at the Screening visit)
- 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 benefit-risk 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 Columbia Suicide Severity Rating Scale (C-SSRS) 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 12 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-cell counts to normal levels, whichever is longer
- Use of any specific complement system inhibitor (eg, eculizumab) within 12 weeks or 5 times the half-life 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)-alpha 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 half-life of the product, whichever is longer, prior to Screening
- Any screening laboratory values outside normal limits or abnormal electrocardiogram 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)
- - anti-hepatitis B core antibodies (anti-HBc Ab) (unless anti-hepatitis B surface antibodies [anti-HBs Ab] are also positive, indicating natural immunity)
- - anti-hepatitis C virus (anti-HCV) antibodies
- - anti-human immunodeficiency virus 1 and 2 (anti-HIV1 and anti-HIV2) 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

Both

chronic inflammatory demyelinating polyneuropathy

Drug: Riliprubart (SAR445088)
Pharmaceutical form: Solution, Route of administration: intravenous (IV) Infusion
Drug: Placebo
Pharmaceutical form: Solution, Route of administration: IV Infusion
Drug: Riliprubart (SAR445088)
Pharmaceutical form: Solution, Route of administration: subcutaneous (SC) Injection
Drug: Placebo
Pharmaceutical form: Solution, Route of administration: SC Injection

Arm description:
- Experimental: Riliprubart Arm
Riliprubart for 24 weeks followed by open-label extension phase with riliprubart for 24 weeks
- Placebo Comparator: Placebo Arm
Placebo for 24 weeks followed by open-label extension phase with riliprubart for 24 weeks

1. Percentage of participants experiencing a response
[Time Frame: Baseline to Week 24]
A response is defined as a decrease of >=1 point from baseline in adjusted inflammatory neuropathy cause and treatment (INCAT) disability score at Week 24.
2. Percentage of participants randomized to riliprubart with lasting response
[Time Frame: Baseline to Week 48]
Lasting response is defined as a decrease of >= 1 point in adjusted INCAT disability score at week 48 versus baseline.
3. Percentage of participants randomized to placebo who experience a response
[Time Frame: Week 24 to Week 48]
A response is defined as a decrease of >=1 point in adjusted INCAT disability score at Week 48 versus week 24.

1. Change from baseline in Inflammatory Rasch-built Overall Disability Scale (I-RODS) score
[Time Frame: Baseline to Week 24]
2. Change from baseline in adjusted INCAT disability score
[Time Frame: Baseline to Week 24]
3. Change from baseline in grip strength (kilopascals; dominant hand)
[Time Frame: Baseline to Week 24]
4. Change from baseline in Medical Research Council Sum Score (MRC-SS)
[Time Frame: Baseline to Week 24]
5. Percentage of participants refractory to immunoglobulins experiencing a response
[Time Frame: Baseline to Week 24]
A response is defined as a decrease of >=1 point from baseline in adjusted INCAT disability score at Week 24
6. Change from baseline in the EuroQol 5 Dimension, 5-Level Health Scale (EQ-5D-5L)
[Time Frame: Baseline to Week 24]
7. Change from baseline in the Rasch-built modified fatigue severity scale (RT-FSS)
[Time Frame: Baseline to Week 24]
8. Number of participants with treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) and adverse events of special interest (AESIs) for Part A
[Time Frame: Baseline to Week 24]
9. Incidence and titer of anti-riliprubart antibodies (ADA)
[Time Frame: Baseline to Week 24]
10. Number of participants with TEAEs, including SAEs and AESIs for Part B
[Time Frame: Week 24 to Week 111]
11. Incidence and titer of ADA
[Time Frame: Week 24 to Week 111]
12. Change from baseline in I-RODS score
[Time Frame: Baseline to Week 48]
13. Change from baseline in adjusted INCAT disability score
[Time Frame: Baseline to Week 48]
14. Change from baseline in grip strength (kilopascals; dominant hand)
[Time Frame: Baseline to Week 48]
15. Change from baseline in MRC-SS
[Time Frame: Baseline to Week 48]
16. Percentage of participants randomized to riliprubart who experience a response at Week 48 without prior response in Part A (delayed response)
[Time Frame: Baseline to week 48]
A delayed response is defined as a decrease of >=1 point in adjusted INCAT disability score at Week 48 versus baseline
17. Change from baseline in EQ-5D-5L score
[Time Frame: Baseline to Week 48]
18. Change from baseline in RT-FSS
[Time Frame: Baseline to Week 48]

June. 17, 2024

Yes

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

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