A Study to Test the Efficacy and Safety of Riliprubart Against the Usual Treatment of Intravenous Immunoglobulin (IVIg) in People With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (VITALIZE)

Sanofi

Status and phase: Enrolling; Phase 3

Conditions: Chronic Inflammatory Demyelinating Polyneuropathy

Treatments: Drug: IVIg; Drug: Placebo; Drug: riliprubart

Study type: Interventional

Funder types: Industry

Identifiers

NCT06290141

2023-508338-33 (Registry Identifier)

EFC18156

U1111-1295-3363 (Registry Identifier)

Details and patient eligibility

About

The purpose of the study is to evaluate efficacy of riliprubart compared to IVIg in adult participants with CIDP who are receiving maintenance treatment with IVIg. The study duration will be for a maximum of 109 weeks including screening, treatment phases, and follow-up.

Enrollment: 160 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 2 CIDP variants: motor CIDP, multifocal CIDP (also known as Lewis Sumner Syndrome). Diagnosis must be confirmed by the study adjudication committee.
• Participants must have responded to IVIg in the past 5 years.
• Participant must be on a stable maintenance dosage of IVIg.
• Participant must have residual disability, defined as an INCAT score of 2 to 9 at Screening that is confirmed at baseline (a score of 2 should be exclusively from leg disability component of INCAT).
• Participant must be receiving treatment with IVIg within a standard maintenance dosing regimen, defined as per EAN/PNS 2021 CIDP guidelines.
• Participants receiving IVIg infusions at home are eligible, as long as IVIg infusions are switched to a hospital or infusion center setting at least 1 cycle prior to baseline.
• 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.
• Contraception for sexually active male or female participants; not pregnant or breastfeeding; no sperm donating for male participant
• Participant must have a body weight at Screening of 35 kg to 154 kg (77 to 340 lbs) inclusive.
• Evidence of at least one clinically meaningful deterioration within 2 years, or at least 2 clinically meaningful deteriorations within 5 years prior to screening which occurred during period of interrupted dosing, reduced dosage, or extended intervals between doses of immunoglobin therapy, as verified by clinical examination or medical records.

Exclusion criteria

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-Barré syndrome), hereditary demyelinating neuropathies, neuropathies secondary to infection or systemic disease, diabetic neuropathy, drug- or toxin-induced neuropathies, multifocal motor neuropathy, polyneuropathy related to IgM monoclonal gammopathy, POEMS syndrome, 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

• Serious infections requiring hospitalization within 30 days prior to Screening, any active infection requiring antimicrobial 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 contraindication related to the administration of immunoglobulins (eg hypersensitivity, chronic kidney disease, thromboembolic diseases or recent thromboembolic event, known history of IgA deficiency at the time of Screening).

• Any other clinically meaningful medical history or ongoing medical condition (as determined by the Investigator at Screening) that might impact the 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 the 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 the 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.

• Recent treatment with plasma exchange

• Treatment within 3 months prior to dosing with immunosuppressive/ immunomodulator medication, or corticosteroids (with exception of maintenance dose, which is allowed), or prior treatment (at any time) with highly immunosuppressive/ chemotherapeutic medications with sustained effects (eg, mitoxantrone, alemtuzumab, or cladribine).

• Prior treatment with riliprubart.

• Recent use of any specific complement system inhibitor (eg, eculizumab).

• 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.

• 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 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).
  • 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. Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis RNA test is obtained.
  • 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; imprisoned or legally institutionalized.

• Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.

• Participants are employees of the clinical study site or other individuals directly involved in the conduct of the study, or immediate family members of such individuals.

• Any country-related specific regulation that would prevent the participant from entering the study as defined by the protocol.

• Recent treatment with efgartigimod.

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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160 participants in 2 patient groups

Riliprubart Arm

Experimental group

Description:

Riliprubart + Placebo IVIg for 24 weeks followed by open-label extension phase with riliprubart for 24 weeks

Treatment:

Drug: Placebo

Drug: riliprubart

Drug: riliprubart

Drug: Placebo

Drug: Placebo

IVIg Arm

Active Comparator group

Description:

IVIg (IVIg continuation) + Placebo riliprubart for 24 weeks followed by open-label extension phase with riliprubart for 24 weeks

Treatment:

Drug: Placebo

Drug: riliprubart

Drug: riliprubart

Drug: Placebo

Drug: IVIg

Drug: Placebo