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)

Chronic Inflammatory Demyelinating Polyneuropathy Clinical Trial

— VITALIZE  

Official title:

A Phase 3, Randomized, Double-blind, Study Evaluating Efficacy and Safety of Riliprubart Versus Intravenous Immunoglobulin (IVIg) in Participants With Chronic Inflammatory Demyelinating Polyneuropathy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06290141
• Other study ID #: EFC18156
• Secondary ID: U1111-1295-33632
• Status: Recruiting
• Phase: Phase 3
• Start date: May 31, 2024
• Est. completion date: May 19, 2027

Study information

• Verified date: April 2024
• Source: Sanofi
• Contact: Trial Transparency email recommended (Toll free for US & Canada)
• Phone: 800-633-1610
• Email: Contact-US[@]sanofi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 160
• Est. completion date: May 19, 2027
• Est. primary completion date: November 5, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)/ Peripherial 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. Response must be an objective clinically meaningful improvement defined by at least one of the following: =1 point decrease in adjusted INCAT score, =4 points increase in I-RODS total score, =3 points increase in the MRC-SS, =8 kilopascal improvement in mean grip strength (1 hand), or an equivalent improvement based on information documented in medical records as per the Investigator's judgment.

• Participant must be on a stable maintenance dosage of IVIg, defined as no change greater than 10% in frequency or dose of IVIg within 8 weeks prior to Screening, and remaining stable until baseline.

• 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: 0.4 to 1 g/kg every 2 to 6 weeks.

• 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) XE " CDAS " \f Abbreviation \t "CIDP disease activity score" of =2 points at Screening.

• Participant must have documented vaccinations against encapsulated bacterial pathogens given within 5 years of Screening 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.

• A male participant is 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, either:

--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 (Contraceptive and barrier guidance per protocol) when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant.

• 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 WOCBP and agrees to use a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, 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.

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 IgM monoclonal gammopathy, POEMS XE " POEMS " \f Abbreviation \t "polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes" 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 (HbA1c XE " HbA1c " \f Abbreviation \t "glycated hemoglobin" >7%).

• Serious infections requiring hospitalization within 30 days prior to Screening, 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)

• 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 XE " IgA " \f Abbreviation \t "immunoglobulin A" 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 XE " C-SSRS " \f Abbreviation \t "Coiumbia-Suicide Severity Rating Scale" 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.

• Treatment with plasma exchange within 8 weeks prior to Screening.

• Treatment within 3 months prior to dosing with immunosuppressive/ immunomodulator medication, or corticosteroids (except =20 mg/day of prednisone or equivalent 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.

• 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.

• 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 before B-cell counts return to normal levels, whichever is longer.

• 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:

• HBsAg XE " HBsAg " \f Abbreviation \t "Hepatitis B surface antigen" .

• Anti-HBc Ab XE " HBc Ab " \f Abbreviation \t "Hepatitis B core antibodies" ; unless anti-HBs Ab XE " HBs Ab " \f Abbreviation \t "Hepatitis B surface antibody" are also positive, indicating natural immunity.

• Anti-HCV XE " HCV " \f Abbreviation \t "Hepatitis C virus" antibodies.

• Anti-HIV1 XE " HIV1" \f Abbreviation \t "human immunodeficiency virus 1" and anti-HIV2 XE " HIV2" \f Abbreviation \t "human immunodeficiency virus 2" 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 XE " ICH " \f Abbreviation \t "Internation Council of Harmonization" XE " GCP " \f Abbreviation \t "Good clinical practice" .

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• riliprubart
Pharmaceutical form:Solution-Route of administration:IV solution
• Placebo
Pharmaceutical form:Solution-Route of administration:IV solution
• riliprubart
Pharmaceutical form:Solution-Route of administration:SC solution
• Placebo
Pharmaceutical form:Solution-Route of administration:SC solution
• IVIg
Pharmaceutical form:Concentrate for solution for infusion (or any other formulation approved locally)-Route of administration:IV solution
• Placebo
Pharmaceutical form:Placebo to match intravenous immunoglobulin IVIg for IV infusion-Route of administration:IV solution
• IVIg premedication
Pharmaceutical form:Per respective labels-Route of administration:Per respective labels

Locations

Country	Name	City	State
United States	Alabama Neurology Associates Site Number : 8400019	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants experiencing a response	A response is defined as decrease of =1 point from baseline in adjusted INCAT disability score at Week 24	Baseline to week 24
Primary	Percentage of participants randomized to riliprubart who responded during the double-blind period and had a lasting response during the open-label period	Lasting response is defined as a decrease of =1 point no in adjusted INCAT disability score	Baseline to week 48
Secondary	Change from baseline in Rasch-built Overall Disability Scale (I-RODS) score		Baseline to week 24
Secondary	Change from baseline in adjusted inflammatory neuropathy cause and treatment (INCAT) disability score		Baseline to week 24
Secondary	Change from baseline in grip strength (kilopascals, dominant hand)		Baseline to week 24
Secondary	Change from baseline in Medical Research Council Sum Score (MRC-SS)		Baseline to week 24
Secondary	Change from baseline in the Rasch-built modified fatigue severity scale (RT-FSS)		Baseline to week 24
Secondary	Percentage of participants experiencing a relapse	A relapse is defined as increase of =1 point from baseline in adjusted INCAT disability score	Baseline to week 24
Secondary	Change from baseline in the EuroQol 5 Dimension, 5-Level Health Scale (EQ-5D-5L)		Baseline to week 24
Secondary	Number of participants with TEAEs, including SAEs and AESIs		Baseline to week 24
Secondary	Number of participants with treatment-emergent ADA in participants treated with riliprubart		Baseline to week 24
Secondary	Number of participants with TEAEs, including SAEs and AESIs		Week 24 to week 48
Secondary	Percentage of participants randomized to riliprubart experiencing a relapse	A relapse is defined as an increase of =1 point from baseline	Week 24 to week 48
Secondary	Percentage of participants randomized to IVIg continuation experiencing a relapse	A relapse is defined as an increase of =1 point from baseline in adjusted INCAT disability score	Week 24 to week 48
Secondary	Number of participants and titer of anti-drug antibodies (ADA)		Baseline to week 109
Secondary	Change from baseline in I-RODS		Baseline to week 48
Secondary	Change from baseline in adjusted INCAT score		Baseline to week 48
Secondary	Change from baseline in grip strength (kilopascals; dominant hand)		Baseline to week 48
Secondary	Change from baseline in MRC-SS		Baseline to week 48
Secondary	Change from baseline in RT-FSS		Baseline to week 48
Secondary	Change from baseline in EQ-5D-5L score		Baseline to week 48
Secondary	Percentage of participants randomized to riliprubart who experience a response during the open-label period without prior response in the double-blind period (delayed response)	A delayed response is defined as a decrease of =1 point in adjusted INCAT disability score	Week 24 to week 48
Secondary	Percentage of participants randomized to IVIg continuation who experience a response	A response is defined as a decrease of =1 point in adjusted INCAT disability score	Week 24 to week 48