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A Phase 3, randomized, double-blind, study evaluating efficacy and safety of riliprubart versus intravenous immunoglobulin (IVIg) in participants with chronic inflammatory demyelinating polyneuropathy

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)

Obara Kentaro

Sanofi K.K.

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

clinical-trials-jp@sanofi.com

Clinical Study Unit

Sanofi K.K.

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

+81-3-6301-3670

clinical-trials-jp@sanofi.com

Recruiting

Sept. 30, 2024

Interventional

randomized controlled trial

double blind

active 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 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 (including motor-predominant 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 Inflammatory Neuropathy Cause and Treatment (INCAT) score, >=4 points increase in Inflammatory Rasch-built Overall Disability Scale (I-RODS) centile score, >=3 points increase in the Medical research council sum score (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. The IVIg maintenance dosing regimen should be equivalent or higher than a weekly dose of 0.1 g/kg body weight (for example, 0.3 g/kg every 3 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) 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.
- 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 (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), 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.
- 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.

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, monoclonal plasma cell disorder, skin changes (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 (HbA1c [glycated hemoglobin] >7% at the Screening visit).
- 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) 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 immunoglobulin A (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 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.
- 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 until return of B-cell counts 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 electrocardiogram (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.
- - 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.
- 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: Riliprubart placebo
Pharmaceutical form: Solution, Route of administration: IV infusion
Drug: riliprubart (SAR445088)
Pharmaceutical form: Solution, Route of administration: subcutaneous (SC) injection
Drug: Riliprubart placebo
Pharmaceutical form: Solution, Route of administration: SC injection
Drug: IVIg
Pharmaceutical form: Concentrate for solution for infusion (or any other formulation approved locally), Route of administration: IV infusion
Drug: IVIg Placebo
Pharmaceutical form: Placebo to match IVIg for IV infusion, Route of administration: IV infusion
Drug: IVIg premedication
Pharmaceutical form: Per respective labels, Route of administration: Per respective labels

Study Arms:
Experimental: Riliprubart Arm
- Riliprubart + Placebo IVIg for 24 weeks followed by open-label extension phase with riliprubart for 24 weeks
- - Interventions: Riliprubart, IVIg placebo, IVIg premedication
Active Comparator: IVIg Arm
- IVIg (IVIg continuation) + Placebo riliprubart for 24 weeks followed by open-label extension phase with riliprubart for 24 weeks
- - Interventions: Riliprubart placebo, riliprubart, IVIg, IVIg premedication

1. Percentage of participants experiencing a response
[Time Frame: Baseline to week 24]
A response is defined as decrease of >=1 point from baseline in adjusted INCAT disability score at Week 24.
2. Percentage of participants randomized to riliprubart who responded during part A and had a lasting response during the open-label treatment extension period
[Time Frame: Baseline to week 48]
Lasting response is defined as a decrease of >=1 point in adjusted INCAT disability score.

1. Change from baseline in 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 MRC-SS
[Time Frame: Baseline to week 24]
5. Change from baseline in the Rasch-built modified fatigue severity scale (RT-FSS)
[Time Frame: Baseline to week 24]
6. Percentage of participants experiencing a relapse
[Time Frame: Baseline to week 24]
A relapse is defined as increase of >=1 point from baseline in adjusted INCAT disability score.
7. Change from baseline in the EuroQol 5 Dimension, 5-Level Health Scale (EQ-5D-5L)
[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 of treatment-emergent antidrug antibodies (ADA) in participants treated with riliprubart
[Time Frame: Baseline to week 24]
10. Number of participants with TEAEs, including SAEs and AESIs
[Time Frame: Week 24 to week 48]
11. Incidence and titer of anti-drug antibodies (ADA) during open-label treatment and follow-up
[Time Frame: Baseline to week 109]
12. Change from baseline in I-RODS
[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. Change from baseline in EQ-5D-5L score
[Time Frame: Baseline to week 48]
17. Percentage of participants randomized to IVIg continuation who experienced a response
[Time Frame: Week 24 to week 48]
A response is defined as a decrease of >= 1 point in adjusted INCAT disability scale score at Week 48 versus Week 24
18. Percentage of participants randomized to riliprubart who experienced 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
19. Percentage of participants randomized to riliprubart experiencing a relapse
[Time Frame: Baseline to week 48]
A relapse is defined as an increase of >= 1 point from baseline in adjusted INCAT disability score at Week 48 versus Baseline
20. Percentage of participants randomized to riliprubart experiencing a relapse
[Time Frame: Week 24 to week 48]
A relapse is defined as an increase of >= 1 point from baseline in adjusted INCAT disability score at Week 48 versus Week 24
21. Change from baseline in RT-FSS
[Time Frame: Baseline to week 48]

July. 22, 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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