Clinical trial NCT06290141: 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)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Inflammatory Demyelinating Polyneuropathy
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2024-03-04
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part A is a double-blind treatment period and Part B is an open-label period.
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

1. 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).
2. 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.
3. 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 centile 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.
4. 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.
5. 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).
6. 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).
7. 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.
8. Participant must have active disease, defined by a CIDP disease activity score (CDAS) of ≥2 points at Screening.
9. 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.
10. All participants must agree to use contraception methods during and after the study as required.
11. 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.
12. 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:
13. 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.
14. 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.
15. Participant must have a body weight at Screening of 35 kg to 154 kg (77 to 340 lbs) inclusive.
16. 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:

1. 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.
2. Sensory CIDP, distal CIDP and focal CIDP variants.
3. Any other neurological or systemic disease that can cause symptoms and signs interfering with treatment or outcome assessments.
4. Poorly controlled diabetes (HbA1c glycated hemoglobin \>7% at the Screening visit).
5. 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).
6. 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.
7. 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.
8. 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).
9. 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.
10. 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.
11. Evidence of CIDP worsening within the 6 weeks following a prior vaccination that, in the opinion of the Investigator, constituted a relapse.
12. Recent or planned major surgery that could confound the results of the trial or put the participant at undue risk.
13. Treatment with plasma exchange within 8 weeks prior to Screening.
14. 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).
15. Prior treatment with riliprubart.
16. 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.
17. Prior treatment (any time) with total lymphoid irradiation or bone marrow transplantation.
18. 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.
19. Any vaccination received within 28 days prior to dosing (with few exceptions to be confirmed at screening).
20. 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.
21. 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.
22. Positive result of any of the following tests:

    * HBsAg
    * Anti-HBc; unless anti-HBs Ab X are also positive, indicating natural immunity.
    * Anti-HCV antibodies.
    * Anti-HIV1 and anti-HIV2 antibodies.
23. Pregnancy, defined as a positive result of a highly sensitive urine or serum pregnancy test, or lactation.
24. Accommodation in an institution because of regulatory or legal order; imprisoned or legally institutionalized.
25. 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.
26. 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.
27. Any country-related specific regulation that would prevent the participant from entering the study as defined by the protocol.
28. Treatment with efgartigimod within 8 weeks prior to screening.

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

Primary outcomes:
measure: Percentage of participants experiencing a response
timeFrame: Baseline to week 24
measure: Percentage of participants randomized to riliprubart who responded during part A and had a lasting response during the open-label treatment extension period
timeFrame: Baseline to week 48
Secondary outcomes:
measure: Change from baseline in Rasch-built Overall Disability Scale (I-RODS) score
timeFrame: Baseline to week 24
measure: Change from baseline in adjusted inflammatory neuropathy cause and treatment (INCAT) disability score
timeFrame: Baseline to week 24
measure: Change from baseline in grip strength (kilopascals, dominant hand)
timeFrame: Baseline to week 24
measure: Change from baseline in Medical Research Council Sum Score (MRC-SS)
timeFrame: Baseline to week 24
measure: Change from baseline in the Rasch-built modified fatigue severity scale (RT-FSS)
timeFrame: Baseline to week 24
measure: Percentage of participants experiencing a relapse
timeFrame: Baseline to week 24
measure: Change from baseline in the EuroQol 5 Dimension, 5-Level Health Scale (EQ-5D-5L)
timeFrame: Baseline to week 24
measure: Number of participants with TEAEs, including SAEs and AESIs for Part A
timeFrame: Baseline to week 24
measure: Number of participants with treatment-emergent ADA in participants treated with riliprubart
timeFrame: Baseline to week 24
measure: Number of participants with TEAEs, including SAEs and AESIs
timeFrame: Week 24 to week 48
measure: Incidence and titer of anti-drug antibodies (ADA) during open-label treatment and follow-up
timeFrame: Baseline to week 109
measure: Change from baseline in I-RODS
timeFrame: Baseline to week 48
measure: Change from baseline in adjusted INCAT score
timeFrame: Baseline to week 48
measure: Change from baseline in grip strength (kilopascals; dominant hand)
timeFrame: Baseline to week 48
measure: Change from baseline in MRC-SS
timeFrame: Baseline to week 48
measure: Change from baseline in EQ-5D-5L score
timeFrame: Baseline to week 48
measure: Percentage of participants randomized to IVIg continuation who experienced a response
timeFrame: Week 24 to week 48
measure: Percentage of participants randomized to riliprubart who experienced a response at Week 48 without prior response in Part A (delayed response)
timeFrame: Baseline to Week 48
measure: Percentage of participants randomized to riliprubart experiencing a relapse
timeFrame: Baseline to week 48
measure: Change from baseline in RT-FSS
timeFrame: Baseline to week 48
measure: Percentage of participants randomized to riliprubart experiencing a relapse
timeFrame: Week 24 to week 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Neurology Associates- Site Number : 8400019
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Neurological Associates - Phoenix- Site Number : 8400014
state: Arizona
city: Los Angeles
country: United States
facility: Keck School of Medicine of University of Southern California- Site Number : 8400002
state: California
city: Orange
country: United States
facility: University of California Irvine Medical Center- Site Number : 8400007
state: California
city: Orlando
country: United States
facility: AdventHealth Orlando- Site Number : 8400006
state: Florida
city: Orlando
country: United States
facility: AdventHealth Site Number : 8400006
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center- Site Number : 8400010
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Medical Center - Jefferson Highway- Site Number : 8400030
state: Louisiana
city: Boston
country: United States
facility: ~Mass General Hospital- Site Number : 8400009
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital- Site Number : 8400025
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University- Site Number : 8400038
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center- Site Number : 8400037
state: Missouri
city: Amherst
country: United States
facility: Dent Neurologic Institute - Amherst- Site Number : 8400039
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center- Site Number : 8400003
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati - Internal Medicine- Site Number : 8400020
state: Ohio
city: Charlottesville
country: United States
facility: University of Virginia- Site Number : 8400023
state: Virginia
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320001
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320002
city: Buenos Aires
country: Argentina
facility: Investigational Site Number : 0320003
city: Gent
country: Belgium
facility: Investigational Site Number : 0560002
city: Leuven
country: Belgium
facility: Investigational Site Number : 0560001
city: Brasília
country: Brazil
facility: L2IP - Instituto de Pesquisas Clínicas- Site Number : 0760006
state: Distrito Federal
city: Curitiba
country: Brazil
facility: Instituto de Neurologia de Curitiba - Ecoville- Site Number : 0760007
state: Paraná
city: Porto Alegre
country: Brazil
facility: InsCer - Instituto do Cérebro da PUCRS- Site Number : 0760002
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: PSEG Centro de Pesquisa Clínica- Site Number : 0760009
city: London
country: Canada
facility: Investigational Site Number : 1240003
state: Ontario
city: Montreal
country: Canada
facility: Investigational Site Number : 1240006
state: Quebec
city: Quebec
country: Canada
facility: Investigational Site Number : 1240001
city: Beijing
country: China
facility: Investigational Site Number : 1560013
city: Beijing
country: China
facility: Investigational Site Number : 1560010
city: Beijing
country: China
facility: Investigational Site Number : 1560005
city: Changsha
country: China
facility: Investigational Site Number : 1560009
city: Chengdu
country: China
facility: Investigational Site Number : 1560011
city: Fuzhou
country: China
facility: Investigational Site Number : 1560002
city: Guangzhou
country: China
facility: Investigational Site Number : 1560012
city: Guangzhou
country: China
facility: Investigational Site Number : 1560007
city: Hangzhou
country: China
facility: Investigational Site Number : 1560014
city: Jinan
country: China
facility: Investigational Site Number : 1560008
city: Nanchang
country: China
facility: Investigational Site Number : 1560015
city: Shanghai
country: China
facility: Investigational Site Number : 1560001
city: Wuhan
country: China
facility: Investigational Site Number : 1560003
city: Wuhan
country: China
facility: Investigational Site Number : 1560006
city: Xi'an
country: China
facility: Investigational Site Number : 1560004
city: Brno
country: Czechia
facility: Investigational Site Number : 2030004
city: Hradec Králové
country: Czechia
facility: Investigational Site Number : 2030003
city: Ostrava
country: Czechia
facility: Investigational Site Number : 2030005
city: Pardubice
country: Czechia
facility: Investigational Site Number : 2030002
city: Prague
country: Czechia
facility: Investigational Site Number : 2030001
city: Aarhus
country: Denmark
facility: Investigational Site Number : 2080002
city: Copenhagen
country: Denmark
facility: Investigational Site Number : 2080001
city: Münster
country: Germany
facility: Investigational Site Number : 2760001
city: Budapest
country: Hungary
facility: Investigational Site Number : 3480003
city: Gyor
country: Hungary
facility: Investigational Site Number : 3480004
city: Szeged
country: Hungary
facility: Investigational Site Number : 3480001
city: Haifa
country: Israel
facility: Investigational Site Number : 3760001
city: Amagasaki
country: Japan
facility: Investigational Site Number : 3920007
state: Hyogo
city: Higashimatsuyama
country: Japan
facility: Investigational Site Number : 3920012
state: Saitama
city: Kawagoe
country: Japan
facility: Investigational Site Number : 3920005
state: Saitama
city: Yaizu
country: Japan
facility: Investigational Site Number : 3920014
state: Shizuoka
city: Kodaira
country: Japan
facility: Investigational Site Number : 3920008
state: Tokyo
city: OTA
country: Japan
facility: Investigational Site Number : 3920010
state: Tokyo
city: Saga
country: Japan
facility: Investigational Site Number : 3920009
city: Chihuahua
country: Mexico
facility: Investigational Site Number : 4840002
city: Tlalnepantla de Baz
country: Mexico
facility: Investigational Site Number : 4840001
city: Braga
country: Portugal
facility: Investigational Site Number : 6200003
city: Lisbon
country: Portugal
facility: Investigational Site Number : 6200002
city: Lisbon
country: Portugal
facility: Investigational Site Number : 6200001
city: Oviedo
country: Spain
facility: Investigational Site Number : 7240003
state: Asturias
city: Sabadell
country: Spain
facility: Investigational Site Number : 7240006
state: Castilla Y León
city: Majadahonda
country: Spain
facility: Investigational Site Number : 7240008
state: Madrid
city: Pamplona
country: Spain
facility: Investigational Site Number : 7240002
state: Navarra
city: Málaga
country: Spain
facility: Investigational Site Number : 7240007
city: Valencia
country: Spain
facility: Investigational Site Number : 7240004
city: Stockholm
country: Sweden
facility: Investigational Site Number : 7520001
city: Bern
country: Switzerland
facility: Investigational Site Number : 7560003
city: Kaohsiung City
country: Taiwan
facility: Investigational Site Number : 1580003
city: Taipei City
country: Taiwan
facility: Investigational Site Number : 1580001
city: Bursa
country: Turkey
facility: Investigational Site Number : 7920004
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920001
city: Istanbul
country: Turkey
facility: Investigational Site Number : 7920002
city: Konya
country: Turkey
facility: Investigational Site Number : 7920003
city: Inverness
country: United Kingdom
facility: Investigational Site Number : 8260003
Study officials:
References: