A study to investigate the efficacy and safety of Riliprubart compared to standard treatment with intravenous immunoglobulin in people with chronic inflammatory demyelinating polyneuropathy.

Argentina, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Mexico, Norway, Portugal, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey (T�rkiye), United Kingdom, United States (ICTRP)

Identifiant de l'essai ICTRP
NCT06290141 (ICTRP)

Titre officiel (approuvé par le comité d'éthique)
A Phase 3, randomized, double-blind, study evaluating efficacy and safety of Riliprubart versus intravenous immunoglobulin (IVIg) in participants with chronic inflammatory demyelinating polyneuropathy (BASEC)

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

Titre public
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) (ICTRP)

Maladie en cours d'investigation
Chronic Inflammatory Demyelinating Polyneuropathy (ICTRP)

Intervention étudiée
Drug: riliprubartDrug: PlaceboDrug: riliprubartDrug: PlaceboDrug: IVIgDrug: Placebo (ICTRP)

Type d'essai
Interventional (ICTRP)

Plan de l'étude
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)

Critères d'inclusion/exclusion
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-Barr 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 (ICTRP)

non disponible

Critères d'évaluation principaux et secondaires
Percentage of participants experiencing a response;Percentage of participants randomized to riliprubart who responded during part A and had a lasting response during the open-label treatment extension period (ICTRP)

Change from baseline in Rasch-built Overall Disability Scale (I-RODS) score;Change from baseline in adjusted inflammatory neuropathy cause and treatment (INCAT) disability score;Change from baseline in grip strength (kilopascals, dominant hand);Change from baseline in Medical Research Council Sum Score (MRC-SS);Change from baseline in the Rasch-built modified fatigue severity scale (RT-FSS);Percentage of participants experiencing a relapse;Change from baseline in the EuroQol 5 Dimension, 5-Level Health Scale (EQ-5D-5L);Number of participants with TEAEs, including SAEs and AESIs for Part A;Number of participants with treatment-emergent ADA in participants treated with riliprubart;Number of participants with TEAEs, including SAEs and AESIs;Incidence and titer of anti-drug antibodies (ADA) during open-label treatment and follow-up;Change from baseline in I-RODS;Change from baseline in adjusted INCAT score;Change from baseline in grip strength (kilopascals; dominant hand);Change from baseline in MRC-SS;Change from baseline in EQ-5D-5L score;Percentage of participants randomized to IVIg continuation who experienced a response;Percentage of participants randomized to riliprubart who experienced a response at Week 48 without prior response in Part A (delayed response);Percentage of participants randomized to riliprubart experiencing a relapse;Change from baseline in RT-FSS;Percentage of participants randomized to riliprubart experiencing a relapse (ICTRP)

Date d'enregistrement
non disponible

Inclusion du premier participant
non disponible

Sponsors secondaires
non disponible

Contacts supplémentaires
Trial Transparency email recommended (Toll free for US & Canada), contact-us@sanofi.com, 800-633-1610 (ICTRP)

ID secondaires
U1111-1295-3363, 2023-508338-33, EFC18156 (ICTRP)

Résultats-Données individuelles des participants
non disponible

Informations complémentaires sur l'essai
https://clinicaltrials.gov/study/NCT06290141 (ICTRP)