A study to test the effects and safety of riliprubart in people with chronic inflammatory demyelinating polyneuropathy (CIDP) for which the usual treatments do not work

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

31 Jul 2024 → ongoing

Decision date (initial)

2024-06-18

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-506503-26-00

WHO UTN

U1111-1295-5755

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

• To evaluate the efficacy of riliprubart relative to placebo as measured by the Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale
• To evaluate long-term efficacy of riliprubart as measured by the INCAT disability scale

Secondary objectives 14

1. To evaluate the efficacy of riliprubart relative to placebo as assessed by additional measures of disability
2. To evaluate long-term efficacy of riliprubart with additional measures of disability
3. To evaluate the efficacy of riliprubart relative to placebo as assessed by measures of impairment
4. To evaluate long-term efficacy of riliprubart with additional measures of impairment
5. To evaluate the efficacy of riliprubart relative to placebo in immunoglobulin-refractory participants as measured by the INCAT disability scale
6. To evaluate the effect of riliprubart relative to placebo on quality of life
7. To evaluate long-term effect of riliprubart on quality of life
8. To evaluate the effect of riliprubart relative to placebo on fatigue
9. To evaluate long-term effect of riliprubart on fatigue
10. To evaluate the safety and tolerability of riliprubart
11. To evaluate long-term safety and tolerability of riliprubart
12. To evaluate the immunogenicity of riliprubart
13. To evaluate long-term immunogenicity of riliprubart
14. To evaluate delayed efficacy of riliprubart

Conditions and MedDRA coding

Polyneuropathy, Inflammatory Demyelinating, Chronic

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

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 analysys 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 can be found at: https://vivli.org

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 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).
2. 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. -- Male participants are 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 --- 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 as described in the protocol. -- 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 woman of childbearing potential (WOCBP) and agrees to use a contraceptive method that is highly effective (with a failure rate of <1% per year), as described in Appendix 10.4 Contraception and barrier guidance 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.
3. Participant must have either typical CIDP, or one of the following two CIDP variants: motor CIDP (including motor predominant), multifocal CIDP (also known as Lewis Sumner Syndrome). Diagnosis must be confirmed by the adjudication committee.
4. Participant must be refractory to either immunoglobulin therapy or corticosteroid therapy, as defined below.--Immunoglobulin-refractory subgroup: Historic evidence of failure or inadequate response to immunoglobulin therapy prior to screening, defined as no clinically meaningful improvement or persistent INCAT score ≥2 after a minimum of: ---One dose of IVIg of 2 g/kg, followed by either a second dose of 2 g/kg, or at least 2 doses of 1 g/kg, with a separation of approximately 3 weeks between doses (each dose can be divided over 2 to 5 days), as indicated in the EAN/PNS 2021 guidelines OR ---SCIg maintenance therapy with at least 0.2 g/kg weekly for 5 weeks --Corticosteroid-refractory subgroup: Historic evidence of failure or inadequate response to corticosteroid therapy prior to screening, defined as no clinically meaningful improvement or persistent INCAT score ≥2 after a minimum of 12 weeks of corticosteroid therapy. Corticosteroid regimen can be daily oral prednisone/prednisolone, at least 60 mg, equivalent to methylprednisolone 48 mg, tapered over 6 to 8 months, or alternative regimens, e.g. pulsed high-dose corticosteroid treatment (40 mg/day oral dexamethasone or 500 mg/day IV methylprednisolone, each daily for 4 days per month for 6 months), as indicated in the EAN/PNS 2021 guidelines A clinically meaningful improvement is defined as one or more of the following: ---A ≥1 point decrease in adjusted INCAT disability score ---An increase in I-RODS centile score ≥4 points ---An increase in MRC Sum score ≥3 points ---An improvement in hand grip strength of ≥8 kilopascals or ---Equivalent improvement based on information from medical records and per the Investigator’s judgment
5. Participant has an INCAT score of 2 to 9 (a score of 2 should be exclusively from the leg disability component of INCAT).
6. Any allowed immunosuppressant drugs (azathioprine, cyclosporine, or mycophenolate mofetil) have been taken for ≥6 months at a stable dose for ≥3 months prior to Screening
7. Participant may be receiving low-dose oral corticosteroids (≤20 mg/day of prednisone [or equivalent dose for other oral corticosteroids]), but only if taken at a stable dose for ≥3 months prior to Screening
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. A body weight at Screening of 35 kg to 154 kg (77 to 340 lbs), inclusive

Exclusion criteria 29

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 Immunoglobulin M (IgM) monoclonal gammopathy, POEMS syndrome, and lumbosacral radiculoplexus neuropathy.
2. Evidence of CIDP worsening within the 6 weeks following a prior vaccination that, in the opinion of the Investigator, constituted a relapse
3. Recent or planned major surgery that could confound the results of the trial or put the participant at undue risk
4. Participant has received immunoglobulins (IVIg or SCIg) within 12 weeks prior to Screening
5. Treatment with plasma exchange within the 8 weeks prior to Screening
6. Prior treatment with riliprubart
7. Prior treatment with (any time) with highly immunosuppressive/chemotherapeutic medications with sustained effects, eg, mitoxantrone, alemtuzumab, cladribine
8. Prior treatment (any time) with total lymphoid irradiation or bone marrow transplantation
9. 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
10. 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
11. Treatment within 6 months prior to dosing with immunosuppressive/ chemotherapeutic medications, such as cyclophosphamide, methotrexate, tacrolimus, interferon, or tumor necrosis factor (TNF)-α inhibitors. Certain immunosuppressants commonly used in CIDP (azathioprine, cyclosporine, or mycophenolate mofetil) are allowed, as indicated under inclusion criterion.
12. Sensory CIDP, Distal CIDP and focal CIDP variants.
13. Any vaccination received within 28 days prior to dosing (with few exceptions to be confirmed at screening)
14. 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
15. 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.
16. 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
17. Pregnancy, defined as a positive result of a highly sensitive urine or serum pregnancy test, or lactation
18. Accommodation in an institution because of regulatory or legal order; eg, imprisoned or legally institutionalized
19. Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or potential risk for noncompliance to study procedures
20. Participants are employees at the clinical study site or other individuals directly involved in the conduct of the study, or immediate family member of such individuals
21. Any country related specific regulation that would prevent the participant from entering the study
22. Any other neurological or systemic disease that can cause symptoms and signs interfering with treatment or outcome assessments
23. Poorly controlled diabetes (HbA1c >7% at the Screening visit)
24. Serious infections requiring hospitalization within 30 days prior to Screening and 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)
25. 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.
26. 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.
27. Any other clinically meaningful medical history or ongoing medical condition (as determined by the Investigator at Screening) that might impact 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 Investigator’s judgment.
28. Documented history of attempted suicide over the 6 months prior to the Screening visit, presence of suicidal ideation of category 4 or 5 on C-SSRS during screening, OR if in the Investigator’s judgment, the participant is at risk for a suicide attempt.
29. Treatment with efgartigimod within 8 weeks prior to screening

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Percentage of participants experiencing a response
2. Percentage of participants randomized to riliprubart with lasting response
3. Percentage of participants randomized to placebo who experience a response

Secondary endpoints 18

1. Change from baseline in Inflammatory Rasch-built Overall Disability Scale (I-RODS) score
2. Change from baseline in adjusted inflammatory neuropathy cause and treatment (INCAT) disability score
3. Change from baseline in grip strength (kilopascals; dominant hand)
4. Change from baseline in Medical Research Council Sum Score (MRC-SS)
5. Percentage of participants refractory to immunoglobulins experiencing a response
6. Change from baseline in the EuroQol 5 Dimension, 5-Level Health Scale (EQ-5D-5L)
7. Change from baseline in the Rasch-built modified fatigue severity scale (RT-FSS)
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
9. Incidence and titer of anti-riliprubart antibodies (ADA)
10. Number of participants with TEAEs, including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) for Part B
11. Incidence and titer of anti-riliprubart antibodies
12. Change from baseline in I-RODS score
13. Change from baseline in adjusted INCAT score
14. Change from baseline in grip strength (kilopascals; dominant hand)
15. Change from baseline in MRC-SS
16. Change from baseline in EQ-5D-5L score
17. Change from baseline in RT-FSS
18. Percentage of participants randomized to riliprubart who experience a response at Week 48 without prior response in Part A (delayed response)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Research & Development

Contact name

Clinical Sciences and Operations

Third parties 7

Locations

13 EU/EEA countries · 54 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 286 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

28 submissions — initial application plus substantial / non-substantial modifications