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)

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

1 Oct 2024 → ongoing

Decision date (initial)

2024-07-22

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2023-508338-33-00

WHO UTN

U1111-1295-3363

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

- To evaluate the efficacy of riliprubart relative to IVIg continuation as measured by the INCAT disability scale
- To evaluate long-term efficacy of riliprubart as measured by the INCAT disability scale

Secondary objectives 17

1. To evaluate the efficacy of riliprubart relative to IVIg continuation as assessed by additional measures of disability
2. To evaluate long-term efficacy of riliprubart as assessed by additional measures of disability
3. To evaluate the efficacy of riliprubart after switching from IVIg continuation
4. To evaluate the efficacy of riliprubart relative to IVIg continuation as assessed by measures of impairment
5. To evaluate long-term effect of riliprubart as assessed by measures of impairment
6. To evaluate the effect of riliprubart relative to IVIg continuation on fatigue
7. To evaluate long-term effect of riliprubart on fatigue
8. To evaluate the effect of riliprubart relative to IVIg continuation on prevention of relapses
9. To evaluate long-term effect of riliprubart on prevention of relapses
10. To evaluate effect of riliprubart on prevention of relapses after switching from IVIg continuation
11. To evaluate the effect of riliprubart relative to IVIg continuation on quality of life
12. To evaluate long-term effect of riliprubart on quality of life
13. To evaluate the safety and tolerability of riliprubart
14. To evaluate the long-term safety and tolerability of riliprubart
15. To evaluate the immunogenicity of riliprubart
16. To evaluate long-term immunogenicity of riliprubart
17. To evaluate delayed efficacy of riliprubart

Conditions and MedDRA coding

Chronic Inflammatory Demyelinating Polyneuropathy

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 15

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. All participants must agree to use contraception methods during and after the study as required.
3. 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.
4. -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.
5. -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.
6. 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.
7. 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.
8. 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.
9. 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).
10. 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).
11. 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.
12. Participant must have active disease, defined by a CIDP disease activity score (CDAS) of ≥2 points at Screening.
13. 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.
14. Participant must have a body weight at Screening of 35 kg to 154 kg (77 to 340 lbs) inclusive.
15. 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 28

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. 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.
3. Evidence of CIDP worsening within the 6 weeks following a prior vaccination that, in the opinion of the Investigator, constituted a relapse.
4. Recent or planned major surgery that could confound the results of the trial or put the participant at undue risk.
5. Treatment with plasma exchange within 8 weeks prior to Screening.
6. 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).
7. Prior treatment with riliprubart.
8. 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.
9. Prior treatment (any time) with total lymphoid irradiation or bone marrow transplantation.
10. 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.
11. Any vaccination received within 28 days prior to dosing (with few exceptions to be confirmed at screening).
12. Sensory CIDP, distal CIDP and focal CIDP variants.
13. -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.
14. 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.
15. Positive result of any of the following tests: --HBsAg. --Anti-HBc Ab; unless anti-HBs Ab are also positive, indicating natural immunity. --Anti-HCV antibodies. --Anti-HIV1 and anti-HIV2 antibodies.
16. Pregnancy, defined as a positive result of a highly sensitive urine or serum pregnancy test, or lactation.
17. Accommodation in an institution because of regulatory or legal order; imprisoned or legally institutionalized.
18. 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.
19. 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.
20. Any country-related specific regulation that would prevent the participant from entering the study as defined by the protocol.
21. Any other neurological or systemic disease that can cause symptoms and signs interfering with treatment or outcome assessments.
22. Poorly controlled diabetes (HbA1c >7% at the Screening visit)
23. 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).
24. 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.
25. 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.
26. 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).
27. 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.
28. Treatment with efgartigimod within 8 weeks prior to screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Percentage of participants experiencing a response
2. Percentage of participants randomized to riliprubart who responded during part A and had a lasting response during the open-label treatment extension period.

Secondary endpoints 21

1. Change from baseline in 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. Change from baseline in the Rasch-built modified fatigue severity scale (RT-FSS)
6. Percentage of participants experiencing a relapse
7. Change from baseline in the EuroQol 5 Dimension, 5-Level Health Scale (EQ-5D-5L)
8. Number of participants with TEAEs, including SAEs and AESIs for Part A.
9. Number of participants with treatment-emergent ADA in participants treated with riliprubart
10. Number of participants with TEAEs, including SAEs and AESIs
11. Percentage of participants randomized to riliprubart experiencing a relapse
12. Percentage of participants randomized to IVIg continuation experiencing a relapse
13. Incidence and titer of anti-drug antibodies (ADA) during open-label treatment and follow-up.
14. Change from baseline in I-RODS
15. Change from baseline in adjusted INCAT score
16. Change from baseline in grip strength (kilopascals; dominant hand)
17. Change from baseline in MRC-SS
18. Change from baseline in RT-FSS
19. Change from baseline in EQ-5D-5L score
20. Percentage of participants randomized to riliprubart who experienced a response at Week 48 without prior response in Part A (delayed response)
21. Percentage of participants randomized to IVIg continuation who experience a response

Investigational products

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

Test 2

Comparator 2

Placebo 3

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 Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 8

Locations

13 EU/EEA countries · 53 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 260 files

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

Application history

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