Phase 3 Randomized Double-Blind Trial of Riliprubart Versus Intravenous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy
- Trial ID
- 2023-508338-33-00
- Protocol
- EFC18156
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of riliprubart relative to intravenous immunoglobulin (IVIg) continuation in participants with **Chronic Inflammatory Demyelinating Polyneuropathy** (CIDP), as measured by the INCAT disability scale. This is clinically relevant as it aims to determine whether riliprubart can provide a more effective treatment option for managing disability in CIDP patients compared to the standard IVIg therapy.
Secondary objectives include: - Evaluating the efficacy of riliprubart relative to IVIg continuation as assessed by additional measures of disability and impairment. - Assessing the long-term efficacy of riliprubart through measures of disability and impairment. - Evaluating the efficacy of riliprubart after switching from IVIg continuation. - Assessing the effect of riliprubart relative to IVIg continuation on fatigue, quality of life, and prevention of relapses. - Evaluating the long-term effects of riliprubart on fatigue, quality of life, and prevention of relapses. - Assessing the safety, tolerability, and immunogenicity of riliprubart, including long-term safety and immunogenicity. - Evaluating the delayed efficacy of riliprubart.
Participants
The clinical trial involves a total of **142 participants** diagnosed with **Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific criteria, including a confirmed diagnosis of CIDP or its variants, and a history of treatment with intravenous immunoglobulin (IVIg) within a standard maintenance dosing regimen. The trial does not include a vulnerable population. Participants are required to have a body weight between 35 kg and 154 kg and must have demonstrated a response to IVIg treatment in the past five years. Lifestyle considerations such as diet and physical activity are not specified, but participants must adhere to contraceptive guidelines during and after the study. The trial excludes individuals who are pregnant or breastfeeding, and all participants must have documented vaccinations against encapsulated bacterial pathogens. The selection process ensures that participants have active disease and residual disability as defined by specific clinical scores.
Plans and Procedures
The clinical trial is a **randomized, double-blind, controlled** study designed to evaluate the efficacy and safety of **riliprubart** compared to intravenous immunoglobulin (IVIg) in participants with **Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)**. The trial is structured to include a series of study visits over an estimated duration extending until May 2027, with recruitment anticipated to begin in July 2024. Participants will be involved in the study for a maximum treatment period of 48 weeks, depending on the specific intervention group they are assigned to.
The trial begins with an inclusion (screening) visit, where participants are assessed against the eligibility criteria, which include having a confirmed diagnosis of CIDP and being on a stable IVIg regimen. Following successful screening, participants are randomized to receive either riliprubart or IVIg, with riliprubart administered via **subcutaneous injection** and IVIg via **IV infusion**. The study includes multiple follow-up visits to monitor the participants' response to treatment, assess safety, and collect data on primary and secondary endpoints, such as changes in disability scores and incidence of adverse events.
The end-of-study visit marks the conclusion of the participant's involvement, where final assessments are conducted to evaluate the long-term efficacy and safety of the treatment. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for their safety. The trial aims to provide comprehensive data on the comparative effectiveness of riliprubart and IVIg, contributing valuable insights into the management of CIDP.
Treatment
The clinical trial involves the evaluation of **riliprubart**, an experimental medication, in participants with chronic inflammatory demyelinating polyneuropathy. **Riliprubart** is administered in two pharmaceutical forms: a **solution for injection in a pre-filled pen** and a **solution for injection**. The pre-filled pen form is administered via **subcutaneous injection** with a maximum daily dose of 600 mg and a total dose of 600 mg over a treatment period of 48 weeks. The solution for injection form is administered via **intravenous infusion** with a maximum daily dose of 50 mg/kg and a total dose of 50 mg/kg over a treatment period of 1 week. The active substance, **riliprubart**, is a protein of other origin, and the product is designated as an orphan drug with the designation number EU/3/23/2784.
The comparator treatment in the study is **intravenous immunoglobulin (IVIg)**, classified under the ATC code **J06BA** for normal human immunoglobulins. This treatment is administered as an **intravenous infusion** with a maximum daily dose of 100 mg/kg and a total dose of 1000 mg/kg over a treatment period of 23 weeks. The pharmaceutical form is denoted as **PHF00230MIG**. The specific immunoglobulins, classified under ATC code **J06BB**, are also used in the study with similar dosing and administration parameters.
Additionally, the study includes the use of placebo treatments to ensure the integrity of the double-blind design. The **riliprubart placebo** is available as a solution for injection in both a pre-filled pen and a vial, although specific pharmaceutical forms and routes of administration are not detailed. A **placebo matching IVIg** is also utilized, administered via **intravenous infusion** over a treatment period of 23 weeks. These placebo treatments are essential for maintaining the study's blinding and ensuring unbiased efficacy and safety assessments of the experimental medication.
Efficacy
The efficacy of riliprubart in the treatment of **chronic inflammatory demyelinating polyneuropathy (CIDP)** will be assessed using several primary and secondary endpoints. The primary endpoints include the percentage of participants experiencing a response and the 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 will evaluate changes from baseline in various measures, including the Rasch-built Overall Disability Scale (I-RODS) score, adjusted inflammatory neuropathy cause and treatment (INCAT) disability score, grip strength (kilopascals, dominant hand), Medical Research Council Sum Score (MRC-SS), and the Rasch-built modified fatigue severity scale (RT-FSS). Additionally, the percentage of participants experiencing a relapse, changes in the EuroQol 5 Dimension, 5-Level Health Scale (EQ-5D-5L), and the incidence and titer of anti-drug antibodies (ADA) will be assessed.
Efficacy parameters will be measured and collected at various timepoints throughout the trial, including baseline and subsequent follow-ups. The INCAT disability scale will be used to evaluate the primary objective of the trial, which is to assess the efficacy of riliprubart relative to intravenous immunoglobulin (IVIg) continuation. The trial will also monitor the number of participants with treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs) and adverse events of special interest (AESIs), as well as the number of participants with treatment-emergent ADA in those treated with riliprubart. The trial is designed to provide a comprehensive evaluation of riliprubart's efficacy in managing CIDP, with a focus on both immediate and long-term outcomes.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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 be receiving treatment with IVIg within a standard maintenance dosing regimen, defined as per EAN/PNS 2021 CIDP guidelines.
- 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.
- 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.
- Contraception for sexually active male or female participants; not pregnant or breastfeeding; no sperm donating for male participant.
- Participant must have either typical CIDP, or one of the following 2 CIDP variants: motor 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.
- Participant must be on a stable maintenance dosage of IVIg.
- 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).
Exclusion Criteria
- 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.
- 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.
- 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.
- Recent treatment with plasma exchange.
- Treatment within 3 months prior to dosing with immunosuppressive/ immunomodulator medication, or corticosteroids (with exception of maintenance dose 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.
- Recent use of any specific complement system inhibitor (eg, eculizumab)
- 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.
- Any vaccination received within 28 days prior to dosing (with few exceptions to be confirmed at screening).
- Sensory CIDP, distal CIDP and focal CIDP variants.
- -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 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-HBc Ab] are also positive, indicating natural immunity). -- Anti-hepatitis C virus (anti-HCV) antibodies. Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis RNA test is obtained. --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.
- Any other neurological or systemic disease that can cause symptoms and signs interfering with treatment or outcome assessments.
- Poorly controlled diabetes
- Serious infections requiring hospitalization within 30 days prior to Screening, any active infection requiring antimicrobial 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 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.
- Recent Treatment with efgartigimod.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 22 Jul 2024 | 6 |
 Czechia | Recruiting | 22 Jul 2024 | 16 |
 Denmark | Recruiting | 22 Jul 2024 | 6 |
 France | Recruiting | 22 Jul 2024 | 11 |
 Germany | Recruiting | 22 Jul 2024 | 20 |
 Greece | Not Yet Recruiting | 22 Jul 2024 | 4 |
 Hungary | Recruiting | 22 Jul 2024 | 9 |
 Italy | Not Yet Recruiting | 22 Jul 2024 | 10 |
 Norway | Not Yet Recruiting | 22 Jul 2024 | 6 |
 Poland | Not Yet Recruiting | 22 Jul 2024 | 6 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
- | Comparator | PHF00230MIG | IV INFUSION | 100 | 23 | J06BA |
placebo matching IVIg | Placebo | N/A | IV INFUSION | — | 23 | N/A |
riliprubart placebo solution for injection in vial | Placebo | N/A | — | — | — | N/A |
riliprubart | Test | SOLUTION FOR INJECTION | IV INFUSION | 50 | 1 | PRD10878079 |
riliprubart | Test | SOLUTION FOR INJECTION IN PRE-FILLED PEN | SUBCUTANEOUS INJECTION | 600 | 48 | PRD10875707 |
riliprubart placebo solution for injection in prefilled pen | Placebo | N/A | — | — | — | N/A |
- | Comparator | PHF00230MIG | IV INFUSION | 100 | 23 | J06BB |