Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Conditions
Keywords
Peripheral neuropathy, Disimmune disease, Neurology Chronic disease, Rare disease
Brief summary
Primary objective: To assess the efficacy of I10E in improving the disability of patients with CIDP. Secondary objective: To assess the safety of I10E in patients with CIDP.
Interventions
DRUGI10E
Patients who meet all eligibility criteria will receive one dose of IMP at 2g/kg over 2-5 days followed by 7 doses of IMP at 1g/kg over 1-2 day(s), every 3 weeks. Duration of treatment period: 21 weeks +/- 7 days.
Sponsors
Laboratoire français de Fractionnement et de Biotechnologies
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patient aged 18 years or more 2. Definite or probable CIDP according to the European Federation of Neurological Societies (EFNS)/Peripheral Nerve Society (PNS) guidelines 2010 clinical and neurophysiological criteria Pure motor CIDP, provided that a diagnosis of multifocal motor neuropathy has been ruled out CIDP associated with monoclonal gammopathy of undetermined significance (MGUS), provided that anti-MAG antibodies titer is lower than the used technique's negativity threshold (1000 BTU for Bühlmann ELISA technique) Lewis-Sumner syndrome 3. Score of at least 2 on the adjusted INCAT disability scale 4. Patient who either : 1. has never been previously treated with Ig (Ig-naive patient) Or 2. was previously treated with Ig but is in clinical relapse following treatment withdrawal. In the latter case, the last Ig course shall have been administered no less than 3 months prior to screening
Exclusion criteria
1. History of IgA deficiency, unless the absence of anti-IgA antibodies has been documented 2. History of cardiac insufficiency (New York Heart Association \[NYHA\] III/IV), uncontrolled cardiac arrhythmia, unstable ischemic heart disease, or uncontrolled hypertension 3. History of venous thrombo-embolic disease, myocardial infarction or, cerebrovascular accident 4. Risk factor for blood hyperviscosity such as cryoglobulinemia or haematologic malignancy with monoclonal gammopathy 5. Body mass Index (BMI) ≥40 kg/m² 6. Glomerular filtration rate \<80 mL/min/1.73m² measured according to the Modified Diet in Renal Disease (MDRD) calculation 7. Any other ongoing disease that may cause chronic peripheral neuropathy, such as toxin exposure, dietary deficiency, uncontrolled diabetes, hyperthyroidism, cancer, systemic lupus erythematosus or other connective tissue diseases, infection with HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV), Lyme disease, multiple myeloma, Waldenström's macroglobulinaemia, amyloid, and hereditary neuropathy 8. Woman with positive results on a urine pregnancy test or breastfeeding woman or woman of childbearing potential without an effective contraception. 9. Any other serious medical condition that would interfere with the clinical assessment of CIDP or use of I10E or prevent the patient from complying with the protocol requirements 10. Increasing dosage or introduction of a corticotherapy within the last 3 months prior to screening, with oral or systemic corticosteroids at a dose higher than 10 mg daily prednisolone or equivalent. Topical corticosteroids are permitted 11. Treatment within 12 months prior to screening with immunomodulatory or immunosuppressant agents (including but not limited to cyclophosphamide, cyclosporine, interferon-alfa, interferon-beta1a, anti-CD20, alemtuzumab, aziathioprine, etanercept, mycophenolate mofetil, methotrexate and haemopoetic stem cell transplantation) 12. Plasma exchange, blood products or derivatives administered within the last 3 months prior to screening 13. Administration of another investigational product within the last month prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Endpoint: Responder Rate at End of Study | 24 weeks after first treament injection | Responders were defined as patients with a decrease ≥1 point in the adjusted INCAT disability score compared to baseline. Adjusted INCAT disability score can vary from 0 (normal) to 9 (maximal disability). If a patient was treated with a not-allowed treatment during the study period, then all adjusted INCAT disability score measured after the intake of these not-allowed treatments were censored. If the score at EoS visit was missing, then the Last Observation Carried Forward (LOCF) approach was applied to replace this missing value. |
Countries
France, Italy, Spain, Tunisia, Turkey (Türkiye), United Kingdom
Participant flow
Recruitment details
Between 24 February 2015 and 22 March 2017, 59 subjects from 23 sites signed an informed consent.
Pre-assignment details
59 subjects signed an informed consent in the pre-assigment period. Among them, 18 subjects were considered as a screening failure including 3 subjects re-screened and finally enrolled. Of 44 enrolled subjects, on subject was discontinued (consent withdrawn by subject) from the study before the first administration of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Total Treated Set All subjects who received at least one infusion of I10E | 43 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Total Treated Set |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants |
| Age, Continuous | 50.0 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 19 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Region of Enrollment France | 2 participants |
| Region of Enrollment Italy | 16 participants |
| Region of Enrollment Poland | 8 participants |
| Region of Enrollment Spain | 6 participants |
| Region of Enrollment Tunisia | 8 participants |
| Region of Enrollment Turkey | 2 participants |
| Region of Enrollment United Kingdom | 1 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 43 |
| other Total, other adverse events | 39 / 43 |
| serious Total, serious adverse events | 7 / 43 |
Outcome results
Primary
Efficacy Endpoint: Responder Rate at End of Study
Responders were defined as patients with a decrease ≥1 point in the adjusted INCAT disability score compared to baseline. Adjusted INCAT disability score can vary from 0 (normal) to 9 (maximal disability). If a patient was treated with a not-allowed treatment during the study period, then all adjusted INCAT disability score measured after the intake of these not-allowed treatments were censored. If the score at EoS visit was missing, then the Last Observation Carried Forward (LOCF) approach was applied to replace this missing value.
Time frame: 24 weeks after first treament injection
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Full Analysis Set | Efficacy Endpoint: Responder Rate at End of Study | 32 Participants |
Comparison: For this single-arm study, the response rate was tested against the historical response rate of 33.3% with a 1-sided Clopper-Pearson exact test at the nominal level of significance of 2.5% on the Full Analysis Set. The null and alternative hypotheses were as follows:~H0: pI10E \<= 33.3% H1: pI10E \> 33.3%p-value: <0.000195% CI: [60.5, 87.9]exact binomial Clopper-Pearson