E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired paralytic illness affecting peripheral nerves and caused by a demyelinating process. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057645 |
E.1.2 | Term | Chronic inflammatory demyelinating polyradiculoneuropathy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to assess the efficacy of I10E in improving the disability of patients with CIDP.
|
|
E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess the safety of I10E in patients with CIDP.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 :
a)has never been previously treated with Ig (Ig-naïve patient)
OR
b) 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.
5. Covered by national healthcare insurance system as required by
local regulations.
6. Written informed consent obtained prior to any study-related
procedures. |
|
E.4 | Principal exclusion criteria |
1. History of severe allergic reaction or serious adverse reaction
to any immunoglobulin (Ig).
2. Clinically documented lack of response to previous Ig
treatment.
3. History of IgA deficiency (IgA ≤ 70 mg/L), unless the absence of anti-IgA antibodies has been documented.
4. Known hypersensitivity to human Ig or to any of the
excipients of I10E (glycine and polysorbate 80).
5. History of cardiac insufficiency (New York Heart
Association [NYHA] III/IV), uncontrolled cardiac
arrhythmia, unstable ischemic heart disease, or uncontrolled
hypertension.
6. History of venous thrombo-embolic disease, myocardial
infarction or, cerebrovascular accident.
7. Risk factor for blood hyperviscosity such as
cryoglobulinemia or haematologic malignancy with
monoclonal gammopathy.
8. History of personal or familial congenital thrombophilia or
acquired thrombophilia.
9. Factors contributing to venous stasis such as long-term bed
confinement.
10. Body Mass Index (BMI) ≥ 40 kg/m².
11. Protein-losing enteropathy characterised by serum protein levels < 60 g/L and serum albumin levels < 30 g/L.
12. History of kidney transplantation, nephrotic syndrome (defined as proteinuria > 3.5 g per 24 hours accompanied by hypoalbuminemia and edema), or any acute or chronic kidney disease that in the opinion of the investigator and/or nephrologist would preclude the use of I10E and/or interfere with the assessment of the safety and efficacy of I10E.
AND/OR
*Chronic kidney disease (CKD) for more than 3 months as documented by at least one of the following:
*glomerular filtration rate (GFR) < 60 mL/min/1.73m2 measured according to the Modified Diet in Renal Disease (MDRD) formula
AND/OR
*urine protein reagent strip: ≥ 2 crosses
AND/OR
*urine protein reagent strip: one cross with one of the following:
*albumin excretion rate (AER) > 300 mg/24 hours or protein excretion rate (PER) > 500 mg/24 hours (24h-urine collection)
OR
*albumin to creatinine ratio (ACR) >30 mg/mmol or protein to creatinine ratio (PCR) > 50 mg/mmol (spot urine sample).
13. Serum levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times upper limit of normal (ULN) range.
14.Any other ongoing disesase that may cause chronic peripheral neuropathy, such as toxin exposure, dietary deficienct, 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, Waldenstrom's macroglobulinaemia, amyloidosis, and hereditary neuropathy.
15.Woman with positive results on a urine pregnancy test or breastfeeding women or women of childbearing potential without an effective contraception.
Effective contraceptives are injectable, patch or oral combined oestron progestative or progestative contraceptives, Cooper T or levonorgest releasing intra-uterine devices, depot intramuscular medroxyprogesterone, subcutaneous progestative contraceptive implants, condoms or occlusive caps (diaphragm or cervical/vault caps) with spermicide, true abstinence (when this is in line with the preferred and usual lifestyle of the patient).
16.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.
17.Increasing dosage or introduction of a systemic corticoids therapy , or corticosteroids therapy at a dose higher than 10 mg prednisolone per day or equivalent within the last 3 months prior screening. Topical corticosteroids are permitted.
18.Treatment within 12 months prior to screening with immunomodulatory or immunosupressant agents (including but not limited to cyclophosphamide, cyclosporine, interferon-a, interferon-B1a, anti-CD20, alemtuzumab, aziathioprine, etanercept, mycophenolate mofetil, methotrexate or haemopoetic stem cell transplantation.
19. Plasma exchange, blood products or derivatives administered within the last 3 months prior to screenin.
20. Administration of another investigational product within the last month prior to screening.
21. Drug or alcool abuse.
22. Anticipated poor compliance of patient with study procedures. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Responder rate at EOS visit.
Responders are defined as patients with a decrease ≥1 point in the
adjusted INCAT score between baseline and the EOS visit. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
at baseline and the End Of Study visit. |
|
E.5.2 | Secondary end point(s) |
- Responder rate at 12 weeks.
- Time to response.
- Percentage of patients at 12 weeks and EOS visit with no change in
CIDP treatment.
- Changes from baseline to 12 weeks and EOS visit in the following
scores:
• Adjusted INCAT disability score;
• Grip strength with the Martin vigorimeter in both hands;
• Rasch-built Overall Disability Scale (R-ODS);
• Patient and Investigator Clinical Global Impression (CGI);
• Medical Research Council (MRC) 12 muscles sum score (0 to 5) and Rasch-modified MRC (0 to 3). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, at 12 weeks and End of study visit |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Other exploratory objectives are to assess:
- To assess a potential relationship between total serum IgG trough levels, biomarkers levels and clinical changes – as assessed by neurological scales – in patients with CIDP.
- To assess a potential relationship between ultrasonography (USG) coupled to neurophysiology analysis of nerves and clinical responses– as assessed by neurological scales – in patients with CIDP (ancillary study in Italy). |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 33 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Germany |
Italy |
Poland |
Spain |
Tunisia |
Turkey |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |