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. |
|
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 | 20.0 |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The study is descriptive. The primary objective is to assess the efficacy of I10E administered at a reduced maintenance dose in sustaining CIDP response after an initial 6-month treatment in PRISM study. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective is to assess the safety of I10E in this patient population. |
|
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. Responder patient who have completed the last visit of PRISM I10E-1302 study defined as a patient with a decrease ≥1 point in the adjusted INCAT disability score between baseline and the end-of-study (EOS) visit of PRISM I10E-1302 study.
3. Covered by national healthcare insurance system as required
by local regulations.
4. Written informed consent obtained prior to any study-related
procedures. |
|
E.4 | Principal exclusion criteria |
Based on follow-up and results of analyses performed in PRISM
I10E-1302 study, a patient may be eligible in PRISM 2 I10E-1306
study if none of the following criteria is met:
1. History of severe allergic reaction or serious adverse reaction to
any Ig.
2. Known hypersensitivity to human Ig or to any of the excipients of I10E (glycine and polysorbate 80).
3. History of cardiac insufficiency (New York Heart Association (NYHA) III/IV), uncontrolled cardiac arrhythmia, unstable ischemic heart disease, or uncontrolled hypertension.
4. History of venous thromboembolic disease, myocardial infarction or cerebrovascular accident.
5. Risk factor for blood hyperviscosity such as cryoglobulinemia or haematological malignancy with monoclonal gammopathy.
6. History of personal or familial congenital thrombophilia or acquired thrombophilia.
7. Factors contributing to venous stasis such as long-term bed confinement.
8. Body mass index (BMI) ≥40 kg/m².
9. Protein-losing enteropathy characterised by total serum protein levels <60
g/L and serum albumin levels <30 g/L
10. 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:
or albumin excretion rate (AER) >300 mg/24 hours
or protein excretion rate (PER) >500 mg/24 hours (24h-urine collection)
OR
or albumin to creatinine ratio (ACR) >30 mg/mmol
or protein to creatinine ratio (PCR) >50 mg/mmol (spot urine sample).
11. Serum levels of Alanine aminotransferase (ALT) or Aspartate
aminotransferase (AST) >2 times upper limit of normal range (ULN).
12. 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, amyloidosis, and hereditary neuropathy.
13. Woman with positive results on a urine pregnancy test or breastfeeding woman or woman of childbearing potential without an effective contraception. Effective contraceptives are injectable, patch or combined oestro-progestative or progestative contraceptives, Copper 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).
14. 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.
15. Increasing dosage or introduction of a systemic corticosteroids
therapy, or corticosteroids therapy at a dose higher than 10 mg per day prednisolone, or equivalent within the last 3 monthsprior to screening (in I10E-1302 Clinical Study). Topical corticosteroids are permitted.
16. Treatment within 12 months prior to screening with
immunomodulatory or immunosuppressant agents (including but not
limited to cyclophosphamide, cyclosporine, interferon-α, interferon-β1a, anti-CD20, alemtuzumab, aziathioprine, etanercept, mycophenolate mofetil and methotrexate) or haemopoetic stem cell transplantation.
17. Plasma exchange, blood products or derivatives administered within
the last 3 months prior to screening.
18. Drug or alcohol abuse.
19. Anticipated poor compliance of patient with study procedures.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the responder rate at EOS
visit.
Responders are defined as patients with either:
- No change or decrease in the adjusted INCAT disability score and without any change in CIDP treatment between baseline and EOS visit.
or
- An increase by 1 point in the adjusted INCAT disability score without requirement of any change in CIDP treatment between baseline and EOS visit. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the inclusion (baseline), end of study visit |
|
E.5.2 | Secondary end point(s) |
Main secondary efficacy endpoints:
− Change from baseline to 24 weeks (Visit V9) and EOS visit in the adjusted INCAT disability score.
− Responder rate at 24 weeks (visit V9).
− Time to relapse.
− Change from baseline to 24 weeks (Visit V9) and EOS visit in the following scores:
▪ Grip strength with the Martin Vigorimeter in both hands;
▪ Rasch-built Overall Disability Scale (R-ODS);
▪ Medical Research Council (MRC) 12 muscles sum score
(0 to 5) and Rasch-modified MRC (0 to 3).
Other secondary endpoints:
- Percentage of patients at 24 weeks (Visit V9) and EOS visit with no requirement of change in CIDP treatment from baseline.
- Change from baseline to 24 weeks (Visit V9) and EOS visit in Patient and Investigator Clinical Global Impression (CGI). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At the inclusion, at week 24 and at the 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 |
Exploratory objectives:
• To assess a potential relationship between serum total IgG trough
levels, biomarkers levels and clinical response, as assessed by
neurological scales, in patients with CIDP.
• To assess a potential relationship between ultrasonography (US)
coupled to neurophysiology analysis of nerves and clinical response, as
assessed by neurological scales, in patients with CIDP (ancillary study in Italy only). |
|
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 16 |
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 |
Italy |
Spain |
Tunisia |
Turkey |
United Kingdom |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
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 | 3 |