An international study on efficacy and safety of I10E in CIDP patients

• Register: EUCTR
• Last refreshed on: 30 April 2019
• Main ID: EUCTR2013-005557-73-GB
• Date of registration: 15/08/2014
• Prospective Registration: Yes
• Primary sponsor: LFB BIOTECHNOLOGIES
• Public title: An international study on efficacy and safety of I10E in CIDP patients
• Scientific title: An international, multicentre, efficacy and safety study of I10E in initial and maintenance treatment of patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy - PRISM
• Date of first enrolment: 21/10/2014
• Target sample size: 42
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-005557-73
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Single arm; If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Italy, Spain, Tunisia, Turkey, United Kingdom

Contacts

• Name: Clinical trial information desk
• Affiliation: LFB BIOTECHNOLOGIES

• Name: Clinical trial information desk
• Affiliation: LFB BIOTECHNOLOGIES

Key inclusion & exclusion criteria

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-naive 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 38
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

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 total serum protein levels <60 g/L and serum albumin levels <30 g/L or nephrotic syndrome characterised by proteinuria =3.5 g/24hours, 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 that 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 <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 ration (ACR) >30mg/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 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, HBV or HCV, Lyme disease, multiple myeloma, Waldenström's macroglobulinaemia, amyloid, and hereditary
neuropathy.
15. Woman with positive results on a urine pregnancy test or breastfeeding woman or woman of childbearing potential without an effective contraception.
Effective contraceptive are injectables, patch or oral combinded o eston progestative or progestative contraceptives, Cooper T or levonorgest releasing intra-uterine devices, depot intramuscular medroxyprogest

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)
MedDRA version: 20.0 Level: PT Classification code 10057645 Term: Chronic inflammatory demyelinating polyradiculoneuropathy System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: IQYMUNE
Product Name: human normal immunoglobulin for intravenous administration
Product Code: I10E
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: HUMAN NORMAL IMMUNOGLOBULIN (IV)
Current Sponsor code: I10E
Other descriptive name: HUMAN NORMAL IMMUNOGLOBULIN (IV)
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Secondary Objective: The secondary objective is to assess the safety of I10E in patients with CIDP.

Main Objective: The primary objective of this study is to assess the efficacy of I10E in improving the disability of patients with CIDP.

Primary end point(s): Responder rate at EOS visit.
Responders are defined as patients with a decrease =1 point in the adjusted INCAT disability score between baseline and the EOS visit.

Timepoint(s) of evaluation of this end point: at baseline and the End Of Study visit.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline, at 12 weeks and End of study visit

Safety endpoints will be assessed from first IMP administration through EOS visit, as well as by assessment of clinically significant changes from baseline in vital signs and laboratory tests.

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).

Safety Endpoints:
Safety will be evaluated by the assessement of AEs and TAAEs – including SAEs – from first IMP administration through EOS visit, as well as by assessment of clinically significant changes from baseline in vital signs and laboratory tests.

Secondary ID(s)

I10E-1302

Source(s) of Monetary Support

LFB BIOTECHNOLOGIES

Ethics review

Status: Approved
Approval date:
Contact: