A multinational study with I10E (Human Immunoglobulin) to demonstrate the efficacy and the safety of the product in patients suffering from deficiency in their immune system

• Conditions: a primary immunodeficiency as defined by the ESID and validated by a reference centre :• X-linked agammaglobulinemia (XLA)• Common variable immunodeficiency (CVID); MedDRA version: 16.1Level: LLTClassification code 10010112Term: Common variable immunodeficiencySystem Organ Class: 100000004870; MedDRA version: 16.1Level: HLTClassification code 10036700Term: Primary immunodeficiency syndromesSystem Organ Class: 100000004870; MedDRA version: 16.1Level: LLTClassification code 10001471Term: AgammaglobulinemiaSystem Organ Class: 100000004870; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2010-023483-41-Outside-EU/EEA
• Lead Sponsor: FB BIOTECHNOLOGIES

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-04-11
• Last Update Posted: 14 April 2014

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Both genders
2. Age between 2 to 65 year old
3. Has an humoral primary immunodeficiency as defined by the ESIDs1
and validated by the reference centers :
· X-linked agammaglobulinemia (XLA)
· Common variable immunodeficiency (CVID)
4. The requirement of IVIG therapy at a dose between 0.2 to 0.8 g/kg
and at administration interval of 3-weeks or 4-weeks may be
considered medically necessary for the treatment of the patient
condition
5. Patient already under IgG replacement therapy with a stable dosage
and with 3 documented trough levels ³ 4 g/l within 6 months prior to
the introduction of I10E (trough levels should have been performed at
3 to 8 weeks interval between samples or naïve. All these patients
must be stabilized under I10E during the first 6 months during the
study with IgG trough levels ³ 6 g/L).
6. Written informed consent obtained prior to any study-related
procedure and study product administration from either the patient or
the patient's legal representative
7. If required by national regulation, registered with a social security or
health insurance system
Are the trial subjects under 18? yes
Number of subjects for this age range: 26
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 34
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion Criteria

1. Patient already under IgG replacement therapy with no 3 documented
trough levels ³ 4 g/l within 6 months prior to the introduction of I10E
or patient with 3 documented Ig G trough level not performed within
defined 3 to 8 weeks interval between samples.
2. Known allergy or history of serious adverse reaction to any IgG
3. Known hypersensitivity to the active substance or to any of the
excipients
4. Patient with known antibodies to IgA
5. Chronic renal insufficiency or creatinine clearance values < 80
ml/min in adult patients (Modified Diet in Renal Disease) or < 60
ml/min in paediatric patients (Schwartz formula)
6. History of cardiac insufficiency (NYHA III/IV), cardiomyopathy,
congestive heart failure, or severe hypertension
7. History of thrombotic episodes (including deep vein thrombosis,
myocardial infarction, cerebrovascular accident, pulmonary
embolism) within the last 12 months
8. Loop diuretic treatment within the last week before inclusion
9. Any additional cause of immunodeficiency, other than a primary
immunodeficiency (as acquired immunodeficiency, neutropenia,
malignancy of lymphoïd cells, allogeneic hematopoïetic stem cell
transplantation)
10. Need of routine premedication by corticosteroid before IgG
infusions
11. Acute infection requiring antibiotics within one week before
inclusion
12. Immunosuppressive agents, including anti-CD20 antibodies, within
the last 6 months
13. Need of therapy with forbidden medication (steroid bolus,
prophylactic antibiotic) that cannot be discontinued during the study
14. Protein-loosing enteropathy characterised by serum protein levels <
60 g/l and serum albumin levels < 30 g/l or nephrotic syndrome
characterised by proteinuria ³ 3.5 g/24 hours, serum protein levels <
60 g/l and serum albumin levels < 30 g/l
15. Any serious medical conditions that would interfere with the
clinical assessment of I10E or prevent the patient to comply with the
protocol requirements
16. Patient known to be infected with hepatitis B virus, hepatitis C virus,
or human immunodeficiency virus.
17. Malignant disease other than a adequately treated basal cell or
squamous cell skin carcinoma or in situ cervix carcinoma
18. Administration of another investigational product within the last
month
19. Exposure to blood products or derivatives other than commercial
IgG, within 3 months prior to inclusion.
20. Pregnant with positive results on a HCG-based pregnancy blood test
(> 12 years) or breastfeeding woman, or woman of childbearing
potential with no effective contraception (injectable, patch or
combined oral estro-progestative or progestative contraceptives,
intra-uterine devices of type 'copper T' and levonorgest releasing IU
systems, depot intramuscular medroxyprogesteron, subcutaneous
implants of progestative contraceptives implants).
21. Blood levels of total bilirubin > 2 x upper limit of normal range,
alanine aminotransferase (ALT) or aspartate amino transferase (AST)
> 3 x upper limit of normal range.
22. Anticipated poor compliance of patient with study procedures

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of I10E in preventing acute serious bacterial infections;Secondary Objective: To assess the safety, efficacy, pharmacokinetic of I10E;Primary end point(s): The primary endpoint is the number of acute serious bacterial infections<br>(aSBI) per patient and per year (annualized rate) as defined by the FDA<br>guidance 70 FR 72124 and evaluated by the DSMB:<br>• bacteraemia or sepsis,<br>• bacterial meningitis,<br>• osteomyelitis / septic arthritis,<br>• bacterial pneumonia,<br>• visceral abscess.;Timepoint(s) of evaluation of this end point: see protocol