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

• Register: EUCTR
• Last refreshed on: 27 May 2013
• Main ID: EUCTR2010-023483-41-HU
• Date of registration: 10/11/2010
• Prospective Registration: Yes
• Primary sponsor: LFB BIOTECHNOLOGIES
• Public title: 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
• Scientific title: A MULTICENTER STUDY ON THE EFFICACY, SAFETY AND PHARMACOKINETICS OF I10E IN PATIENTS WITH PRIMARY IMMUNODEFICIENCY (PID) - I10E-0718
• Date of first enrolment: 01/03/2011
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-023483-41
• 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: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1

Countries of recruitment

Czech Republic, France, Hungary, Lithuania, Poland, Serbia, Ukraine

Contacts

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

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

Key inclusion & exclusion criteria

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:
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


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

Health Condition(s) or Problem(s) studied

a primary immunodeficiency as defined by the ESID and validated by a reference centre : • X-linked agammaglobulinemia (XLA) • Common variable immunodeficiency (CVID)
MedDRA version: 14.1 Level: LLT Classification code 10010112 Term: Common variable immunodeficiency System Organ Class: 100000004870
MedDRA version: 14.1 Level: HLT Classification code 10036700 Term: Primary immunodeficiency syndromes System Organ Class: 100000004870
MedDRA version: 14.1 Level: LLT Classification code 10001471 Term: Agammaglobulinemia System Organ Class: 100000004870

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: HUMAN NORMAL IMMUNOGLOBULIN FOR
Product Code: I10E
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: HUMAN NORMAL IMMUNOGLOBULIN FOR INTRAVENOUS USE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Main Objective: To assess the efficacy of I10E in preventing acute serious bacterial infections

Timepoint(s) of evaluation of this end point: see protocol

Primary end point(s): The primary endpoint is the number of acute serious bacterial infections
(aSBI) per patient and per year (annualized rate) as defined by the FDA
guidance 70 FR 72124 and evaluated by the DSMB:
• bacteraemia or sepsis,
• bacterial meningitis,
• osteomyelitis / septic arthritis,
• bacterial pneumonia,
• visceral abscess.

Secondary Objective: To assess the safety, efficacy, pharmacokinetic of I10E

Secondary Outcome(s)

Secondary end point(s): 1) Efficacy criteria
Serum total IgG trough levels:
• Total IgG trough concentrations will be measured by nephelemetry
(central lab) in serum obtained from blood samples collected prior to
each infusion from all included patients during the 12 month-study
period. In addition, distribution of IgG sub-classes and content of
clinically relevant antibodies will be assessed.
• Descriptive relationship between total IgG trough levels and serious
all infections.
Other efficacy criteria will be assessed both by investigator and patients
follow-up diaries (annualized rate) :
• Number of all infections per patient and per year: annualized rate of
documented of serious and non-serious bacterial infections
• Number of days missed from work or school due to infections,
• Number of days hospitalized related to infections,
• Number of days with use of antibiotics related to infections,
• Number of fever episodes related to infections
2) Safety criteria
Adverse events (AEs), serious (SAEs) and non serious adverse events
from all subjects followed throughout the clinical studies will be
recorded and reported regardless of whether the AE is determined to
be related to the product or not by the investigator (Pre-medication is
discouraged to avoid masking AEs).
Safety evaluation will include the monitoring of the following items:
• Vital signs (blood pressure, heart rate, temperature) will be
monitored by the study nurse during infusions within 30 mn
after the end of the infusion
• Laboratory tests including direct Coombs' test will be
monitored at each visit
• Adverse events that occurred during infusions will be noted
by the study nurse or the investigator
• Adverse events that occurred during intervals between
infusions will be recorded by the patients in their diaries and
reviewed by the investigator at each visit.
• Renal function, hepatic function and blood cells will be
monitored by biological tests.
3) Pharmacokinetics (PK)

Timepoint(s) of evaluation of this end point: see protocol

Secondary ID(s)

I10E-0718

Source(s) of Monetary Support

LFB BIOTECHNOLOGIES