E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
a primary immunodeficiency as defined by the ESID and validated by a reference centre : • X-linked agammaglobulinemia (XLA) • Autosomal recessive inherited agammaglobulinemia (including autosomal recessive hyper-IgM syndrome) • Common variable immunodeficiency (CVID) • IgG subclass deficiency (at least 2 subclasses) with clinical manifestations of immunodeficiency |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010112 |
E.1.2 | Term | Common variable immunodeficiency |
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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 |
To assess the efficacy of I10E in preventing acute serious bacterial infections |
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E.2.2 | Secondary objectives of the trial |
To assess the safety, efficacy, pharmacokinetic of I10E |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Both genders
2. Age between 2 to 70 year old
3. Has an humoral primary immunodeficiency as defined by the ESID and validated by the reference centers : • X-linked agammaglobulinemia (XLA) • Autosomal recessive inherited agammaglobulinemia (including autosomal recessive hyper-IgM syndrome) • Common variable immunodeficiency (CVID) • IgG subclass deficiency (at least 2 subclasses) with clinical manifestations of immunodeficiency
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 >= 4 g/l within 6 months prior to the introduction of I10E or naïve. All these patients must be stabilized under I10E during the first 6 months during the study with IgG trough levels >= 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 |
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E.4 | Principal exclusion criteria |
1. Patient already under IgG replacement therapy with no 3 documented trough levels >= 4 g/l within 6 months prior to the introduction of I10E
2. Known allergy or history of serious adverse reaction to any IgG
3. Patient with known antibodies to IgA
4. Chronic renal insufficiency or creatinin clearance values < 80 ml/min in adult patients (Modified Diet in Renal Disease) or < 60 ml/min in paediatric patients (Schwartz formula)
5. History of cardiac insufficiency (NYHA III/IV), cardiomyopathy, congestive heart failure, or severe hypertension
6. History of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) within the last 12 months
7. Loop diuretic treatment within the last week before inclusion
8. Any additional cause of immunodeficiency, other than a primary immunodeficiency (as acquired immunodeficiency, lymphocytopenia, neutropenia, malignancy of lymphoïd cells, allogeneic hematopoïetic stem cell transplantation)
9. Need of routine premedication by steroid before IgG infusionsinfusions
10. Acute infection requiring antibiotics within one week before inclusion
11. Immunosuppressive agents, including anti-CD20 antibodies, within the last 6 months
12. Need of therapy with forbidden medication (steroid bolus, prophylactic antibiotic) that cannot be discontinued during the study
13. Protein-loosing enteropathy characterised by serum protein levels < 60 g/l and serum albumin levels < 30 g/l or nephrotic syndrome characterised by proteinuria >= 3.5 g/24 hours, serum protein levels < 60 g/l and serum albumin levels < 30 g/l
14. Any serious medical conditions that would interfere with the clinical assessment of I10E or prevent the patient to comply with the protocol requirements
15. Patient known to be infected with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus.
16. Malignant disease other than a adequately treated basal cell or squamous cell skin carcinoma or in situ cervix carcinoma
17. Administration of another investigational product within the last month
18. Exposure to blood products or derivatives other than commercial IgG, within 3 months prior to inclusion.
19. 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).
20. 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.
21. Anticipated poor compliance of patient with study procedures |
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E.5 End points |
E.5.1 | 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.
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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 | No |
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 | No |
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 | No |
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.8.3 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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End of the study will be last patient last visit |
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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |