E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
PID (Primary Immunodeficiency) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064859 |
E.1.2 | Term | Primary immunodeficiency syndrome |
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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 |
The primary objective of this study is to achieve a sustained total serum IgG trough levels comparable to the previous IgG treatment in the ITT population. This will be evaluated from a descriotive comparison of three trough levels measured during previous treatment prior to the study with six consecutive trough levels measured at a steady period within the study. |
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E.2.2 | Secondary objectives of the trial |
Rate of clinically documented serious bacterial infections (SBIs) in the intention-to-treat (ITT) population; SBIs defined as o Bacterial pneumonia o Bacteremia and septicemia o Osteomyelitis / septic arthritis o Bacterial meningitis o Visceral abscess · Rate of clinically documented SBIs in the per protocol efficacy (PPE) population · Number of infection episodes · The number of days out of work/school/kindergarten/day care or unable to perform normal daily activities due to infections · Number of days of hospitalization due to infections · Use of antibiotics for infection prophylaxis and treatment |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Objectives of the Pharmacokinetic (PK) assesment are evaluations of the parameters AUC, Cmax and Tmax of total IgG, and the serum concentration of IgG subclasses, specific IgGs. In addition L-proline will be measured in the samples taken during the PK assesment. |
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E.3 | Principal inclusion criteria |
· Male or female aged > 24 months and £ 65 years · Subjects with primary humoral immunodeficiency, namely with a diagnosis of o CVID as defined by PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies) o or XLA as defined by PAGID and ESID o or Autosomal Recessive Agammaglobulinemia · Subjects who have received o IVIG therapy at regular 3- or 4-week intervals o or SCIG therapy at regular weekly intervals at a stable dose (variations of ± 10% are allowed) for at least 6 months prior to receiving IgPro20 (maintenance dose to reach a cumulative monthly dose of the order of 0.2 – 0.8 g/kg) · At least 3 documented IgG trough levels of = 5 g/L during 3 months on IVIG or SCIG replacement therapy immediately prior to receiving IgPro20; 2 of the 3 IgG trough levels may go back up to 6 months prior to receiving IgPro20, in case of stable dosing for at least 3 months prior to this assessment · Chest X-ray or CT Scan obtained within 1 year prior to enrollment · Women of childbearing potential using medically approved contraception and having a negative pregnancy test at screening · Written informed consent
Inclusion criteria for PK assessment · Male or female aged = 6 years · Written informed consent |
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E.4 | Principal exclusion criteria |
· Newly diagnosed PID, i.e. subjects who have not previously received immunoglobulin replacement therapy · Ongoing serious bacterial infection at the time of screening · Malignancies of lymphoid cells such as lymphocytic leukemia, Non-Hodgkin’s lymphoma and immunodeficiency with thymoma · Known hyperprolinemia · Hypoalbuminemia, protein- losing enteropathies, and any proteinuria (defined by total urine protein concentration > 0.2 g/L) · Allergic or other severe reactions to immunoglobulins or other blood products associated with high anti-IgA · The subject is receiving steroids (oral and parenteral, daily = 0.15 mg of prednisone equivalent/kg/day) or other systemic immunosuppressants · Females who are pregnant, breast feeding or planning a pregnancy during the course of the study · A positive result at screening on any of the following viral markers: HIV, HCV or HBV · ASAT or ALAT concentration > 2.5 times Upper Limit of Normal Range (ULNR) · Creatinine concentration > 1.5 times ULNR · Participation in a study with an investigational product other than immunoglobulin within 3 months prior to enrollment · Evidence of uncooperative attitude · Any condition that is likely to interfere with evaluation of the study drug or satisfactory conduct of the trial · Patients who are employees at the investigational site, relatives or spouse of the investigator |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary variable of this study is to descriptively compare IgG trough levels at 6 consecutive weeks at steady state within the study, i.e. IgG levels priopr to infusions 12 to 17, with 3 trough levels abtained from the subject's previous treatment during the last 3 to 6 months prior ot the study. |
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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 | No |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 | 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
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |