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 sustained total serum IgG trough levels comparable to the previous IgG treatment in the ITT population. This will be evaluated from a descriptive comparison of three trough levels measured during previous treatment prior to the study with six consecutive trough levels measured at a steady state period within the study. |
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E.2.2 | Secondary objectives of the trial |
Secondary efficacy objectives of the study are the rate of clinically documented serious bacterial infections, the 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, the number of days of hospitalization due to infections, and the use of antibiotics for infection prophylaxis and treatment. Safety objectives of this study are monitoring of short-term tolerance (blood pressure, heart rate, body temperature), the local tolerability of subcutaneous infusions, monitoring of adverse events, vital sign changes before and after infusions at the study site, and changes in routine laboratory parameters as compared to baseline assessments.
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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 PK substudy are to determine the PK parameters AUC, Cmax and Tmax of total IgG as well as serum concentrations of IgG subclasses and specific IgGs. In addition, L-proline will be measured in the samples taken during the PK assessment. |
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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 - CVID as defined by PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies (16)) - or XLA as defined by PAGID and ESID (16) - or Autosomal Recessive Agammaglobulinemia · Subjects who have received - IVIG therapy at regular 3- or 4-week intervals - 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 SUBSTUDY · 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 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 prior to infusions 12 to 17, with 3 trough levels obtained from the subject’s previous treatment during the last 3 to 6 months prior to 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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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
| 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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
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 | 11 |