E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Immune Deficiency |
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E.1.1.1 | Medical condition in easily understood language |
Primary immune deficiency is a group of diseases in which part of the body's immune system is missing or functions improperly due to inherited (genetic) defects. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064859 |
E.1.2 | Term | Primary immunodeficiency syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 objective of this study is to assess the efficacy, tolerability, safety and pharmacokinetics of IgPro20 in patients with primary humoral immunodeficiency (PID). |
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E.2.2 | Secondary objectives of the trial |
Pharmacokinetic (PK) parameters were assessed in a sub-group of subjects. |
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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 |
Pharmacokinetic Substudy. The primary objective was to evaluate whether the chosen subcutaneous (SC) dose regimen for IgPro20 was associated with a steady-state area under the concentration-time curve (AUC) for serum immunoglobulin (IgG) that was not inferior to the AUC obtained with the previous intravenous (IV) dose regimen. |
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E.3 | Principal inclusion criteria |
- Male or female aged 2 to 75 years
- Subjects with primary humoral immunodeficiency, namely with a diagnosis of: CVID (Common Variable Immunodeficiency) as defined by PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies) or XLA (X-linked Agammaglobulinemia)
- Written informed consent
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E.4 | Principal exclusion criteria |
- Newly diagnosed PID
- Evidence of an active serious infection at the time of screening (i.e., but not limited to: bacteremia/septicemia, pneumonia, fungal osteomyelitis)
- 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
- Allergic reactions to immunoglobulins or other blood products
- Known antibodies to Immunoglobulin A (IgA)
- The subject is receiving steroids (oral and parenteral, daily ≥ 0.15 mg of prednisone equivalent/kg/day) or other systemic immunosuppressants
- Female who is pregnant, breast feeding or planning a pregnancy during the course of the study
- Participation in a study with an investigational product other than (IVIG) within 1 month prior to enrollment
- A positive result at screening on any of the following viral markers: Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV) and Hepatitis B virus (HBV)
- Aspartate aminotransferase (ASAT) or Alanine aminotransferase (ALAT) concentration > 2.5 times the upper normal limit (UNL)
- Creatinine concentration > 1.5 times the UNL
- Any condition that is likely to interfere with evaluation of the study drug or satisfactory conduct of the trial
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) (MITT Population)
2. Area Under the Concentration-time Curve (AUC) of Total Serum Immunoglobulin G (IgG)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Efficacy period: up to 12 months (week 13 to the completion visit)
2. Measured during a single dosing interval after at least 12 weeks of stable subcutaneous (SC) dosing with IgPro20 treatment |
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E.5.2 | Secondary end point(s) |
1. Annualized Rate of Clinically Documented SBIs (ITT Population)
2. Annualized Rate of Clinically Documented SBIs (PPE Population)
3. Annualized Rate of Infection Episodes
4. Number of Infection Episodes (Serious and Non-serious)
5. Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections
6. Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections
7. Annualized Rate of Hospitalization Due to Infection
8. Number of Days of Hospitalization Due to Infections
9. Use of Antibiotics for Infection Prophylaxis and Treatment
10. Total Serum IgG Trough Levels
11. Maximum Concentration (Cmax) of Total Serum IgG at Steady State
12. Tmax at Steady State |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1: For the duration of the study, up to 15 months
2- 9: Efficacy period: up to 12 months (week 13 to the completion visit)
10: Every 4 weeks, throughout the 12-month efficacy period
11,12: Week 28 ± 1 week of the treatment period |
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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 | Yes |
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 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA 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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The end of the study is defined as the last visit of the last subject participating in the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |