E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Immunodeficiency Disease (PIDD) |
Elsődleges immunhiányos betegségek |
|
E.1.1.1 | Medical condition in easily understood language |
Conditions due to defects of the immune system |
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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 | 20.0 |
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 |
Safety of HyQvia treatment in pediatric subjects with PIDD who have received prior immunoglobulin therapy before enrollment into the study. |
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E.2.2 | Secondary objectives of the trial |
Further safety assessments (e.g. immunogenicity), tolerability, characteristic of product administration and efficacy (immunoglobulin G [IgG] trough levels). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject must have a documented diagnosis of a form of primary humoral immunodeficiency involving a defect in antibody formation and requiring
gammaglobulin replacement, as defined according to the IUIS (International Union of Immunological Societies) Scientific Committee 2015 1 prior to enrollment. The diagnosis must be confirmed by the sponsor Medical Director prior to first treatment with IP in the study.
2. Subject is at least two and below 18 years of age at the time of screening.
3. Subject has been receiving a consistent dose of IgG, administered in compliance with the respective product information for a period of at least three months prior to screening. The average minimum pre-study dose over that interval was equivalent to 300 mg/kg BW/four weeks and a maximum dose equivalent to 1000 mg/kg BW/4 weeks.
4. Subject has a serum trough level of IgG > 5 g/L at screening.
5. If female of childbearing potential, subject presents with a negative pregnancy test and agrees to employ adequate birth control measures for the duration of the study.
6. Subject/legally authorized representative is willing and able to comply with the requirements of the protocol. |
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E.4 | Principal exclusion criteria |
1. Subject has a known history of or is positive at screening for one or more of the following: hepatitis B surface antigen (HBsAg), polymerase chain reaction (PCR) for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1/2.
2. Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent):
a. Persistent alanine aminotransferase (ALT) and aspartate amino transferase (AST) >2.5 times the upper limit of normal (ULN) for the testing laboratory b. Persistent severe neutropenia (defined as an absolute neutrophil count [ANC] ≤ 500/mm3)
3. Subject has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site.
4. Subject has an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IV immunoglobulin, SC immunoglobulin, and/or Immune Serum Globulin (ISG) infusions.
5. Subject has severe immunoglobulin A (IgA) deficiency (less than 7.0 mg/dL) with known anti-IgA antibodies and a history of hypersensitivity. .
6. Subject has a known allergy to hyaluronidase.
7. Subject has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening.
8. Subject has a bleeding disorder or a platelet count less than 20,000/μL, or who, in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of SC therapy.
9. Subject has severe dermatitis that would preclude adequate sites for safe product administration in the opinion of the investigator.
10. Subject has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to
participate in another clinical study involving an IP or investigational device during the course of this study.
11. Subject is a family member or employee of the investigator.
12. If female, subject is pregnant or lactating at the time of enrollment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number and rate per infusion (excluding infections) of all severe related AEs
Number and rate per infusion (excluding infections) of related SAEs |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Efficacy: Trough levels of IgG (for Study Epoch 1 and 2)
Safety/Tolerability:
Proportion of subjects who achieve a treatment interval of three or four weeks in Epoch 2
Proportion of subjects who maintain a treatment interval of three or four weeks in Epoch 2 for 12 months
Number and rate per infusion (excluding infections) of local AEs and ARs
Number and rate per infusion (excluding infections) of systemic AEs and ARs
Number and rate per infusion (excluding infections) of all AEs and all ARs
Number and rate per infusion (excluding infections) of all temporally associated AEs
Number and rate per infusion (excluding infections) of all causally related and/or temporally associated AEs
Number and rate per infusion (excluding infections) of all SAEs
Number/proportion of subjects who develop positive titer (≥160) of binding or neutralizing antibodies to rHuPH20 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy: Up to three years.
Safety: Up to one year. |
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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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 |
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 | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
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 |