E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
primary immunodeficiency disease (PID) |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049485 |
E.1.2 | Term | Bruton's agammaglobulinemia |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010112 |
E.1.2 | Term | Common variable immunodeficiency |
E.1.2 | System Organ Class | 10021428 - Immune system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the pharmacokinetic (PK) profile of Octagam 5% at steady state on standard prophylactic treatment of Primary Immunodeficiency Disorders (PID). |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of Octagam 5% in preventing serious bacterial infections compared to historical control data.
• To evaluate safety and tolerability of Octagam 5%.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age of >= 18 years and <= 75 years.
2. Primary immunodeficiency syndromes with significant component hypogamma-globulinaemia or antibody deficiency.
3. Previously treated with a commercial IVIG
a) approximately every 21–28 days for at least 6 infusion intervals b) at a constant dose between 200 and 800 mg/kg body weight (+/- 20% of the mean dose for the last 6 infusions).
4. Availability of the IgG trough levels of the 2 previous infusions before enrolment, and maintenance of more than 5.0 g/L in the trough levels of these 2 infusions.
5. Negative result on a pregnancy test for women of childbearing potential and use of a reliable method of contraception for the duration of the study.
6. Freely given written informed consent.
7. Willingness to comply with all aspects of the protocol, including blood sampling, for the duration of the study. |
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E.4 | Principal exclusion criteria |
8. Acute infection requiring intravenous antibiotic treatment within 2 weeks prior to and during the screening period.
9. Known history of adverse reactions to IgA in other products.
10. Exposure to blood or any blood product or derivative, other than commercially available IVIG, within the past 3 months prior to enrolment.
11. Ongoing history of hypersensitivity or persistent reactions to blood or plasma derived products, or any component of the investigational product.
12. Requirement of any routine premedication for IVIG infusion.
13. History of congenital impairment of pulmonary function.
14. Severe liver function impairment
15. Presence of renal function impairment, or predisposition for acute renal failure.
16. History of autoimmune haemolytic anaemia.
17. History of diabetes mellitus.
18. Congestive heart failure NYHA class III or IV.
19. Non-controlled arterial hypertension.
20. History of deep vein thrombosis or thrombotic complications of IVIG therapy.
21. Known HIV, HCV, or HBV infection.
22. Presence of any clinically relevant disease or unstable condition at screening, other than PID, which in the opinion of the Investigator could interfere with the conduct of the study.
23. Treatment with steroids , immunosuppressive or immunomodulatory drugs.
24. Planned vaccination during the study period except for “killed” influenza vaccines (incl. H1N1).
25. Participating in another clinical trial or planned participation in another trial for the duration of this study.
26. Treatment with any investigational agent within 3 months prior to enrolment.
27. Known or suspected to abuse alcohol, drugs, psychotropic agents or other chemicals within the past 12 months prior to enrolment.
28. Pregnant or nursing women.
29. Unable or unwilling to comply with the study protocol. |
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E.5 End points |
E.5.1 | Primary end point(s) |
PK profile of Octagam with respect to total IgG, IgG subclasses (IgG1, IgG2, IgG3, IgG4), and antigen-specific antibodies at steady state on standard prophylactic treatment of PID |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
continuously, see protocol |
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E.5.2 | Secondary end point(s) |
• Trough levels of serum total IgG.
• Rate of serious bacterial infections (defined as bacteraemia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess) per person-year on treatment.
• The occurrence of all infections of any kind or seriousness.
• Non-serious infections (total and by category).
• Time to resolution of infections.
• Use of antibiotics.
• Hospitalisations due to infection.
• Episodes of fever.
• Days missed from school or work due to infections and their treatment.
• Occurrence of AEs.
• Occurrence of temporally associated AEs.
• Proportion of infusions with 1 or more temporally associated AEs.
• AEs by infusion rate.
• Short term tolerance parameters including vital signs (blood pressure, heart rate, temperature, respiratory rate).
• Laboratory parameters (haematology, clinical chemistry, and urinalysis).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
continuously, see protocol |
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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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 | 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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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 |