E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Person with impaired immune system |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
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 first primary objective of the study is to assess the efficacy of octanorm in preventing serious bacterial infections compared with historical control data. The second primary objective is to evaluate the pharmacokinetic (PK) characteristics of octanorm and to compare the area under the curve (AUC) with that of IVIG. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: • To evaluate the tolerability and safety of octanorm. • To determine the PK profile of octanorm. • To assess the dosing conversion factor when switching patients from intravenous immunoglobulin treatment. • To develop guidance and recommendations to support further adjustments of octanorm dosing based on the total IgG trough level. • To assess the effect of octanorm on Quality of Life measures. |
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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 |
Secondary pharmacokinetic endpoints: • PK profiles of total IgG, of IgG subclasses (IgG1, IgG2, IgG3, IgG4), and of antigenspecific antibodies against Haemophilus influenzae, Streptococcus pneumoniae (types 4, 6B, 9V, 14, 18C, 19F, 23F), cytomegalovirus (CMV), tetanus, and measles. • Trough levels of serum total IgG (total and subclasses) throughout the study. • Trough levels of specific antibodies against Haemophilus influenzae, Streptococcus pneumoniae (types 4, 6B, 9V, 14, 18C, 19F, 23F), CMV, tetanus, and measles throughout the study. |
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E.3 | Principal inclusion criteria |
1. Age of ≥2 years and ≤75 years. 2. Confirmed diagnosis of PI as defined by ESID and PAGID and requiring immunoglobulin replacement therapy due to hypogammaglobulinaemia or agammaglobulinaemia. The exact type of PI should be recorded. 3. Patients on regular IVIG treatment for at least 6 infusions at a constant dose between 200 and 800 mg/kg body weight (±20% of the mean dose for the last 6 infusions). For a minimum of at least 2 months prior study entry, patients have to be on the same IVIG brand. 4. Availability of the IgG trough levels of 2 previous IVIG infusions before enrolment, and maintenance of ≥5.0 g/L in the trough levels of these 2 previous infusions. 5. Negative result on a pregnancy test (HCG-based assay in urine) for women of childbearing potential and use of a reliable method of contraception for the duration of the study. 6. For adult patients: freely given written informed consent. For minor patients: freely given written informed consent from parents/legal guardians and written informed assent from the child/adolescent in accordance with the applicable regulatory requirements. 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 |
1.Acute infection requiring intravenous antibiotic treatment within 2 weeks prior to and during the screening period. 2. Known history of adverse reactions to IgA in other products. 3. Patients with body mass index ≥40 kg/m2. 4. Exposure to blood or any blood product or plasma derivatives, other than IVIG treatment for PID, within the past 3 months prior to first infusion of octanorm. 5. Ongoing history of hypersensitivity or persistent reactions to blood or plasma derived products, or any component of the investigational product (such as polysorbate 80). 6. Requirement of any routine premedication for IgG administration. 7. History of malignancies of lymphoid cells and immunodeficiency with lymphoma. 8. Severe liver function impairment (ALAT 3 times above upper limit of normal). 9. Known protein-losing enteropathies or proteinuria. 10. Presence of renal function impairment (creatinine >120 μM/L or creatinine >1,35 mg/dL), or predisposition for acute renal failure (e.g., any degree of pre-existing renal insufficiency or routine treatment with known nephritic drugs). 11. Treatment with oral or parenteral steroids for ≥30 days or when given intermittently or as bolus at daily doses ≥0.15 mg/kg. 12. Treatment with immunosuppressive or immunomodulatory drugs. 13. Live viral vaccination (such as measles, rubella, mumps and varicella) within the last 2 months prior to first infusion of octanorm. 14. Treatment with any investigational medicinal product within 3 months prior to first infusion of octanorm. 15. Presence of any condition, that is likely to interfere with the evaluation of study medication or satisfactory conduct of the trial. 16. Known or suspected to abuse alcohol, drugs, psychotropic agents or other chemicals within the past 12 months prior to first infusion of octanorm. 17. Known or suspected HIV, HCV, or HBV infection. 18. Pregnant or nursing women. 19. Planned pregnancy during course of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the rate of SBI (defined as bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess) per person-year on treatment.
The primary endpoint with respect to the PK investigations is the AUC from time 0 (start of the infusion) to the end of the nominal dosing period, standardized to 1 week (AUCτ), at steady-state conditions. |
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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) |
Secondary efficacy endpoints: • The annual rate of all infections of any kind or seriousness. • Non-serious infections (total and by category). • Time to resolution of infections. • Use of antibiotics (number of days and annual rate). • Hospitalizations due to infection (number of days and annual rate). • Episodes of fever. • Days missed from work/school/kindergarten/day care due to infections and their treatment. • QoL assessments using the CHQ-PF50 from parent or guardian of patients <14 years of age and the SF-36 Health Survey in patients ≥14 years of age.
Secondary pharmacokinetic (PK) endpoints: • PK profiles of total IgG, of IgG subclasses (IgG1, IgG2, IgG3, IgG4), and of antigen-specific antibodies against Haemophilus influenzae, Streptococcus pneumoniae (types 4, 6B, 9V, 14, 18C, 19F, 23F), cytomegalovirus (CMV), tetanus, and measles. • Trough levels of serum total IgG (total and subclasses) throughout the study. • Trough levels of specific antibodies against Haemophilus influenzae, Streptococcus pneumoniae (types 4, 6B, 9V, 14, 18C, 19F, 23F), CMV, tetanus, and measles throughout • IVIG to octanorm DCF (based on the area under the concentration-time curve [AUCτ]).
Secondary safety endpoints: • Occurrence of all treatment emergent adverse events (TEAEs) throughout the entire 65-week treatment period starting with the first infusion of octanorm. • Occurrence of temporally associated TEAEs. • Proportion of infusions with at least 1 temporally associated adverse event (AE). • Occurrence of suspected adverse reactions (SARs). • TEAEs by speed of infusion. • Local injection site reactions. • Vital signs (blood pressure, pulse, body temperature, respiratory rate). • Laboratory parameters (hematology, clinical chemistry, markers for intravascular hemolysis, and tests for viral safety). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | No |
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 |
Canada |
Czech Republic |
Hungary |
Poland |
United States |
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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 | 3 |
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 | 3 |