E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Immunodeficiency Diseases (PID) |
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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 the study is to investigate the safety of Octagam® 10% in replacement therapy in PID and to compare the pharmacokinetic profile of Octagam® 10%with that of the previously used commercial Octagam® 5% (Pharmacokinetic sub-study). Safety outcome parameters will be: • Occurrence of adverse events. • Short term tolerance parameters including vital signs (blood pressure, heart rate, temperature, respiratory rate). • Laboratory parameters (hematology, clinical chemistry, direct Coombs’test, urinalysis) and tests for viral safety. Pharmacokinetic outcome parameters will be the parameter Cmax, Cmin, t ½, Tmax, AUC, volume of distribution, and incremental recovery of serum total IgG; of IgG subclasses (IgG1, IgG2, IgG3, IgG4); of specific antibodies against Haemophilus influenzae, Streptococcus pneumoniae (types 4, 6B, 9V, 14, 18C, 19F, 23F), CMV, VZV, tetanus, measles; and of glucose and maltose. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to investigate the efficacy of Octagam® 10% in replacement therapy in PID by monitoring the rate of occurrence of serious bacterial infections, the rate of other infections, the trough (pre-next-dose) levels of total serum IgG and IgG subclasses (IgG1, IgG2, IgG3, IgG4), the trough (pre-next-dose) levels of selected antigen specific antibodies, use of antibiotics, rate of absence from work/school, number and days of hospitalizations. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria: • Age of ≥ 2 years and ≤ 75 years. • For minor patients, above a minimum weight based on the amount of blood required for testing: per individual, the trial-related blood loss (including any losses in the manoeuvre) should not exceed 3% of the total blood volume during a period of four weeks and should not exceed 1% at any single time (the total volume of blood is estimated at 80 ml/kg body weight). • Confirmed diagnosis of primary immunodeficiency as stated by the World Health Organisation and requiring immunoglobulin replacement therapy due to hypogammaglobulinemia or agammaglobulinemia. The exact type of PID should be recorded. • Previously treated with commercial Octagam 5% every 21-28 days for at least 6 infusion intervals at a constant dose between 200-800 mg/kg body weight • Availability of the IgG trough levels of the two previous infusions before enrollment, and maintenance of at least 5.5 g/L in the trough levels of these two infusions. • Negative result on a pregnancy test (HCG-based assay in blood or urine) forwomen of child-bearing potential and use of a reliable method of contraception for the duration of the study. • For adult patients: freely given written informed consent. For minor patients: freely given written informed consent from both parents/legal guardians and written informed assent from the child/adolescent ≥ 8 years of age, according to his/her age and capacity of understanding. • 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 |
Exclusion criteria: • Acute infection requiring intravenous antibiotic treatment within two weeks before screening. • Known history of adverse reactions to IgA in other products. • Exposure to blood or any blood product or derivative, other than a commercially available Octagam 5%, within the past 3 months. • Ongoing history of hypersensitivity or persistent reactions to blood or plasma derived products, or any component of the investigational product, such as maltose. • Requirement of any routine pre-medication for IGIV infusion. • History of congenital impairment of pulmonary function. • Severe liver function impairment (ALAT 3x > normal value) • Severe renal function impairment (creatinine > 120 μmol/L), or predisposition for acute renal failure (e.g. any degree of pre-existing renal insufficiency or routine treatment with known nephritic drugs). • History of autoimmune haemolytic anemia. • History of diabetes mellitus. • Congestive heart failure NYHA III or IV. • None-controlled arterial hypertension (systolic blood pressure > 160 mm Hg and/or diastolic blood pressure > 90 mm Hg). • History of DVT or thrombotic complications of IGIV therapy. • Known to be infected with HIV, HCV or HBV. • Presence of any clinically relevant disease or unstable condition beside those concerning study indication at screening which in the opinion of the investigator may interfere with the conduct of the study. • Treatment with steroids, immunosuppressive or immunomodulatory drugs. • Planned vaccination during the study period. • Treatment with any investigational agent within the prior 3 months. • Known or suspected to abuse alcohol, drugs, psychotropic agents or other chemicals within the last 12 months. • Pregnant and/or nursing women. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint is the rate of Octagam® 10% infusions with one or more adverse events occurring during or within 72 hours after end of the infusion, including adverse events that are determined not to be product-related. Second primary endpoint is the comparison of the pharmacokinetic profile of Octagam® 10% with that of the previously used commercial Octagam® 5%. |
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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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | Information not present in EudraCT |
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 clinical end of the study is defined as the date when the last study patient completes the study. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
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 | 9 |