E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary immunodeficiency diseases |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010112 |
E.1.2 | Term | Common variable immunodeficiency |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10049485 |
E.1.2 | Term | Bruton's agammaglobulinemia |
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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 assess the efficacy of NewGam in preventing serious bacterial infections compared to historical control data. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: • To evaluate the safety of NewGam. • To determine the PK profile of NewGam. • To assess the effect of NewGam on QoL measures. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients who meet the following criteria can be included: 1. Age of ≥ 2 years and ≤ 75 years. 2. 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 maneuver) should not exceed 3% of the total blood volume during a period of 4 weeks and should not exceed 1% at any single time (the total volume of blood is estimated at 80 mL/kg body weight). 3. Confirmed diagnosis of CVID or XLA. 4. Previously treated with a commercial immune globulin intravenous (human) a) every 21–28 days for at least 6 infusion intervals (± 3 days for the last three infusions and ± 7 days for the three infusions before the last three infusions) b) at a constant dose between 200 and 800 mg/kg body weight (± 20% of the mean dose for the last 6 infusions). 5. Availability of the IgG trough levels of the 2 previous infusions before enrollment, and maintenance of at least 5.5 g/L in the trough levels of these 2 infusions. 6. 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. 7. 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 approvals. 8. 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. Exposure to blood or any blood product or derivative, other than commercially available IVIG, within the past 3 months prior to enrollment. 4. Ongoing history of hypersensitivity or persistent reactions to blood or plasma derived products, or any component of the investigational product. 5. Requirement of any routine premedication for IVIG infusion. 6. History of congenital impairment of pulmonary function. 7. Severe liver function impairment (ALAT 3x > upper limit of normal). 8. Presence of renal function impairment (creatinine > 120 micromol/L), or predisposition for acute renal failure (e.g. any degree of pre-existing renal insufficiency or routine treatment with known nephritic drugs). 9. History of autoimmune hemolytic anemia. 10. History of diabetes mellitus. 11. Congestive heart failure NYHA class III or IV. 12. Non-controlled arterial hypertension (systolic blood pressure > 160 mmHg or diastolic blood pressure > 90 mmHg). 13. History of deep vein thrombosis or thrombotic complications of IVIG therapy. 14. A positive result at screening on any of the following viral markers: HIV, HCV, HBV. 15. 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. 16. Treatment with steroids (oral or parenteral, long-term, i.e. 30 days or more, not intermittent or burst, daily, ≥ 0.15 mg of prednisone or equivalent/kg/day), immunosuppressive or immunomodulatory drugs. 17. Planned vaccination during the study period. 18. Treatment with any investigational agent within 3 months prior to enrollment. 19. Known or suspected to abuse alcohol, drugs, psychotropic agents or other chemicals within the past 12 months prior to enrollment. 20. Pregnant or nursing women.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the rate of serious bacterial infections (defined as bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess) per person-year on treatment. |
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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 | 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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | Information not present in EudraCT |
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 |
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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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The clinical end of the study is defined as the date when the last study patient completes the study. Three or 4 weeks (according to the treatment schedule) after the last infusion, or sooner if a patient withdraws from the study, a follow-up visit will be performed. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 21 |
E.8.9.2 | In all countries concerned by the trial days | 0 |