E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary immunodeficiency diseases |
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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 |
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.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) |
The secondary endpoints are:
Efficacy:
• Trough levels of serum total IgG.
• Trough levels of specific antibodies against Haemophilus influenzae, Streptococcus pneumoniae, CMV, VZV, tetanus, measles.
• 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.
• Hospitalizations due to infection.
• Episodes of fever.
• Days missed from school or work due to infections and their treatment.
• QoL assessments.
For PK:
PK profiles of total IgG, IgG subclasses and antigenspecific antibodies
For Safety:
• Occurrence of AEs and temporally TAAEs
• Proportion of infusions with TAAEs
• AEs by infusion rate
• Short term tolerance parameters
• Laboratory parameters
• Physical examination |
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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) | 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 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA 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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E.8.9 Initial estimate of the duration of the trial |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |