E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Replacement therapy in patients with primary immunodeficiency disease (PID) |
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E.1.1.1 | Medical condition in easily understood language |
Replacement therapy in patients in which the body does not produce enough of the protein called immunoglobulins or antibodies |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064859 |
E.1.2 | Term | Primary immunodeficiency syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 this study is to demonstrate that the rate of acute serious bacterial infections (i.e., the mean number of acute serious bacterial infections per subject year) is less than 1.0 to provide substantial evidence of efficacy. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study, in addition to further efficacy assessments, are to evaluate the safety and pharmacokinetic characteristics of BT595. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a) Written informed consent/assent obtained from subjects/subjects’ parent(s) or legally acceptable representative indicating that they understand the purpose of and procedures required for the study and are willing to participate in it. b) Male or female, aged 2 through 75 years. c) Diagnosis of PID with impaired antibody production, i.e.: - Diagnosis of common variable immunodeficiency (CVID) as defined by the European Society for Immunodeficiencies (ESID)/Pan American Group for Immunodeficiency (PAGID) diagnostic criteria. Or - X linked agammaglobulinemia (XLA) as defined by ESID/PAGID diagnostic criteria. d) Established replacement therapy with any intravenous immunoglobulin (IVIg) reference preparation during the previous 6 months, including documentation of immunoglobulin G (IgG) trough levels. e) Established replacement therapy with a single IVIg reference preparation for at least 3 months prior to treatment start with BT595 at a 3 or 4 week schedule with a constant IVIg dose that did not change by ±20% of the mean dose, regular dosage intervals, and at least 1 IgG trough level of ≥5 g/L during the previous 3 months.
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E.4 | Principal exclusion criteria |
a) Pregnancy or unreliable contraceptive measures or lactation period (females only). b) Known intolerance to immunoglobulins or comparable substances (e.g., vaccination reaction). c) Known intolerance to proteins of human origin or known allergic reactions to components of the study product. d) Participation in another clinical study within 30 days before entering the study or during the study and/or previous participation in this study. e) Employee or direct relative of an employee of the Contract Research Organization, the study site, or Biotest. f) Acquired medical conditions known to cause secondary immune deficiency, such as chronic lymphatic leukemia, lymphoma, multiple myeloma, as well as protein losing enteropathies and hypoalbuminemia. g) Other medical condition, laboratory finding, or physical examination finding that precludes participation. h) Recent febrile illness that precludes or delays participation. i) Active infection and receiving antibiotic therapy for the treatment of this infection at the time of screening. Note: if the subject is deemed to be a screen failure due to a nonserious active infection requiring antibiotic therapy, the subject may be rescreened after the initial screening. j) Therapy with systemic steroids or other immunosuppressant drugs at the time of enrollment (current daily use of corticosteroids, i.e., >10 mg prednisone equivalent/day for >30 days. Intermittent corticosteroid use during the study is allowable, if medically necessary). k) History of thrombotic events (including myocardial infarction, cerebral vascular accident [including stroke], pulmonary embolism, and deep vein thrombosis) within the 6 months before treatment start with BT595 or the presence of significant risk factors for thrombotic events. l) Therapy with live attenuated virus vaccines within 3 months before start of the study. m) Selective, absolute immunoglobulin A (IgA) deficiency or known antibodies to IgA. n) Positive diagnosis of hepatitis B or hepatitis C. o) Positive HIV test. p) History of drug or alcohol abuse within the 12 months before treatment start with BT595. q) Inability or lacking motivation to participate in the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Rate of acute serious bacterial infections (i.e., the mean number of acute serious bacterial infections per subject year). Acute serious bacterial infections include: • Bacteremia or sepsis • Bacterial meningitis • Osteomyelitis/septic arthritis • Bacterial pneumonia • Visceral abscess
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after 12 months/per subject |
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E.5.2 | Secondary end point(s) |
• IgG trough levels (total IgG) before each infusion • Rate of any infections (number per year) • Rate of nonserious infections (number per year) • Time to resolution of infections • Antibiotic treatment (number of days antibiotic treatment received per month) • Rate of time lost from school/work due to infections (number of days per month) and their treatment (number of days treatment per month) • Hospitalization (number of days per month overall and due to infection) • Fever episodes (number of days per year) • Changes in health-related quality of life: Pediatric subjects (2 17 years, inclusive) will complete the Pediatric Quality of Life (Peds QL™) Measurement Model (child self report and/or parent proxy report). Additionally, all adult subjects will complete the EuroQol Five Dimension (EQ 5D 3L™) Health Questionnaire and pediatric subjects (4 17 years, inclusive) will complete the youth version of the EQ 5D™ (EQ 5D Y™) Health Questionnaire (child self report or proxy report).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
after 12 months/per subject |
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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 | 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 | 11 |
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 |
Russian Federation |
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 | |
E.8.9.1 | In the Member State concerned months | 37 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 37 |