Primary Immunodeficiency Diseases MedDRA version: 20.0 Level: PT Classification code 10064859 Term: Primary immunodeficiency syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Octapharma Pharmazeutika Prod.Ges.m.b.H
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: 1. Age of =2 years and =75 years (1) 2. Documented and confirmed diagnosis of PID as defined by European Society of Immunodeficiencies (ESID) and the Pan American Group for Immune Deficiency (PAGID) and requiring immunoglobulin replacement therapy due to hypogammaglobulinaemia or agammaglobulinaemia. The exact type of PID must be recorded. 3. At least 12 weeks of regular treatment before the screening visit (i.e., with a stable dosing interval) with any IVIG, SCIG, or fSCIG, with a stable IgG dose between 200 and 800 mg/kg/month. A stable dose is defined as one that deviates less than ±25% from the mean dose for all infusions within this 12 week period before screening. 4. Trough level of IgG =5 g/L at screening and documentation of an IgG trough level of =5 g/L at least once within the previous 12 weeks. 5. Freely given written informed consent from adult patients or freely given written informed consent from the patient’s parent(s)/legal guardian(s) and written informed assent from paediatric or adolescent patients in accordance with the applicable regulatory requirements, before any study-specific procedure takes place. 6. Willingness to comply with all aspects of the protocol, including blood sampling, for the duration of the study. ( 1) Only patients 18 years and older with primary immunodeficiency will participate at sites in Czech Republic and the Russian Federation Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Any acute infection requiring IV antibiotic treatment within 2 weeks before the screening visit or during the screening period, or any SBI within the 3 months prior to the screening visit or during the screening period. 2. Patient has isolated specific antibody deficiency disorder, isolated IgG subclass deficiency, or transient hypogammaglobulinaemia of infancy. 3. Current medical condition or history of condition known to cause secondary immune deficiency, for example, chronic lymphocytic leukaemia, lymphoma, multiple myeloma, or chronic or recurrent neutropenia (absolute neutrophil count 40 kg/m2. 6. Exposure to blood or any blood product or plasma derivative other than IgG for PID within 3 months before the first infusion of Newnorm. 7. History of or ongoing severe hypersensitivity, e.g., anaphylaxis or severe systemic response, or persistent reactions to blood or plasma-derived products, or to any component of Newnorm 8. Severe liver dysfunction (alanine aminotransferase [ALT] >3 times the upper limit of normal for the expected normal range for the testing laboratory) at screening. 9. Known protein-losing enteropathies or proteinuria (known urinary protein loss of >1 g/24 h, or dipstick proteinuria of =3+). 10. Moderate to severe renal dysfunction (per investigator discretion based on estimated glomerular filtration rate [eGFR] =44 mL/min/1.73 m2, as defined by KDIGO Clinical Practice Guideline) or predisposition to acute renal failure (e.g., any degree of pre-existing renal dysfunction in presence of additional acute renal failure risk factors, e.g. routine treatment with known nephrotoxic drugs). 11. Uncontrolled diabetes mellitus (HbA1c > 7% / >53 mmol/mol). 12.Uncontrolled arterial hypertension (systolic blood pressure of = 130 mmHg for the subject under 13 years of age, = 140 mmHg for subject 13 to 17 years of age, and > 160 mmHg for adults). 13. Dysrhythmia/Tachycardia (resting heart rate > 100 bpm for adults/adolescents and > 120 bpm for children) and symptomatic bradycardia (resting heart rate 0.3 mg/kg of prednisone (or equivalent) within the last 12 weeks before screening or b. bolus treatment of a daily dose greater than 1 mg/kg of prednisone (or equivalent) for longer than 10 days within the last 12 weeks before screening. Courses of corticosteroids (intermittent) of not more than 10 days would not exclude a patient. Inhaled or topical corticosteroids are allowed. 17. Treatmen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: The primary efficacy objective of this study is to assess the efficacy of Newnorm in preventing serious bacterial infections (SBIs). The primary pharmacokinetic (PK) objective is to confirm that weekly subcutaneous (SC) dosing of Newnorm—adjusted by a dose conversion factor (DCF) of 1.37 for patients previously treated with an intravenous immunoglobulin (IVIG) product—results in average total immunoglobulin G (IgG) levels that are statistically non-inferior to 3- or 4-weekly IVIG dosing. ;Secondary Objective: The secondary objectives of this study are to: - Assess the efficacy of Newnorm in infection control by comparing the rates of any type of infection, the time to resolution, the use of antibiotics, hospitalisations, episodes of fever, and days lost form work, school, kindergarten, or day care with historical data - Assess the effect of Newnorm on quality of life (QoL) - Evaluate the tolerability and safety of Newnorm The secondary PK objectives of this study are to: - Describe the PK characteristics of Newnorm - Compare the minimum (trough) and maximum (peak) systemic levels on weekly dosing of Newnorm with 3- or 4-weekly IVIG dosing ;Primary end point(s): The primary endpoint of this study is the rate of SBIs (defined as bacteraemia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess) per person-year on treatment. The primary efficacy endpoint will be analysed for the 52-week efficacy period. The primary PK endpoint is the average total IgG concentration (Cav) on steady-state dosing. ;Timepoint(s) of evaluation of this end point: week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints are: - Infections of any type or seriousness (including acute sinusitis, exacerbation of chronic sinusitis, acute otitis media, acute bronchitis, infectious diarrhoea, etc) (total and by category, annual rate) - Time to resolution of infections - Use of antibiotics (number of days on antibiotics and annual rate of treatment episodes) characterised as therapeutic or prophylactic use - Hospitalisations due to infection (number of days and annual rate) - Episodes of fever - Days lost from work, school, kindergarten, or day care due to infection - QoL assessments using the Child Health Questionnaire-Parent Form (CHQ-PF50) for patients <14 years and the SF-36 Health Survey for patients =14 years of age The secondary PK endpoints are: - Non-compartmental PK analyses of all available PK profiles (IVIG and SCIG) for total IgG, IgG subclasses (IgG1, IgG2, IgG3, and IgG4), and antigen-specific antibodies against Haemophilus influenzae B (capsular polysaccharide), Streptococcus pneumoniae (serotypes 4, 6B, 9V, 14, 18C, 19F, 23F), cytomegalovirus (CMV), tetanus, and measles - Trough and peak levels of total IgG and IgG subclasses for weekly Newnorm relative to 3- or 4-weekly IVIG dosing ;Timepoint(s) of evaluation of this end point: week 52 For PK screening visits ( PK1) and week 16 ( PK2) | — |
Countries
Germany, Hungary, Italy, Poland, Russian Federation, Slovakia, Ukraine, United States
Contacts
Public ContactGlobal Clinical Project Manager
Octapharma Pharmazeutika Prod.Ges.m.b.H
Outcome results
None listed