CLINICAL PHASE III STUDY TO MONITOR THE SAFETY, TOLERABILITY AND EFFICACY OF SUBCUTANEOUS HUMAN IMMUNOGLOBULIN (OCTANORM) IN PATIENTS WITH PRIMARY IMMUNODEFICIENCY DISEASES, INCLUDING (BUT NOT LIMITED TO) THOSE WHO HAVE COMPLETED THE SCGAM-01 TRIAL

Study Overview
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Brief Summary
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Summary for SCGAM-03: Clinical phase III study to monitor the safety, tolerability and efficacy of subcutaneous human immunoglobulin (Octanorm) in patients with primary immunodeficiency diseases who have completed the SCGAM-01 trial. Summary for SCGAM-03 in Canada: Clinical phase III study to monitor the safety, tolerability and efficacy of subcutaneous human immunoglobulin (octanorm) in patients with primary immunodeficiency diseases, including (but not limited to) those who have completed the SCGAM-01 trial

Official Title
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Title for SCGAM-03: CLINICAL PHASE III STUDY TO MONITOR THE SAFETY, TOLERABILITY AND EFFICACY OF SUBCUTANEOUS HUMAN IMMUNOGLOBULIN (OCTANORM) IN PATIENTS WITH PRIMARY IMMUNODEFICIENCY DISEASES WHO HAVE COMPLETED THE SCGAM-01 TRIAL Title for SCGAM-03 in Canada: CLINICAL PHASE III STUDY TO MONITOR THE SAFETY, TOLERABILITY AND EFFICACY OF SUBCUTANEOUS HUMAN IMMUNOGLOBULIN (OCTANORM) IN PATIENTS WITH PRIMARY IMMUNODEFICIENCY DISEASES, INCLUDING (BUT NOT LIMITED TO) THOSE WHO HAVE COMPLETED THE SCGAM-01 TRIAL

Conditions
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Primary Immunodeficiency

Intervention / Treatment
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* Drug: Octanorm 16.5%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for SCGAM-03: Completion of the main study SCGAM-01, with good tolerance of Octanorm (as determined by the investigator). For adult patients: freely given written informed consent. For patients below the legal age of majority: freely given written informed consent from parents/legal guardians and written informed assent from the child/adolescent in accordance with local requirements. For female patients of child-bearing potential, a negative result in a urine pregnancy test conducted at the Screening visit. Willingness to comply with all aspects of the protocol, including blood sampling, for the duration of the study. Inclusion Criteria for SCGAM-03 in Canada: Either: SCGAM-01 patients (United States, Canada): 1. Completion of the main study SCGAM-01, with good tolerance of octanorm (as determined by the investigator). Or: De novo patients (Canada only): C-a Age of ≥18 years and ≤75 years. 1C-b Confirmed diagnosis of PI as defined by ESID and PAGID and requiring immunoglobulin replacement therapy due to hypogammaglobulinaemia or agammaglobulinaemia. The exact type of PI should be recorded. C-c Availability of the IgG trough levels of 2 previous SCIG infusions before enrolment, and maintenance of ≥5.0 g/L in the trough levels of these 2 previous infusions. And: 2. For adult patients: freely given written informed consent. For patients below the legal age of majority: freely given written informed consent from parents/legal guardians and written informed assent from the child/adolescent in accordance with local requirements. 3. For female patients of child-bearing potential, a negative result in a urine pregnancy test conducted at the Screening Visit. 4. Willingness to comply with all aspects of the protocol, including blood sampling, for the duration of the study. Exclusion Criteria for SCGAM-03: Subject being without any IgG treatment for period greater than approximately 5 weeks between the last infusion of Octanorm in the SCGAM-01 study and the first infusion of Octanorm in the SCGAM-03 study. Exposure to blood or any blood product or derivative, other than IgG used for regular PID treatment, within the 3 months before the first infusion in this study. Planned pregnancy during the course of the study. Exclusion Criteria for SCGAM-03 in Canada: Either: SCGAM-01 patients (United States, Canada): 1 Subject being without any IgG treatment for period greater than 5 weeks between the last infusion of octanorm in the SCGAM-01 study and the first infusion of octanorm in the SCGAM-03 study. Or: De novo patients (Canada only): 1C-a Acute infection requiring intravenous antibiotic treatment within 2 weeks prior to and during the screening period. 1C-b Known history of adverse reactions to IgA in other products. 1C-c Patients with body mass index >40 kg/m2. 1C-d Ongoing history of hypersensitivity or persistent reactions to blood or plasma derived products, or any component of the investigational product (such as Polysorbate 80). 1C-e Requirement of any routine premedication for IgG administration. 1C-f History of malignancies of lymphoid cells and immunodeficiency with lymphoma. 1C-g Severe liver function impairment (ALAT 3 times above upper limit of normal). 1C-h Known protein-losing enteropathies or proteinuria. 1C-i Presence of renal function impairment (creatinine >120 μM/L or creatinine >1.35 mg/dL), or predisposition for acute renal failure (e.g., any degree of pre-existing renal insufficiency or routine treatment with known nephritic drugs). 1C-j Treatment with oral or parenteral steroids for ≥30 days or when given intermittently or as bolus at daily doses ≥0.15 mg/kg. 1C-k Treatment with immunosuppressive or immunomodulatory drugs. 1C-l Live viral vaccination (such as measles, rubella, mumps and varicella) within the last 2 months prior to first infusion of octanorm. And: 2. Exposure to blood or any blood product or plasma derivatives, other than SCIG used for regular PID treatment, within the 3 months before the first infusion of octanorm in this study. 3. Pregnant or nursing women or planned pregnancy during the course of the study. 4. Treatment with any investigational medicinal product (other than that of SCGAM-01) within 3 months prior to first infusion of octanorm. 5. Presence of any condition, that is likely to interfere with the evaluation of study medication or satisfactory conduct of the trial. 6. Known or suspected to abuse alcohol, drugs, psychotropic agents or other chemicals within the past 12 months prior to first infusion of octanorm. 7. Known or suspected HIV, HCV, or HBV infection.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Octanorm 16.5%<br>octanorm 16.5%, human normal immunoglobulin for subcutaneous (SC) administration. | Drug: Octanorm 16.5%<br>* Human normal immunoglobulin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of All Treatment-emergent Adverse Events (TEAEs) | Number of TEAEs | From study start to end, up to 3.5 years | 
| Occurrence of Temporally Associated TEAEs |  | From study start to end, up to 3.5 years | 
| Number of Temporally Associated TEAEs by Infusion Rate | Number of temporally associated TEAEs by infusion rate. Only includes systemic TEAEs without infections and without infusion site reactions | From study start to end, up to 3.5 years | 
| Local Injection-site Reactions |  | From study start to end, up to 3.5 years | 
| Blood Pressure | Systolic and diastolic. | From study start to end, up to 3.5 years | 
| Body Temperature |  | From study start to end, up to 3.5 years | 
| Respiratory Rate |  | From study start to end, up to 3.5 years | 
| Sodium | Changes in sodium levels from baseline to end of study | From study start to end, up to 3.5 years | 
| Potassium | Changes in potassium levels from baseline to end of study | From study start to end, up to 3.5 years | 
| Blood Glucose | Changes in blood glucose from baseline to end of study | From study start to end, up to 3.5 years | 
| ALAT | Changes in ALAT (alanine transaminase) from baseline to end of study | From study start to end, up to 3.5 years | 
| ASAT | Changes in ASAT (aspartate aminotransferase) from baseline to end of study | From study start to end, up to 3.5 years | 
| LDH | Changes in LDH (lactate dehydrogenase) from baseline to end of study | From study start to end, up to 3.5 years | 
| Total Bilirubin | Changes in total bilirubin from baseline to end of study | From study start to end, up to 3.5 years | 
| Blood Urea Nitrogen | Changes in blood urea nitrogen from baseline to end of study | From study start to end, up to 3.5 years | 
| Creatinine | Changes in creatinine from baseline to end of study | From study start to end, up to 3.5 years | 
| Urine pH | Changes in urine pH from baseline to end of study | From study start to end, up to 3.5 years | 
| Number of Participants With a Change in Urine Glucose | Number of Participants with a Change in Urine Glucose | From study start to end, up to 3.5 years | 
| Number of Participants With a Change in Urine Ketones | Number of Participants With a Change in Urine Ketones at baseline and end of study | From study start to end, up to 3.5 years | 
| Number of Participants With a Change in Urine Leukocytes | Number of participants with a change in urine leukocytes at baseline and end of study | From study start to end, up to 3.5 years | 
| Number of Participants With a Change in Urine Hemoglobin | Number of participants with a change in urine hemoglobin at baseline and end of study | From study start to end, up to 3.5 years | 
| Complete Red Blood Cell Count | Changes in complete red blood cell count from baseline to end of study | From study start to end, up to 3.5 years | 
| Haematocrit | Changes in haematocrit from baseline to end of study | From study start to end, up to 3.5 years | 
| Haemoglobin | Changes in haemoglobin from baseline to end of study | From study start to end, up to 3.5 years | 
| Complete White Blood Cell Count | Changes in complete white blood cell count from baseline to end of study | From study start to end, up to 3.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SF-36 Health Survey. | Quality of Life for patients >= age 14 assessed using the Short Form 36 Health survey. Likert like scale. The responses given by patients were combined to create 8 SF-36 scores: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, mental health 36 questions that fall into 4 Sub scale scoring ranges: Score 1-5: Where 1 is more favorable than 5 Score 1-3: Where 3 is more favorable than 1 Score 1-5: Where 5 is more favorable than 1 Score 1-6: Where 1 is more favorable than 6 The raw subscale scores are converted into a scale score between 0 to 100 using the Quality Metric Health Outcomes™ Scoring Software 2.0 Scale Title of final scales is: Physical and Mental Health Component Summary Scores Range: Lowest = 0 and highest = 100 where a high score equates to a more favorable health state | From study start to end, up to 3.5 years | 
| CHQ-PF50 (Child Health Questionnaire-Parent Form) | Quality of Life for patients ages <14 years assessed using the CHQ-PF50. Measured values represent change in score from baseline to end of study. Two summary scores were derived: physical and psychosocial. In accord with the scoring manual, computed scores were transformed giving each scale a possible range from 0 to 100, with the exception of change in health, with a possible range from 1 to 5. For all CHQ-PF50 scales, higher scores indicated more positive functioning or better health status. | From study start to end, up to 3.5 years | 
| Measurement of Trough Total IgG Levels | Measurement of trough total IgG levels from baseline to end of study | From study start to end, up to 3.5 years | 
| Number of Participants With Serious Bacterial Infections (SBIs). | Number of participants with serious bacterial infections | From study start to end, up to 3.5 years |