Study of Octanorm Subcutaneous IG in Patients With PID

Study Overview
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Brief Summary
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This is an open-label phase III study with a 12-week wash-in/wash-out period followed by a 12-month efficacy period. The main goals of the study are to assess the efficacy of octanorm in preventing serious bacterial infections (SBI) compared with historical control data and to evaluate the pharmacokinetic (PK) characteristics of octanorm.

Official Title
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Clinical Phase III Study to Evaluate the Pharmacokinetics, Efficacy, Tolerability and Safety of Subcutaneous Human Immunoglobulin (Octanorm 16.5%) In Patients With Primary Immunodeficiency Diseases

Conditions
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Primary Immune Deficiency Disorder

Intervention / Treatment
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* Biological: octanorm 16.5%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of at least 2 years up to and including 75 years. Confirmed diagnosis of PI as defined by the ESID and PAGID and requiring immunoglobulin replacement therapy due to hypogammaglobulinaemia or agammaglobulinaemia. The exact type of PI should be recorded. Patients with at least 6 infusions on regular treatment with any IVIG, there of a minimum of the last 2 months on the same product prior to entering the study. Constant IVIG dose between 200 and 800 mg/kg body weight (±20% of the mean dose for the last 6 infusions). Availability of the IgG trough levels of 2 previous IVIG infusions before enrollment, and maintenance of greater than or equal to 5.0 g/L in the trough levels of these 2 previous infusions. 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. 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 regulatory requirements. Willingness to comply with all aspects of the protocol, including blood sampling, for the duration of the study. Exclusion Criteria: Acute infection requiring intravenous antibiotic treatment within 2 weeks prior to and during the screening period. Known history of adverse reactions to IgA in other products. Patients with body mass index ≥40 kg/m2. Exposure to blood or any blood product or plasma derivatives, other than IVIG treatment for PID, within the past 3 months prior to the first infusion of octanorm. Ongoing history of hypersensitivity or persistent reactions to blood or plasma derived products, or any component of the investigational product (such as Polysorbate 80). Requirement of any routine premedication for IgG administration. History of malignancies of lymphoid cells and immunodeficiency with lymphoma. Severe liver function impairment (ALAT 3 times above upper limit of normal). Known protein-losing enteropathies or proteinuria. Presence of renal function impairment (creatinine greater than 120 uM/L), or creatinine greater than 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). Treatment with oral or parenteral steroids for greater than or equal to 30 days or when given intermittently or as bolus at daily doses greater than or equal to 0.15 mg/kg. Treatment with immunosuppressive or immunomodulatory drugs. Live viral vaccination (such as measles, rubella, mumps and varicella) within the last 2 months prior to first infusion of octanorm. Treatment with any investigational medicinal product within 3 months prior to first infusion of octanorm. Presence of any condition, that is likely to interfere with the evaluation of study medication or satisfactory conduct of the trial. Known or suspected to abuse alcohol, drugs, psychotropic agents or other chemicals within the past 12 months prior to first infusion of octanorm. Known or suspected HIV, HCV, or HBV infection. Pregnant or nursing women. Planned pregnancy during the course of the study.

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. | Biological: octanorm 16.5%<br>* octanorm 16.5%, human normal immunoglobulin for subcutaneous (SC) administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of SBI Per Person-year | The primary efficacy outcome is the rate of SBI (Serious bacterial infections - defined as bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess) per person-year on treatment. | Every 4 weeks until the final evaluation at week 65. | 
| AUC(t) at Steady-State Conditions | The primary endpoint with respect to the PK investigations is the area under the curve AUC(t) (i.e., AUC from time 0 (start of the infusion) to the end of the nominal dosing period, standardised to 1 week) at PKSC2 at steady-state conditions. | Measured at Week 28 before the start of the SC infusion, 10 minutes before the end of the infusion, and at 2 h, 1, 2, 3, 4 and 7 days after the end of the infusion. Calculated and averaged. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Annual Rate of All Infections of Any Kind or Seriousness. | The annual rate of all infections of any kind or seriousness. | Up to 65 weeks | 
| Non-serious Infections | Non-serious infections (total and by category). | Up to 65 weeks | 
| Cmax of Total IgG and IgG Subclasses | Cmax (Maximum Plasma Concentration) of total IgG and IgG Subclasses, where the mean value was calculated and reported | Measured at week 28 | 
| Tmax of Total IgG and IgG Subclasses | Tmax (Time to Maximum Plasma Concentration) of total IgG and IgG Subclasses | Measured at Week 28 for all patients, median value was calculated | 
| AUC of Total IgG and IgG Subclasses | AUC (Area Under the Concentration-Time Curve) of total IgG and IgG Subclasses calculated for all patients and mean value was calculated and reported | Measured at Week 28 | 
| Trough Levels of Serum IgG | Trough levels of serum IgG, IgG1, IgG2, IgG3, IgG4 at PK 7 days after 28th infusion of octanorm measured for all patients and median value was calculated and reported | Measured once at Week 28, seven days after 28th infusion of octanorm | 
| IVIG to Octanorm DCF (Based on the Area Under the Concentration-time Curve [AUCτ]) | IVIG to Octanorm Dose Conversion Factor (based on the area under the concentration-time curve [AUCτ]) -- determined by least-squares regression Model which was without restriction of the intercept. | AUC Measured at Week 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PID