Study to Investigate Efficacy, Safety and Pharmacokinetics of BT595 in Subjects With PID

Study Overview
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Brief Summary
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This Phase III clinical study is to test efficacy, safety and pharmacokinetics of BT595 in treating patients with Primary Immunodeficiency (PID)

Official Title
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An Open-label, Prospective, Multicenter Study Investigating Clinical Efficacy, Safety, and Pharmacokinetic Properties of the Human Normal Immunoglobulin for Intravenous Administration BT595 as Replacement Therapy in Patients With Primary Immunodeficiency Disease (PID)

Conditions
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Primary Immunodeficiency Disease

Intervention / Treatment
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* Biological: IgG Next Generation (BT595)


Participation Criteria
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Eligibility Criteria
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Criteria for inclusion: Written informed consent/assent obtained from subjects/subjects' parent(s) or legally acceptable representative indicating that they understood the purpose of, and procedures required for the study and are willing to participate in it. Male or female, aged 2 through 75 years, inclusive. Diagnosis of PID with impaired antibody production, ie: - 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 agammaglobulinaemia (XLA) as defined by ESID/PAGID diagnostic criteria. Established replacement therapy with any immunoglobulin for intravenous administration (IVIg) reference preparation during the previous 6 months, including documentation of IgG trough levels. Established replacement therapy with a single IVIg reference preparation for ≥3 months prior to treatment start with BT595 at a 3 week (Q3W) or 4 week (Q4W) 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. Criteria for exclusion: Pregnancy or unreliable contraceptive measures or lactation period (females only). Known intolerance to immunoglobulins or comparable substances (eg, vaccination reaction). Known intolerance to proteins of human origin or known allergic reactions to components of the study product. Participation in another clinical study within 30 days before entering the study or during the study and/or previous participation in this study. Employee or direct relative of an employee of the contract research organization, the study site, or Biotest. 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. Other medical condition, laboratory finding, or physical examination finding that precludes participation. Recent febrile illness that precludes or delays participation. Active infection and receiving antibiotic therapy for the treatment of this infection at the time of screening. Note: if the subject was deemed to be a screen failure due to a nonserious active infection requiring antibiotic therapy, the subject may have been rescreened after the initial screening. Therapy with systemic steroids or other immunosuppressant drugs at the time of enrollment (current daily use of corticosteroids, ie, >10 mg prednisone equivalent/day for >30 days. Intermittent corticosteroid use during the study was allowable, if medically necessary). 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. Therapy with live-attenuated virus vaccines within 3 months before start of the study. Selective, absolute immunoglobulin A (IgA) deficiency or known antibodies to IgA. Positive diagnosis of hepatitis B or hepatitis C. Positive human immunodeficiency virus (HIV) test. History of drug or alcohol abuse within the 12 months before treatment start with BT595. Inability or lacking motivation to participate in 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: BT595<br>Subjects received BT595 (100 mg/mL human normal immunoglobulin) at doses between 0.2 and 0.8 g per kg body weight (bw) (2 to 8 mL/kg bw), either at a Q3W or Q4W schedule, The initial doses and dosage interval had to be consistent with the subject's prestudy IVIg treatment. | Biological: IgG Next Generation (BT595)<br> <br> * Other names: Immune Globulin Intravenous (Human), 10% Liquid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Acute Serious Bacterial Infections | The primary efficacy endpoint was the rate of acute serious bacterial infections, ie, the mean number of acute serious bacterial infections [SBIs as defined by EMA and FDA] per subject-year. | approx. 12 month treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IgG Trough Levels (Total IgG) Before Each Infusion | Total IgG levels [g/L] before each infusion, mean (SD) | approx. 12 month treatment period | 
| Rate of Any Infections | The annual rate of infections was calculated as the number of all infections (serious plus nonserious) per subject-year | approx. 12 month treatment period | 
| Rate of Nonserious Infections | The annual rate of nonserious infections was calculated as the number of nonserious infections per subject-year | approx. 12 month treatment period | 
| Time to Resolution of Infections | Time to resolution of infections (days) was calculated as infection stop date - infection start date +1. | approx. 12 month treatment period | 
| Antibiotic Treatment Information | Median (min-max) number of days on antibiotics treatment per subject | approx. 12 month treatment period | 
| Rate of Time Lost From School/Work Due to Infections | Annual rates of the number of days subjects are not able to attend school/work due to infections and their treatment will be calculated per subject-year. | approx. 12 month treatment period | 
| Hospitalization / Hospitalization Due to Infection | Annual rates of the number of days of hospitalization (any hospitalization/ hospitalization due to infection) will be calculated per subject-year. | approx. 12 month treatment period | 
| Fever Episodes | The number of days with episodes of fever will be calculated as the number of fever episodes per subject-year. Fever is defined as a body temperature ≥38°C (≥100.4°F). | approx. 12 month treatment period |