Efficacy and Safety of Vivaglobin® in Previously Untreated Patients With Primary Immunodeficiency

Study Overview
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Brief Summary
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The objective of this study is to assess the efficacy and safety of Vivaglobin in previously untreated patients (PUPs) with primary immunodeficiency (PID) over a 25-week observation period. The purpose is to investigate whether PUPs will respond to subcutaneous immunoglobulin (SCIG) treatment with adequate trough levels without first receiving immunoglobulins by the intravenous route by demonstrating that 100 mg immunoglobulin G/kg body weight (IgG/kg bw) administered on 5 consecutive days (i.e. resulting in a total dose of 500 mg IgG/kg bw) results in an IgG increase to ≥ 5 g/L on Day 12 after initiation of SCIG therapy.

Official Title
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A Multicenter Study on the Efficacy and Safety of Vivaglobin® in Previously Untreated Patients (PUPs) With Primary Immunodeficiency (PID)

Conditions
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Common Variable Immunodeficiency, Agammaglobulinemia

Intervention / Treatment
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* Drug: Vivaglobin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Written informed consent, age-adapted Male or female aged 1 to 70 years Diagnosis of primary humoral immunodeficiency No prior immunoglobulin substitution therapy IgG level of <5 g/L at screening Women of childbearing potential must use medically approved contraception and must have a negative urine pregnancy test at screening Key Exclusion Criteria: Evidence of serious infection between screening and first treatment Bleeding disorders that require medical treatments Any medical disorder causing secondary immune disorders, autoimmune neutropenia, or a clinically significant defect in cell mediated immunity Any condition likely to interfere with evaluation of the study drug or satisfactory conduct of the trial

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 70 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: Vivaglobin<br>Vivaglobin: 16% (160 mg/mL) liquid formulation of human IgG for SC use. Loading dose: 100 mg/kg for 5 consecutive days; maintenance dose: 100 mg/kg 1 to 2 times a week for 24 weeks. | Drug: Vivaglobin<br>* Human normal immunoglobulin G (IgG) for subcutaneous (SC) use.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Achieving Immunoglobulin G (IgG) Levels ≥ 5 g/L on Day 12 |  | On Day 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Achieving IgG Levels ≥ 5 g/L on Day 19 |  | On Day 19 | 
| Proportion of Patients Achieving IgG Levels ≥ 5 g/L on Day 26 |  | On Day 26 | 
| IgG Increase (Change From Baseline) on Day 12 |  | Baseline to Day 12 | 
| Overall Rate of Infections | Annualized rate of any infection. The annualized rate was based on the total number of infections and the total number of patient study days for all patients in the specified analysis population and adjusted to 365 days. Infections were classified as all AEs with the system organ class infections and infestations. | For the duration of the study, up to approximately 25 weeks | 
| Total Serum IgG Trough Levels on Day 12 |  | On Day 12 | 
| Total Serum IgG Trough Levels at Week 25 |  | At Week 25 | 
| Serum Concentrations of Specific IgGs Against Cytomegalovirus, Tetanus, and Measles on Day 12 |  | On Day 12 | 
| Serum Concentrations of Specific IgGs Against Cytomegalovirus, Tetanus, and Measles at Week 25 |  | At Week 25 | 
| Serum Concentrations of Specific IgGs Against H. Influenzae Type B and S. Pneumoniae On Day 12 |  | On Day 12 | 
| Serum Concentrations of Specific IgGs Against H. Influenzae Type B and S. Pneumoniae at Week 25 |  | At Week 25 | 
| Use of Antibiotics for Infection Prophylaxis and Treatment | Number of patients. Medications were classified as antibiotics according to the anatomic therapeutic chemical code. | For the duration of the study, up to approximately 25 weeks | 
| Quality of Life as Measured by the Adapted Short Form-36 Health Survey (SF-36; Age ≥ 14 Years) | The SF-36 is a 36-item questionnaire that measures generic health concepts that are relevant across age, disease, and treatment groups. The questions are grouped into eight domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Scores range from 0 to 100, with higher scores indicating a better health state. | At study completion, approximately Week 25 | 
| Quality of Life as Measured by the Child Health Questionnaire Parent Form-50 (CHQ-PF50; Age ≤ 13 Years) | The CHQ-PF50 is a 50-item questionnaire that measures generic health concepts and is suitable for patients younger than 14 years of age. The questions are grouped into 15 domains: global health, physical functioning, role/social limitations - emotional/behavioral, role/social limitations - physical, bodily pain, behavior, global behavior, mental health, self esteem, general health perceptions, change in health, parental impact - emotional, parental impact - time, family activities, and family cohesion. Scores range from 0 to 100, with higher scores indicating a better health state. | At study completion, approximately Week 25 | 
| Number of Patients With Adverse Events (AEs) by Severity and Relatedness | Mild AE: Did not interfere with activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities. Not related: Explained by factors not involving the drug, no temporal relationship; Possibly related: Occurred within a reasonable time of administration, could also be explained by concurrent disease or other drugs; Probably related: Compelling temporal relationship, could not be explained concurrent disease/other drugs; Related AE: Compelling temporal relationship, known/suspected response to the drug confirmed by improvement on stopping. | For the duration of the study, up to approximately 25 weeks | 
| Rate of AEs by Severity and Relatedness | The rate was the number of AEs over the number of infusions administered. Mild AE: Did not interfere with activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities. Not related: Explained by factors not involving the drug, no temporal relationship; Possibly related: Occurred within a reasonable time of administration, could also be explained by concurrent disease or other drugs; Probably related: Compelling temporal relationship, could not be explained concurrent disease/other drugs; Related AE: Compelling temporal relationship, known/suspected response to the drug confirmed by improvement on stopping. | For the duration of the study, up to approximately 25 weeks | 
| Number of Patients With Local Reactions by Severity and Relatedness | Local reactions included: infusion site erythema, infusion site pain, infusion site pruritus, infusion site rash, infusion site reaction, infusion site swelling, injection site bruising, injection site erythema, injection site irritation, injection site pruritus, injection site swelling, edema peripheral, tenderness, erythema, pruritus, and skin swelling. Mild AE: Did not interfere with activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities. Not related: Explained by factors not involving the drug, no temporal relationship; Possibly related: Occurred within a reasonable time of administration, could also be explained by concurrent disease or other drugs; Probably related: Compelling temporal relationship, could not be explained concurrent disease/other drugs; Related AE: Compelling temporal relationship, known/suspected response to the drug confirmed by improvement on stopping. | For the duration of the study, up to approximately 25 weeks | 
| Rate of Local Reactions by Severity and Relatedness | The rate was the number of local reactions over the number of infusions administered. Local reactions included: infusion site: erythema, pain, pruritus, rash, reaction, swelling; injection site: bruising, erythema, irritation, pruritus, swelling; edema peripheral; tenderness; erythema; pruritus; and skin swelling. Mild AE: Did not interfere with activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities. Not related: Explained by factors not involving the drug, no temporal relationship; Possibly related: Occurred within a reasonable time of administration, could also be explained by concurrent disease or other drugs; Probably related: Compelling temporal relationship, could not be explained concurrent disease/other drugs; Related AE: Compelling temporal relationship, known/suspected response to the drug confirmed by improvement on stopping. | For the duration of the study, up to approximately 25 weeks | 
| Number of Patients With Clinically Relevant Changes in Routine Laboratory Parameters | Laboratory parameters included hematology, serum chemistry, and urinalysis parameters, and were assessed at screening, Week 12 (hematology and serum chemistry) and at the completion visit (approximately Week 25). | At Weeks 12 and 25 | 
| Number of Patients With Clinically Relevant Changes in Vital Signs | Vital signs included heart rate, systolic blood pressure, diastolic blood pressure, and body temperature. | At the screening visit, before and after infusions (Days 1 to 5), and at the completion visit (Week 25) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgG trough level, Previously Untreated Patient (PUP), Primary Immunodeficiency (PID), CVID, XLA, Subcutaneous immunoglobulin (SCIG), Quality of life, Common variable immunodeficiency (CVID), X-linked agammaglobulinemia (XLA)