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

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

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.

Study Overview

• Status: Completed
• Conditions: Common Variable Immunodeficiency; Agammaglobulinemia
• Intervention / Treatment: Drug: Vivaglobin

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Contact CSL Behring for facility details
  • Quebec
    • Montreal, Quebec, Canada, H3H 1P3
      • Contact CSL Behring for facility details
• Germany
  • Leipzig, Germany, 04129
    • Contact CSL Behring for facility details
• Italy
  • Brescia, Italy, 25123
    • Contact CSL Behring for facility details
  • Roma, Italy, 00186
    • Contact CSL Behring for facility details
• Spain
  • Madrid, Spain, 28007
    • Contact CSL Behring for facility details

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vivaglobin; 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; Human normal immunoglobulin G (IgG) for subcutaneous (SC) use.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Principal Investigator: Michael Borte, MD, Klinik für Kinder-und Jugendmedizin am Städtischen Klinikum St. Georg, Leipzig, Germany

Publications and helpful links

General Publications

• Borte M, Quinti I, Soresina A, Fernandez-Cruz E, Ritchie B, Schmidt DS, McCusker C. Efficacy and safety of subcutaneous vivaglobin(R) replacement therapy in previously untreated patients with primary immunodeficiency: a prospective, multicenter study. J Clin Immunol. 2011 Dec;31(6):952-61. doi: 10.1007/s10875-011-9588-5. Epub 2011 Sep 20.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: August 23, 2007
• First Submitted That Met QC Criteria: August 23, 2007
• First Posted (Estimate): August 24, 2007

Study Record Updates

• Last Update Posted (Estimate): June 20, 2013
• Last Update Submitted That Met QC Criteria: June 12, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Quality of life; Primary Immunodeficiency (PID); CVID; XLA; Previously Untreated Patient (PUP); Subcutaneous immunoglobulin (SCIG); IgG trough level; Common variable immunodeficiency (CVID); X-linked agammaglobulinemia (XLA)
• Additional Relevant MeSH Terms: Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Blood Protein Disorders; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Agammaglobulinemia; Common Variable Immunodeficiency
• Other Study ID Numbers: ZLB06_005CR; 1461 (Other Identifier: CSL Behring); 2006-006522-25 (EudraCT Number)