Study of Subcutaneous Immunoglobulin in Patients With PID Requiring IgG Replacement Therapy

Primary Immune Deficiency Clinical Trial

Official title:

A Phase III Open-Label, Prospective, Multicenter Study of the Efficacy, Tolerability, Safety, and Pharmacokinetics of Immune Globulin Subcutaneous (Human), IgPro20 in Subjects With Primary Immunodeficiency (PID)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00419341
• Other study ID #: ZLB04_009CR
• Secondary ID: 1458
• Status: Completed
• Phase: Phase 3
• First received: December 22, 2006
• Last updated: December 16, 2012
• Start date: November 2006
• Est. completion date: October 2008

Study information

• Verified date: December 2012
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to assess the efficacy, tolerability, safety and pharmacokinetics of IgPro20 in patients with primary humoral immunodeficiency (PID).

Description:

The entire study consists of a 12-week wash-in/wash-out period followed by a 12-month treatment period. Pharmacokinetic (PK) parameters were assessed in a sub-group of subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: October 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 75 Years

Eligibility

Inclusion Criteria:

• Male or female aged 2 to 75 years

• Subjects with primary humoral immunodeficiency, namely with a diagnosis of: CVID (Common Variable Immunodeficiency) as defined by PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies) or XLA (X-linked Agammaglobulinemia)

• Written informed consent

Exclusion Criteria:

• Newly diagnosed PID

• Evidence of an active serious infection at the time of screening (i.e., but not limited to: bacteremia/septicemia, pneumonia, fungal osteomyelitis)

• Malignancies of lymphoid cells such as lymphocytic leukemia, Non-Hodgkin's lymphoma and immunodeficiency with thymoma

• Known hyperprolinemia

• Hypoalbuminemia, protein-losing enteropathies, and any proteinuria

• Allergic reactions to immunoglobulins or other blood products

• Known antibodies to Immunoglobulin A (IgA)

• The subject is receiving steroids (oral and parenteral, daily = 0.15 mg of prednisone equivalent/kg/day) or other systemic immunosuppressants

• Female who is pregnant, breast feeding or planning a pregnancy during the course of the study

• Participation in a study with an investigational product other than (IVIG) within 1 month prior to enrollment

• A positive result at screening on any of the following viral markers: Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV) and Hepatitis B virus (HBV)

• Aspartate aminotransferase (ASAT) or Alanine aminotransferase (ALAT) concentration > 2.5 times the upper normal limit (UNL)

• Creatinine concentration > 1.5 times the UNL

• Any condition that is likely to interfere with evaluation of the study drug or satisfactory conduct of the trial

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Immunologic Deficiency Syndromes
• Primary Immune Deficiency

Intervention

Biological:
• Human Normal Immunoglobulin for Subcutaneous Administration

Locations

Country	Name	City	State
United States	Study Site	Atlanta	Georgia
United States	Study Site	Centennial	Colorado
United States	Study Site	Dallas	Texas
United States	Study Site	Fort Wayne	Indiana
United States	Study Site	Indianapolis	Indiana
United States	Study Site	Iowa City	Iowa
United States	Study Site	Los Angeles	California
United States	Study Site	Los Angeles	California
United States	Study Site	New York	New York
United States	Study Site	Newark	New Jersey
United States	Study Site	North Palm Beach	Florida
United States	Study Site	Philadelphia	Pennsylvania
United States	Study Site	St.Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Country where clinical trial is conducted

United States, 

References & Publications (2)

Hagan JB, Fasano MB, Spector S, Wasserman RL, Melamed I, Rojavin MA, Zenker O, Orange JS. Efficacy and safety of a new 20% immunoglobulin preparation for subcutaneous administration, IgPro20, in patients with primary immunodeficiency. J Clin Immunol. 2010 — View Citation

Wasserman RL, Melamed I, Nelson RP Jr, Knutsen AP, Fasano MB, Stein MR, Rojavin MA, Church JA. Pharmacokinetics of subcutaneous IgPro20 in patients with primary immunodeficiency. Clin Pharmacokinet. 2011 Jun;50(6):405-14. doi: 10.2165/11587030-000000000-0 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Minimum Concentration (Cmin) of Total Serum IgG at Steady State		Week 28 ± 1 week of the treatment period	No
Other	Rate of All AEs by Relatedness and Seriousness	The rate of AEs was the number of AEs over the number of infusions administered. At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs.	For the duration of the study, up to 15 months	Yes
Other	Rate of Mild, Moderate, or Severe Local Reactions	In addition to the standard MedDRA System Organ Class (SOC) AE assignments, the category of 'local reactions' was defined to provide the possibility for a combined analysis of local reactions and included AEs of injection site reaction, injection site bruising, infusion site scab, injection site cyst, injection site eczema, injection site irritation, injection site nodule, and injection site pain.; Mild AE: Did not interfere with routine activities; Moderate AE: Interfered somewhat with routine activities; Severe AE: Impossible to perform routine activities.	For the duration of the study, up to 15 months	Yes
Primary	Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) (MITT Population)	The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days.; Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an adverse event (AE) was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.	Efficacy period: up to 12 months (week 13 to the completion visit)	No
Primary	Area Under the Concentration-time Curve (AUC) of Total Serum Immunoglobulin G (IgG)	Evaluate non-inferiority of steady-state IgG area under the concentration-time curves standardized to a 7-day period (sAUCs) for subcutaneous immunoglobulin (SCIG) (IgPro20) versus the sAUC under intravenous immunoglobulin (IVIG) (Privigen) treatment. The sAUC under IVIG was taken from the same subjects in a preceding study (either ZLB03_002CR [NCT00168025] or ZLB05_006CR [NCT00322556]).	Measured during a single dosing interval after at least 12 weeks of stable subcutaneous (SC) dosing with IgPro20 treatment	No
Secondary	Annualized Rate of Clinically Documented SBIs (ITT Population)	The annualized rate was based on the total number of SBIs and the total number of subject study days during the study for all subjects in the specified analysis population and adjusted to 365 days.; Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.	For the duration of the study, up to 15 months	No
Secondary	Annualized Rate of Clinically Documented SBIs (PPE Population)	The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days.; Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.	Efficacy period: up to 12 months (week 13 to the completion visit)	No
Secondary	Annualized Rate of Infection Episodes	The annualized rate was based on the total number of infection episodes occurring during the efficacy period (N = 96) divided by the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.	Efficacy period: up to 12 months (week 13 to completion visit)	No
Secondary	Number of Infection Episodes (Serious and Non-serious)	Total number of infections for the specified analysis population	Efficacy period: up to 12 months (week 13 to the completion visit)	No
Secondary	Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections	The annualized rate was based on the total number of days out of work / school / kindergarten / day care or inability to perform normal activities due to infection (N = 71), and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.	Efficacy period: up to 12 months (week 13 to the completion visit)	No
Secondary	Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections	Total number of days out of work / school / kindergarten / day care or unable to perform normal daily activities due to infections, for the specified analysis population	Efficacy period: up to 12 months (week 13 to the completion visit)	No
Secondary	Annualized Rate of Hospitalization Due to Infection	The annualized rate was based on the total number of days of hospitalization due to infection (N = 7) and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.	Efficacy period: up to 12 months (week 13 to the completion visit)	No
Secondary	Number of Days of Hospitalization Due to Infections	Total number of days of hospitalization due to infections for the specified analysis population	Efficacy period: up to 12 months (week 13 to the completion visit)	No
Secondary	Use of Antibiotics for Infection Prophylaxis and Treatment	Annualized rate of days with antibiotics for infection prophylaxis and treatment. The annualized rate was based on the total number of days of antibiotic use for infection prophylaxis and treatment in the efficacy period, and the total number of subject study days for all subjects in the specified analysis population, and adjusted to 365 days.	Efficacy period: up to 12 months (week 13 to the completion visit)	No
Secondary	Total Serum IgG Trough Levels	The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics.	Every 4 weeks, throughout the 12-month efficacy period	No
Secondary	Maximum Concentration (Cmax) of Total Serum IgG at Steady State		Week 28 ± 1 week of the treatment period	No
Secondary	Tmax at Steady State	Timepoint of maximum concentration (Cmax)	Week 28 ± 1 week of the treatment period	No

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