Clinical trial NCT00419341: Study of Subcutaneous Immunoglobulin in Patients With PID Requiring IgG Replacement Therapy
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Immune Deficiency
Keywords: Immune globulin subcutaneous
SCIG
Primary immunodeficiency
PID
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2007-01-08
Enrollment: 49
Sex: ALL
Minimum age (years): 2
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) (MITT Population)
timeFrame: Efficacy period: up to 12 months (week 13 to the completion visit)
measure: Area Under the Concentration-time Curve (AUC) of Total Serum Immunoglobulin G (IgG)
timeFrame: Measured during a single dosing interval after at least 12 weeks of stable subcutaneous (SC) dosing with IgPro20 treatment
Secondary outcomes:
measure: Annualized Rate of Clinically Documented SBIs (ITT Population)
timeFrame: For the duration of the study, up to 15 months
measure: Annualized Rate of Clinically Documented SBIs (PPE Population)
timeFrame: Efficacy period: up to 12 months (week 13 to the completion visit)
measure: Annualized Rate of Infection Episodes
timeFrame: Efficacy period: up to 12 months (week 13 to completion visit)
measure: Number of Infection Episodes (Serious and Non-serious)
timeFrame: Efficacy period: up to 12 months (week 13 to the completion visit)
measure: Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections
timeFrame: Efficacy period: up to 12 months (week 13 to the completion visit)
measure: Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections
timeFrame: Efficacy period: up to 12 months (week 13 to the completion visit)
measure: Annualized Rate of Hospitalization Due to Infection
timeFrame: Efficacy period: up to 12 months (week 13 to the completion visit)
measure: Number of Days of Hospitalization Due to Infections
timeFrame: Efficacy period: up to 12 months (week 13 to the completion visit)
measure: Use of Antibiotics for Infection Prophylaxis and Treatment
timeFrame: Efficacy period: up to 12 months (week 13 to the completion visit)
measure: Total Serum IgG Trough Levels
timeFrame: Every 4 weeks, throughout the 12-month efficacy period
measure: Maximum Concentration (Cmax) of Total Serum IgG at Steady State
timeFrame: Week 28 ± 1 week of the treatment period
measure: Tmax at Steady State
timeFrame: Week 28 ± 1 week of the treatment period
Other outcomes:
measure: Minimum Concentration (Cmin) of Total Serum IgG at Steady State
timeFrame: Week 28 ± 1 week of the treatment period
measure: Rate of All AEs by Relatedness and Seriousness
timeFrame: For the duration of the study, up to 15 months
measure: Rate of Mild, Moderate, or Severe Local Reactions
timeFrame: For the duration of the study, up to 15 months
Locations:
city: Los Angeles
country: United States
facility: Study Site
state: California
city: Los Angeles
country: United States
facility: Study Site
state: California
city: Centennial
country: United States
facility: Study Site
state: Colorado
city: North Palm Beach
country: United States
facility: Study Site
state: Florida
city: Atlanta
country: United States
facility: Study Site
state: Georgia
city: Fort Wayne
country: United States
facility: Study Site
state: Indiana
city: Indianapolis
country: United States
facility: Study Site
state: Indiana
city: Iowa City
country: United States
facility: Study Site
state: Iowa
city: St.Louis
country: United States
facility: Study Site
state: Missouri
city: Newark
country: United States
facility: Study Site
state: New Jersey
city: New York
country: United States
facility: Study Site
state: New York
city: Philadelphia
country: United States
facility: Study Site
state: Pennsylvania
city: Dallas
country: United States
facility: Study Site
state: Texas
Study officials:
affiliation: Dallas Allergy Immunology and Medical City Children's Hospital,
name: Richard L. Wasserman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 Sep;30(5):734-45. doi: 10.1007/s10875-010-9423-4. Epub 2010 May 8.
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: 10.2165/11587030-000000000-00000.