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

NCT00419341 | Completed Phase 3 Results

• 2 other identifiers: ZLB04_009CR1458
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 13

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).

Conditions

Primary Immune Deficiency

Keywords

Immune globulin subcutaneous; SCIG; Primary immunodeficiency; PID

Outcome Measures

Primary Outcomes (2)

• 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)

• 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

Secondary Outcomes (12)

• Annualized Rate of Clinically Documented SBIs (ITT Population)

  For the duration of the study, up to 15 months

• Annualized Rate of Clinically Documented SBIs (PPE Population)

  Efficacy period: up to 12 months (week 13 to the completion visit)

• Annualized Rate of Infection Episodes

  Efficacy period: up to 12 months (week 13 to completion visit)

• Number of Infection Episodes (Serious and Non-serious)

  Efficacy period: up to 12 months (week 13 to the completion visit)

• Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections

  Efficacy period: up to 12 months (week 13 to the completion visit)

Other Outcomes (3)

• Minimum Concentration (Cmin) of Total Serum IgG at Steady State

  Week 28 ± 1 week of the treatment period

• Rate of All AEs by Relatedness and Seriousness

  For the duration of the study, up to 15 months

• Rate of Mild, Moderate, or Severe Local Reactions

  For the duration of the study, up to 15 months

Study Arms (1)

IgPro20

EXPERIMENTAL

Human Normal Immunoglobulin for Subcutaneous Administration (IgPro20) is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals. The initial weekly dose was determined based on subjects' previous treatment. Dose adjustments could be performed during the wash-in/wash-out period at the discretion of the investigator.

Biological: Human Normal Immunoglobulin for Subcutaneous Administration

Interventions

Human Normal Immunoglobulin for Subcutaneous Administration BIOLOGICAL

Also known as: Hizentra

IgPro20

Eligibility Criteria

• Age: 2 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (13)

Study Site

Los Angeles, California, 90025, United States

Location

Study Site

Los Angeles, California, 90027, United States

Location

Study Site

Centennial, Colorado, 80112, United States

Location

Study Site

North Palm Beach, Florida, 33408, United States

Location

Study Site

Atlanta, Georgia, 30322, United States

Location

Study Site

Fort Wayne, Indiana, 46815, United States

Location

Study Site

Indianapolis, Indiana, 46202, United States

Location

Study Site

Iowa City, Iowa, 52242, United States

Location

Study Site

St Louis, Missouri, 63104-1095, United States

Location

Study Site

Newark, New Jersey, 07103, United States

Location

Study Site

New York, New York, 10029, United States

Location

Study Site

Philadelphia, Pennsylvania, 19104, United States

Location

Study Site

Dallas, Texas, 75230, United States

Location

Related 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 Sep;30(5):734-45. doi: 10.1007/s10875-010-9423-4. Epub 2010 May 8.

  PMID: 20454851 RESULT

• 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.

  PMID: 21553933 RESULT

Related Links

• Related Info

MeSH Terms

Conditions

Primary Immunodeficiency Diseases

Interventions

gamma-Globulins; Hizentra

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Clinical Trial Disclosure Manager
• Organization: CSL Behring

clinicaltrials@cslbehring.com

Use email contact.

Study Officials

• Richard L. Wasserman, MD, PhD

  Dallas Allergy Immunology and Medical City Children's Hospital,

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2006
• First Posted: January 8, 2007
• Study Start: November 1, 2006
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: January 25, 2013
• Results First Posted: January 25, 2013

Record last verified: 2012-12

Locations

US (13)