Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases

NCT01963143 | Completed Phase 3 Results DMC

• 1 other identifier: GMX07
• Study Type: interventional
• Target: 48
• Locations: 3 countries
• Sites: 17

Brief Summary

The primary objective is to demonstrate the bioequivalence of Gammaplex® 10 intravenous immunoglobulin (IGIV) and Gammaplex® 5% IGIV with respect to area under the curve within a 28-day dosing interval (AUC0-28) in a cohort of adult subjects. The secondary objectives are to demonstrate the bioequivalence of Gammaplex® 10 IGIV and Gammaplex® 5% IGIV with respect to area under the curve within a 21-day dosing interval (AUC0-21) in adult subjects; to assess the pharmacokinetics of Gammaplex 10 IGIV and Gammaplex 5% IGIV including Immunoglobulin G (IgG) trough levels and to investigate the safety and tolerability of Gammaplex 10 IGIV and Gammaplex 5% IGIV in adults subjects; to assess the pharmacokinetics of Gammaplex 10 IGIV including IgG trough levels and to investigate the safety and tolerability of Gammaplex 10 IGIV in pediatric subjects.

Conditions

Primary Immune Deficiency Disorders; Common Variable Immunodeficiency; X-linked Agammaglobulinaemia; Hyper-IgM Syndrome

Outcome Measures

Primary Outcomes (1)

• Primary Bioequivalence Analysis - Area Under the Curve Within a 28-day Dosing Interval (AUC0-28) in Adult Subjects

  After a minimum 5 infusions on each product, at pre-infusion, 10 minutes before end of infusion, 1, 3, 6, 24, 48 hours, 4, 7, 14, 21 and 28 days post-infusion

Secondary Outcomes (2)

• Secondary Bioequivalence Analysis - Area Under the Curve Within a 21-Day Dosing Interval (AUC0-21) in Adult Subjects

  After a minimum 5 infusions on each product, at pre-infusion, 10 minutes before end of infusion, 1, 3, 6, 24, 48 hours, 4, 7, 14 and 21 days post-infusion

• Secondary Bioequivalence Analysis - IgG Trough Levels

  After a minimum 5 infusions on each product, at pre-infusion.

Study Arms (3)

Treatment Sequence 1 - Adults

EXPERIMENTAL

Gammaplex 5% - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days, followed by Gammaplex 10 - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days

Biological: Gammaplex (5%); Biological: Gammaplex 10

Treatment Sequence 2 - Adults

EXPERIMENTAL

Gammaplex 10 - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days, followed by Gammaplex 5% - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days

Biological: Gammaplex (5%); Biological: Gammaplex 10

Pediatrics

EXPERIMENTAL

Gammaplex 10 - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days

Biological: Gammaplex 10

Interventions

Gammaplex (5%) BIOLOGICAL

Treatment Sequence 1 - Adults; Treatment Sequence 2 - Adults

Gammaplex 10 BIOLOGICAL

Pediatrics; Treatment Sequence 1 - Adults; Treatment Sequence 2 - Adults

Eligibility Criteria

• Age: 2 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Adult cohort: The subject is aged 16 to 55 years inclusive, is of either sex, and belongs to any ethnic group.
• Pediatric cohort: The subject is aged 2 to 15 years inclusive, is of either sex, weighs at least 10 kg, and belongs to any ethnic group.
• The subject is currently receiving a licensed IGIV (or investigational stage III, IIIb IGIV) at a dose that has not changed by ± 50% of the mean dose for at least three months before study entry and is between 300 and 800 mg/kg/infusion. The infusion interval must be either every 21 or every 28 days.
• The subject must have a trough level ≥ 6 g/L (600 mg/dL). At least one documented trough level must be available from the three months before Screening.
• The subject must have documentation from the last three consecutive routine IGIV infusions for the following, before the first infusion in this study: dose of IGIV, treatment intervals, and trade name (or identity) of the IGIV treatment.
• Female subjects of childbearing potential must have a negative result on an HCG (human chorionic gonadotropin) based pregnancy test at Screening.
• Females who are or become sexually active must practice contraception using a method of proven reliability for the study duration.
• The subject is willing to comply with all aspects of the protocol for the duration of the study.
• The subject has signed an informed consent form and assent form (if applicable).

You may not qualify if:

• The subject has a history of any severe anaphylactic reaction to blood or any blood derived product.
• The subject has selective IgA deficiency, history of reaction to products containing IgA (Immunoglobulin A), or has a history of antibodies to IgA.
• The subject has cellular or innate impaired immunity (i.e. only subjects with humoral impaired immunity may be included).
• The subject has evidence of an active infection at the time of enrolment.
• The subject has previously completed or withdrawn from this study.
• The subject is currently receiving, or has received, any investigational agent other than an IGIV within the prior three months.
• The subject is pregnant or is nursing.
• The subject has positive results for any of the following at Screening:
• Serological test for HIV 1 and 2, HCV, or HBsAg
• NAT (Nucleic acid amplification technique)for HCV
• NAT for HIV
• The subject has levels \> 2.5 times the upper limit of normal, as defined at the central laboratory, of any of the following at Screening:
• Alanine amino transaminase
• Aspartate amino transaminase
• The subject has severe renal impairment (defined as serum creatinine greater than two times the upper limit of normal or blood urea nitrogen greater than 2.5 times the upper limit of normal for the range of the laboratory doing the analysis); the subject is on dialysis; the subject has a history of acute renal failure.

Sponsors & Collaborators

• Bio Products Laboratory: lead

Study Sites (17)

Arizona Allergy Associates

Chandler, Arizona, 85224, United States

Location

Miller Children's Hospital

Long Beach, California, 90806, United States

Location

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

IMMUNOe International Research Centers

Centennial, Colorado, 80112, United States

Location

Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States

Location

Allergy Associates of the Palm Beaches, PA

North Palm Beach, Florida, 33408, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Institute for Asthma and Allergy

Chevy Chase, Maryland, 20815, United States

Location

Asthma and Allergy Center

Toledo, Ohio, 43617, United States

Location

Dallas Allergy Immunology Research

Dallas, Texas, 75230, United States

Location

University of Utah Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

O&O Alpan, LLC

Fairfax, Virginia, 22030, United States

Location

Bellingham Asthma Allergy and Immunology Clinic

Bellingham, Washington, 98225, United States

Location

Egyesitett Szent Istvan es Szent Laszlo Korhaz

Budapest, Hungary

Location

University Hospital of Wales

Cardiff, Wales, CF14 4XW, United Kingdom

Location

The Royal Free Hospital and Medical School

London, NW3 2QG, United Kingdom

Location

Related Publications (2)

• Rajendram V, Paddick M, More J. Measles neutralising antibody levels in patients receiving intravenous immunoglobulin treatment - a sub-analysis of a randomized, cross-over bioequivalence trial. PLoS One. 2025 Feb 7;20(2):e0316926. doi: 10.1371/journal.pone.0316926. eCollection 2025.

  PMID: 39919133 DERIVED

• Geng B, Clark K, Evangelista M, Wolford E. Low rates of headache and migraine associated with intravenous immunoglobulin infusion using a 15-minute rate escalation protocol in 123 patients with primary immunodeficiency. Front Immunol. 2023 Feb 2;13:1075527. doi: 10.3389/fimmu.2022.1075527. eCollection 2022.

  PMID: 36818468 DERIVED

MeSH Terms

Conditions

Primary Immunodeficiency Diseases; Common Variable Immunodeficiency; Bruton type agammaglobulinemia; Hyper-IgM Immunodeficiency Syndrome

Interventions

gamma-Globulins

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases; Dysgammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Head of Medical Information
• Organization: Bio Products Laboratory

medinfo@bpl.co.uk

+44 (0)20 8957 2200

Study Officials

• Eric Wolford

  Bio Products Laboratory

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2013
• First Posted: October 16, 2013
• Study Start: February 1, 2014
• Primary Completion: January 1, 2016
• Study Completion: May 1, 2016
• Last Updated: March 29, 2017
• Results First Posted: March 29, 2017

Record last verified: 2017-02

Locations

US (14); GB (2); HU (1)