A Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bio Products Laboratory
ClinicalTrials.gov Identifier:
NCT01289847
First received: January 27, 2011
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

The main objective is to determine the efficacy of Gammaplex by measuring the number of serious acute bacterial infections during treatment with Gammaplex over a 12 month period. The secondary objectives are to assess the safety and tolerability of Gammaplex and to compare the data collected from adult subjects with PID from the GMX01 study


Condition Intervention Phase
Primary Immune Deficiency Disorders
Common Variable Immunodeficiency
X-linked Agammaglobulinemia
Hyper-IgM Syndrome
Wiskott-Aldrich Syndrome
Biological: Gammaplex
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase IV, Multicenter, Open-Label Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases (PID) in Children and Adolescents

Resource links provided by NLM:


Further study details as provided by Bio Products Laboratory:

Primary Outcome Measures:
  • Adverse events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Number of subjects with serious, acute, bacterial infections as a measure of efficacy


Secondary Outcome Measures:
  • Therapeutic efficacy [ Time Frame: From week 15 onwards ] [ Designated as safety issue: No ]
    Number and proportion of subjects who maintain trough IgG levels at least as high as the average of the 2 previous trough levels before the first Gammaplex infusion

  • Therapeutic efficacy [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Number of infections, days off school, days in hospital, visits to physicians and/or emergency room, days on antibiotics

  • Adverse events [ Time Frame: During infusion or within 72 hours after end of infusion. Also the data from this study will be compared to a previous Gammaplex PID study in adults (GMX01). ] [ Designated as safety issue: Yes ]
  • Adverse events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Nature, severity and frequency of Adverse Events

  • Vital signs [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Clinically significant changes in vital signs will be classified as adverse events

  • Laboratory testing [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Clinically significant changes in laboratory tests, hematology, clinical chemistry, Direct Coombs' Test and urine analysis

  • Assessment of viral safety [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Clinically significant changes from baseline will be classified as adverse events

  • Physical examination [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Clinically significant changes from baseline will be recorded as adverse events

  • Pharmacokinetics [ Time Frame: Screening, Infusions 7-10, then every other infusion to 1st follow up visit ] [ Designated as safety issue: No ]
    Trough levels of antibodies against 3 specific antigens

  • Pharmacokinetics [ Time Frame: At infusion 7 or 9 (of 13 of 17 infusions) over 28 days ] [ Designated as safety issue: No ]
    Pharmacokinetics of Gammaplex for total IgG

  • Interval medical history [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Clinically significant changes in medical history will be classified as adverse events

  • Pharmacokinetics [ Time Frame: Screening, Infusion 1, Infusion 2 (IgG only), Infusion 4, Infusion 6 to 10, then every other infusion until Follow up 1 ] [ Designated as safety issue: No ]
    Trough levels of IgG, IgG subclasses (1-4)


Enrollment: 25
Study Start Date: March 2011
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gammaplex Biological: Gammaplex
GAMMAPLEX 5g/100 mL, dose is 300-800 mg/kg/infusion every 21 or 28 days, intravenously. The total duration of treatment with GAMMAPLEX will be 12 months with a 3 month follow-up.

  Eligibility

Ages Eligible for Study:   2 Years to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The subject is between the ages of or is equal to 2 and 16 years of age, of either sex, belonging to any ethnic group, and above a minimum weight of 10 kg. This weight is based on the amount of blood required for testing.
  • The subject has a primary immunodeficiency disease, which has as a significant component of hypogammaglobulinemia and/or antibody deficiency (e.g. common variable immunodeficiency, X-linked and autosomal forms of agammaglobulinemia, hyper-IgM syndrome, Wiskott-Aldrich Syndrome). NB Isolated deficiency of a single IgG subclass, or of specific antibodies without hypogammaglobulinemia per se, does not qualify for inclusion.
  • Subjects already receiving IGIV replacement therapy require the following before their first infusion of Gammaplex:
  • Documented IGIV dose(s) and treatment intervals for the last 2 consecutive routine IGIV treatments (one of which can be the screening visit result). The previous doses should also meet the following conditions before study entry: Have not changed by ± 50% of the mean dose for at least 3 months; be between 300 and 800 mg/kg/infusion; be given every 21-28 days, inclusive; be a licensed or investigational product (Phase III or IIIb).
  • Documented previous IgG trough levels for the last 2 consecutive routine IGIV treatmentsfor the last 2 consecutive routine IGIV treatments: Maintained at least 300 mg/dL above baseline serum IgG levels (defined as before initiation of any gamma globulin treatment for that subject); must be more than/equal to 600 mg/dL.
  • If a subject is a female of child-bearing potential, she must have a negative result on an HCG-based pregnancy test.
  • If a subject is a female who is or becomes sexually active, she must practice contraception by using a method of proven reliability for the duration of the study.
  • The subject is willing to comply with all aspects of the protocol, including blood sampling, for the duration of the study.
  • The subject, if old enough (generally 6 years to 16), has signed a Child Assent Form and the subject's parent or legal guardian has signed the Informed Consent Form, both approved by the IEC/IRB.

Exclusion Criteria:

  • Has not been treated with IGIV (treatment naive subject)
  • The subject has a history of any severe anaphylactic reaction to blood or any blood-derived product.
  • The subject is known to be intolerant to any component of Gammaplex, such as sorbitol (i.e. intolerance to fructose).
  • The subject has selective IgA deficiency, history of reaction to products containing IgA, or has a history of antibodies to IgA.
  • Subjects who have completed the study and subjects who have withdrawn cannot participate in the study for a second time.
  • The subject is currently receiving, or has received, any investigational agent, other than an immune serum globulin (ISG) preparation that is being evaluated in a Phase III or IIIb study, within the prior 3 months.
  • The subject has been exposed to blood or any blood product or derivative within the last 6 months, other than a commercially available IGIV or other forms of commercially available and licensed ISG. If an unlicensed ISG product that is in Phase III or IIIb has been given, the subject cannot be infused with Gammaplex until 20 days after the last dose was given.
  • The subject is pregnant or is nursing.
  • The subject, at screening, has levels greater than 2.5 times the upper limit of normal as defined at the central laboratory of any of the following: (Alanine transaminase (ALT); Aspartate transaminase (AST) Lactate dehydrogenase (LDH)).
  • The subject has a severe renal impairment (defined as serum creatinine greater than 2 times the upper limit of normal or BUN 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.
  • The subject is known to abuse alcohol, opiates, psychotropic agents, or other chemicals or drugs, or has done so within the past 12 months.
  • The subject has a history of DVT, or thrombotic complications of IGIV therapy.
  • The subject suffers from any acute or chronic medical condition (e.g. renal disease or predisposing conditions for renal disease, or protein losing state) that, in the opinion of the investigator, may interfere with the conduct of the study.
  • The subject has an acquired medical condition, such as, chronic or recurrent neutropenia (ANC < 1000 x 109/L) or AIDS known to cause secondary immune deficiency, or is post or recovering from hematopoietic stem cell transplantation.
  • The subject is receiving the following medication: Systemic long-term corticosteroids (i.e. not intermittent or burst, daily, >1 mg of prednisone equivalent/kg/day).
  • The subject is receiving Immunosuppressive or Immunomodulatory drugs.
  • The subject has non-controlled arterial hypertension.
  • The subject has anemia (hemoglobin <10 g/dL) at screening.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01289847

Locations
United States, California
Department of Medicine, University of California
Irvine, California, United States, 92697.
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
United States, Colorado
IMMUNOe International Reseach Centers
Centennial, Colorado, United States, 80112
United States, Georgia
Family Allergy & Asthma Center, PC
Atlanta,, Georgia, United States, 30342
United States, Illinois
Rush University Medical Center
Chicago,, Illinois, United States, 60612
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
Allergy, Asthma & Immunology Clinic, P.A
Irving, Texas, United States, 75063
United States, Virginia
Children's Hospital of Richmond, VA
Richmond, Virginia, United States, 23219
Chile
Hospital de Niňos Roberto del Río
Santiago, Chile, 8380418
Israel
Safra Children's Hospital, Sheba Medical Center
Tel-Hashomer, Israel, 52621
Sponsors and Collaborators
Bio Products Laboratory
Investigators
Study Director: Tim J. Aldwinckle, MD Medical Director
  More Information

No publications provided

Responsible Party: Bio Products Laboratory
ClinicalTrials.gov Identifier: NCT01289847     History of Changes
Other Study ID Numbers: GMX04, IND 12569
Study First Received: January 27, 2011
Last Updated: May 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Bio Products Laboratory:
Primary Immune Deficiency Disorders
Common Variable Immunodeficiency
X-linked agammaglobulinemia
Hyper-IgM syndrome
Wiskott-Aldrich Syndrome
Immunoglobulins
Bacterial Infections

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Common Variable Immunodeficiency
Hyper-IgM Immunodeficiency Syndrome
Hyper-IgM Immunodeficiency Syndrome, Type 1
Syndrome
Agammaglobulinemia
Wiskott-Aldrich Syndrome
Genetic Diseases, X-Linked
Immune System Diseases
Disease
Pathologic Processes
Blood Protein Disorders
Hematologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hemorrhagic Disorders
Lymphopenia
Leukopenia
Leukocyte Disorders
Genetic Diseases, Inborn
Dysgammaglobulinemia
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014