Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases.
Information source: Bio Products Laboratory
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Primary Immunodeficiency; Common Variable Hypogammaglobulinemia; X-linked Hypogammaglobulinemia; Hypogammaglobulinemia; Immunodeficiency With Hyper-IgM; Wiskott-Aldrich Syndrome
Intervention: Gammaplex (Intravenous immunoglobulin) (Biological)
Phase: Phase 3
Sponsored by: Bio Products Laboratory
Official(s) and/or principal investigator(s):
Melvin Berger, MD, Principal Investigator, Affiliation: Rainbow Babies & Children's Hospital, Cleveland, Ohio
The main objective of this study is to see if GAMMAPLEX is efficacious with respect to Food
and Drug Administration (FDA) minimal requirements (no more than 1 serious, acute, bacterial
infection per subject per year) in subjects with Primary Immunodeficiency Diseases (PID).
The secondary objectives are to assess the safety and tolerability of GAMMAPLEX and to
determine if GAMMAPLEX has a pharmacokinetic (PK) profile comparable with that of intact
Immunoglobulin G (IgG) in subjects with PID.
Official title: A Phase III, Multicenter, Open-Label Study To Evaluate The Efficacy, Safety, and Pharmacokinetics of Gammaplex® in Primary Immunodeficiency Diseases
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Number of Serious, Acute, Bacterial Infections (SABIs) Per Subject Per Year in Subjects With Primary Immunodeficiency Disease.
The Pharmacokinetic (PK) Half-Life of Immunoglobulin G (IgG)
The Pharmacokinetic (PK) Clearance of Immunoglobulin G (IgG)
The Pharmacokinetic (PK) Volume of Distribution (Vz)of Immunoglobulin G (IgG)
The Pharmacokinetic (PK) Mean Residence Time (MRT) for Inmuunoglobulin G (IgG)
Primary Efficacy Variable The primary variable is the number of serious, acute, bacterial
infections/subject/year, and it will be based on the total of all of the following events as
defined by the FDA: bacterial Pneumonia, bacteremia/sepsis, osteomyelitis/septic arthritis,
visceral abscess, and bacterial meningitis.
Secondary Efficacy Variables Secondary efficacy will be determined by using the following
variables: number of days of work/school missed because of infection per subject year;
number and days of hospitalizations because of infection per subject year; number of visits
to physicians for acute problems and/or number of visits to hospital emergency rooms per
subject year; other infections documented by fever or a positive result on a radiograph
and/or culture; number of infectious episodes per subject per year; number of days on
therapeutic antibiotics. These data will be entered into the subject diary, confirmed by the
physician, and entered on the electronic-CRF (e-CRF).
Safety Variables. The variables used to assess safety will be the following: adverse events
(AEs); vital signs; clinical laboratory tests and Direct Coombs' Test; transmission of
viruses; physical examination.
Test product, dose/mode of administration, batch number(s): The GAMMAPLEX dose is 300-800
mg/kg/infusion (milligram per killgram per infusion) every 21 or 28 days, intravenously. At
least 2 batches will be used in this study and no more than 1 batch in any given infusion.
Duration of treatment:
The total duration of treatment is 12 months.
Minimum age: 3 Years.
Maximum age: N/A.
- 1. The subject is 3 years of age or older, of either sex, belonging to any ethnic
group, and above a minimum weight of 27. 5 kg. This weight is based on the amount of
blood required for testing. If subject is participating in the PK segment, the
minimum weight required is 37 kg.
2. The subject has a primary immunodeficiency disease, which has as a significant
component of hypogammaglobulinemia and/or antibody deficiency (e. g. (exempli gratia /
for example), common variable immunodeficiency, X-linked and autosomal forms of
agammaglobulinemia, hyper-immunoglobulin M (hyper-IgM) syndrome, Wiskott-Aldrich
Syndrome). Isolated deficiency of a single IgG subclass, or of specific antibodies
without hypogammaglobulinemia per se, does not qualify for inclusion.
3. The subject has been receiving licensed or investigational (Phase III or IIIb)
immunoglobulin intravenous (IGIV) replacement therapy at a dose that has not changed
by + 50% of the mean dose for at least 3 months before study entry and is between 300
and 800 mg/kg/infusion. The infusion interval must be between 21 and 28 days
inclusive. The subject must have maintained a trough level at least 300 mg/dL
(milligram per decilitre) above baseline serum IgG levels (defined as before
initiation of any gamma globulin treatment for that subject). The trough level must
be 600 mg/dL.
4. Trough levels of IgG and dose of IGIV, treatment intervals, and the trade name of
the IGIV treatments used for the last 2 consecutive routine (licensed or
investigational product) must be documented for each subject before the first
infusion in this study can be administered.
5. If a subject is a female of child-bearing potential, she must have a negative
result on an Human Chorionic Gonadotrophin (HCG)-based pregnancy test.
6. 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.
7. The subject is willing to comply with all aspects of the protocol, including blood
sampling, for the duration of the study.
8. The subject has signed an informed consent form (if at least 18 years old) or the
subject's parent or legal guardian has signed the informed consent form. If
appropriate, the subject has signed a child assent form (See Section 12. 3).
- Subjects will be excluded if any of the following exclusion criteria are met:
1. The subject has a history of any severe anaphylactic reaction to blood or any
2. The subject is known to be intolerant to any component of GAMMAPLEX, such as
sorbitol (i. e.(id est / that is) , intolerance to fructose).
3. The subject has selective immunoglobulin A (IgA) deficiency, history of reaction
to products containing IgA, or has a history of antibodies to IgA.
4. Subjects who have completed the study and subjects who have withdrawn cannot
participate in the study for a second time.
5. 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.
6. 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 or an ISG product that is in Phase III
or IIIb studies.
7. The subject is pregnant or is nursing.
8. The subject is positive for any of the following at screening:
- Serological test for Human immunodeficiency virus (HIV) 1&2, Hepatitis C
virus (HCV), or Hepatitis B surface antigen (HBsAg)
- Nucleic Acid test (NAT) for HCV
- NAT for HIV
9. 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)
10. The subject has a severe renal impairment (defined as serum creatinine greater
than 2 times the upper limit of normal or Blood urea nitrogen (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
11. The subject is known to abuse alcohol, opiates, psychotropic agents, or other
chemicals or drugs, or has done so within the past 12 months.
12. The subject has a history of deep vein thrombosis (DVT), or thrombotic
complications of IGIV therapy.
13. The subject suffers from any acute or chronic medical condition (e. g., renal
disease or predisposing conditions for renal disease, coronary artery disease,
or protein losing state) that, in the opinion of the investigator, may interfere
with the conduct of the study.
14. The subject has an acquired medical condition, such as chronic lymphocytic
leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (Absolute
neutrophil count (ANC) < 1000 x 109/L).
15. The subject is receiving the following medication:
- Immunosuppressive drugs
- The subject is receiving the following medication: Steroids (long-term
daily, >0. 15 mg /kg/day of prednisone or prednisolone of equivalent dose of
other corticosteroids) The requirement for burst or intermittent courses
would not exclude the subject.
- Immunomodulatory drugs
16. The subject has non-controlled arterial hypertension (systolic blood pressure >
160 mmHg (millimeters of mercury) and/or diastolic blood pressure > 100 mmHg).
17. The subject has anemia (hemoglobin < 10 g/dL) at screening.
Locations and Contacts
Allergy Associates of the Palm Beaches, North Palm Beach, Florida 33408, United States
Family Allergy and Asthma Center PC, Atlanta, Georgia 30342, United States
Rush University Medical Centre, University Consultants in Allergy & Immunology, Chicago, Illinois 60612, United States
Childrens Hospital at Buffalo, Allergy Division, Buffalo, New York 14222, United States
Allergy, Asthma & Immunology Clinic, P.A., Irving, Texas 75063, United States
UCLA Medical Centre, Irving, Texas 75063, United States
University of Washington School of Medicine, Dept. of Pediatrics, Seattle, Washington 989109-5235, United States
Starting date: January 2006
Last updated: January 23, 2013