Clinical trial NCT01289847: A Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Primary Immune Deficiency Disorders
Common Variable Immunodeficiency
X-linked Agammaglobulinemia
Hyper-IgM Syndrome
Wiskott-Aldrich Syndrome
Keywords: Primary Immune Deficiency Disorders
Common Variable Immunodeficiency
X-linked agammaglobulinemia
Hyper-IgM syndrome
Wiskott-Aldrich Syndrome
Immunoglobulins
Bacterial Infections
Lead sponsor: Bio Products Laboratory
Sponsor class: OTHER
First posted: 2011-02-04
Enrollment: 25
Sex: ALL
Minimum age (years): 2
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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


Eligibility 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 treatments for 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.

Primary outcomes:
measure: Adverse Events
timeFrame: 12 months
Secondary outcomes:
measure: Therapeutic Efficacy
timeFrame: From week 15 onwards
measure: Therapeutic Efficacy
timeFrame: 12 months
measure: Therapeutic Efficacy
timeFrame: 12 months
measure: Therapeutic Efficacy
timeFrame: 12 months
measure: Therapeutic Efficacy
timeFrame: 12 months
Other outcomes:
Locations:
city: Irvine
country: United States
facility: Department of Medicine, University of California
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Centennial
country: United States
facility: IMMUNOe International Reseach Centers
state: Colorado
city: Atlanta,
country: United States
facility: Family Allergy & Asthma Center, PC
state: Georgia
city: Chicago,
country: United States
facility: Rush University Medical Center
state: Illinois
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Irving
country: United States
facility: Allergy, Asthma & Immunology Clinic, P.A
state: Texas
city: Richmond
country: United States
facility: Children's Hospital of Richmond, VA
state: Virginia
city: Santiago
country: Chile
facility: Hospital de Niňos Roberto del Río
city: Tel-Hashomer
country: Israel
facility: Safra Children's Hospital, Sheba Medical Center
Study officials:
affiliation: Medical Director
name: Tim J. Aldwinckle, MD
role: STUDY_DIRECTOR
References: