Clinical trial NCT02269163: Study of ProMetic BioTherapeutics Immune Globulin Intravenous (Human) 10%
Official title: A Phase 3, Multicenter, Open-Label Study of the Safety, Tolerability, Efficacy, and PK of ProMetic BioTherapeutics IGIV (Human) 10% in Adults and Children With Primary Immunodeficiency Diseases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Immunodeficiency
Lead sponsor: Prometic Biotherapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Atlantic Research Group
First posted: 2014-10-20
Enrollment: 82
Sex: ALL
Minimum age (years): 2
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Phase 3 multicenter, open-label study of safety, tolerability, efficacy, and pharmacokinetics (PK) of ProMetic's Immune Globulin Intravenous (Human) 10%, the investigational medicinal product \[IMP\]), in Adults and Children with Primary Immunodeficiency Diseases (PIDD).

Detailed description: This is a pivotal Phase 3, open-label, single-arm, multicenter study to assess the tolerability, safety, efficacy, and Pharmacokinetics of the Investigational Medicinal Product in adults and children with Primary Immunodeficiency Diseases (PIDD). A total of approximately 75 subjects aged 2-80 years will be enrolled in the study. Subjects who switch from an investigational immune globulin or subcutaneous immune globulin (IGSC) are required to receive a stable dose of commercial product (CP), which is a licensed commercially available immune globulin intravenous (IGIV) product for at least 3 cycles before they can be given the Investigational Medicinal Product . This study schema will result in the Commercial Product Treatment Period and Investigational Medicinal Product Treatment Period. All subjects will be treated on an outpatient basis with the Investigational Medicinal Product for approximately 1 year, with the dose and schedule based on their previous IGIV treatment regimen (21-day or 28-day dosing interval). A subset of subjects will participate in a Pharmacokinetics sub-study.

The primary objective of the study is to examine the rate of clinically documented serious bacterial infections (SBIs) in subjects treated with the Investigational Medicinal Product to achieve a rate of less than one SBI per year.

Eligibility criteria: Inclusion Criteria:

1. Subject is male or female between the ages of 2 and 80 years at Screening.
2. Female subjects of childbearing potential must agree to employ adequate birth control measures, as determined by their IRB/IEC, for the duration of the study.
3. The subject must have one of the following three diagnoses (isolated PIDD of other types will be excluded):

   * Common variable immunodeficiency
   * X-linked agammaglobulinemia
   * Hyper-IgM syndrome and documented low IgG levels (\<4.5 mg/mL \[450 mg/dL\]).
4. Subjects must have been treated with a stable dose of immune globulin administered intravenously (IGIV) or subcutaneously (IGSC) and has documented trough or steady state IgG levels of ≥ 5 mg/mL.

Exclusion Criteria:

1. Subject has secondary immunodeficiency or has been diagnosed with dysgammaglobulinemia or isolated IgG subclass deficiency; has known hypoalbuminemia (\<3 gm/dL), protein-losing enteropathy, or nephrotic syndrome.
2. Subject has ever had a history of severe anaphylactic or anaphylactoid reaction to immunoglobulins or other blood products.
3. Subject has a known history of immunoglobulin A (IgA) deficiency and known anti-IgA antibodies, thrombotic event, such as deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism, at any time.
4. Subject has received blood products except IGIV, IGSC, or albumin within the previous 12 months or has participated in another study (except for IGIV, IGSC studies) within the previous 4 weeks.
5. Subject has had cancer in the past 5 years, except for basal cell or squamous cell cancers of the skin.
6. Subject has had a documented active infection within 7 days prior to Screening, or subject is on continuous prophylactic antibiotics.
7. Subject is positive for human immunodeficiency virus (HIV)-1 or HIV-2, a positive hepatitis C virus (HCV) or hepatitis B virus (HBV).
8. Subject has levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.5 times the upper limit of normal (ULN).
9. Subject has serum creatinine \>1.5 times the ULN or a severe chronic condition such as renal failure with proteinuria.
10. Subject has anemia with a hemoglobin level ≤8 g/dL.
11. Subject has severe neutropenia with neutrophil count ≤1000 per mmᴧ3 or has lymphopenia with \<500 per/ mmᴧ3.
12. Subject is taking prednisone at a dose ≥0.15 mg/kg/day and receiving other immunosuppressive drugs or chemotherapy.
13. Subject has known atrial fibrillation requiring anticoagulant therapy; congestive heart failure (New York Heart Association Class III/IV); cardiomyopathy; or cardiac arrhythmia associated with thromboembolic events, unstable or advanced ischemic heart disease, or hyperviscosity.
14. Subject has known decreased Protein C and/or Protein S levels.
15. Subject is positive for antibodies to β2GPI and/or β2GPI DI at Screening.
16. Female subject who is pregnant, breast-feeding, or planning a pregnancy during the course of the study.
17. A history of epilepsy or multiple episodes of migraine (defined as at least one episode within 6 months of enrolment) not completely controlled by medication, or any condition that is likely to interfere with evaluation of the IMP or satisfactory conduct of the study in the Investigator's opinion.

Primary outcomes:
measure: Annual Rate of Occurrence of Serious Bacterial Infections (SBI)
timeFrame: One year
Secondary outcomes:
measure: Trough Levels of IgG (Total) Prior to Each Prometic IGIV 10% Infusion
timeFrame: One year
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California, Irvine
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Centennial
country: United States
facility: Immunoe International Research
state: Colorado
city: Denver
country: United States
facility: National Jewish Hospital
state: Colorado
city: North Palm Beach
country: United States
facility: Allergy Associates of the Palm Beaches
state: Florida
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Institute
state: Indiana
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Optimed Research
state: Ohio
city: Dallas
country: United States
facility: Dallas Allergy Immunology
state: Texas
city: Bellingham
country: United States
facility: Bellingham Asthma, Allergy and Immunology Clinic
state: Washington
Study officials:
affiliation: Rush University Medical Center
name: James Moy, MD
role: STUDY_CHAIR
References: