Study of ProMetic BioTherapeutics Immune Globulin Intravenous (Human) 10%

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

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).

Study Overview

• Status: Completed
• Conditions: Primary Immunodeficiency
• Intervention / Treatment: Biological: Immune Globulin Intravenous; Biological: Prometic's Immune Globulin Intravenous 10%

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.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Irvine, California, United States, 92697
      • University of California, Irvine
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Immunoe International Research
    • Denver, Colorado, United States, 80206
      • National Jewish Hospital
  • Florida
    • North Palm Beach, Florida, United States, 33408
      • Allergy Associates of the Palm Beaches
    • Saint Petersburg, Florida, United States, 33701
      • Johns Hopkins All Children's Hospital
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46815
      • Fort Wayne Medical Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • St. Louis University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43236
      • Optimed Research
  • Texas
    • Dallas, Texas, United States, 75230
      • Dallas Allergy Immunology
  • Washington
    • Bellingham, Washington, United States, 98225
      • Bellingham Asthma, Allergy and Immunology Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Gammargard, Gammaplex, Gamunex, or Octogam Treatment Period; Subjects who enroll in the study while on Gammargard, Gammaplex, Gamunex, or Octogam IGIV Product and need to wait for the scheduled start of Prometic IGIV (10%) treatment will continue on their usual dose and treatment cycle with Gammargard, Gammaplex, Gamunex, or Octogam IVIG Product during this period.	Biological: Immune Globulin Intravenous; Gammargard, Gammaplex,Gamunex, or Octogam IGIV Product
Experimental: Prometic IGIV 10% Treatment Period; Subjects will receive Prometic Immune Globulin Intravenous 10%	Biological: Prometic's Immune Globulin Intravenous 10%; Liquid formulation of Prometic Immune Globulin Intravenous 10% (human) in 50 mL vials containing 100 mg/mL of immunoglobulin G (IgG)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annual Rate of Occurrence of Serious Bacterial Infections (SBI)	SBIs were calculated for each subject as 52n/w, where n is the number of reported SBIs and w is the number of weeks on study. For the combined cohorts only, a 99% one-sided (upper) confidence limit for the incidence rate of SBIs (scaled to represent 12 months exposure if necessary) was derived, and the objective of demonstrating that the true infection rate was below 1 per subject per year was considered established if this upper limit was less than 1. To calculate the confidence limit, a negative binomial regression model will be used. This model includes an overdispersion parameter to account for possible intra-subject correlation as well as the actual time period each subject is on the study as an offset variable.	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough Levels of IgG (Total) Prior to Each Prometic IGIV 10% Infusion	Subject's total IgG levels will be assessed prior to each Prometic IGIV 10% infusion	One year

Collaborators and Investigators

• Sponsor: Prometic Biotherapeutics, Inc.
• Collaborators: Atlantic Research Group
• Investigators: Study Chair: James Moy, MD, Rush University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2016
• Primary Completion (Actual): January 11, 2019
• Study Completion (Actual): January 11, 2019

Study Registration Dates

• First Submitted: October 16, 2014
• First Submitted That Met QC Criteria: October 16, 2014
• First Posted (Estimate): October 20, 2014

Study Record Updates

• Last Update Posted (Actual): November 5, 2021
• Last Update Submitted That Met QC Criteria: November 3, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin; Immunoglobulin G
• Other Study ID Numbers: 2004C009G