Phase 2/3 Study of IGSC, 20% in PIDD

Condition(s) targeted: Primary Immunodeficiency Diseases(PIDD)

Intervention: Immune Globulin Intravenous (Human), 10% Solution (Biological); Immune Globulin Subcutaneous (Human), 20% Solution (Drug)

Phase: Phase 2/Phase 3

Status: Completed

Sponsored by: Baxalta US Inc.

Official(s) and/or principal investigator(s):
Leman Yel, MD, Study Director, Affiliation: Baxter Healthcare Corporation

The purpose of this study is to develop a 20% subcutaneous (SC) immunoglobulin preparation for the treatment of patients with primary immunodeficiency diseases (PIDD).

Official title: A Clinical Study of Immune Globulin Subcutaneous (Human), 20% Solution (IGSC, 20%) for the Evaluation of Efficacy, Safety, Tolerability and Pharmacokinetics in Subjects With Primary Immunodeficiency Diseases (PIDD)

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Rate of acute serious bacterial infections

Secondary outcome:

Annual rate of all infections per participant

Annual rate of sinus infections per participant

Annual rate of fever episodes per participant

Annual rate of days off school/work or days unable to perform normal daily activities due to illness or infection per participant

Annual rate of days on antibiotics per participant

Annual rate of hospitalizations for illness or infection per participant

Annual rate of days of hospitalizations for illness or infection per participant

Annual rate of acute (urgent or unscheduled) physician visits, or visits to the Emergency Room for illness or infection per participant

Bioavailability of IGSC, 20% as measured by the ratio of immunoglobulin G (IgG) AUCSC (Epoch 4) to IgG AUCIV,0-τ (standardized to 1 week) (Epoch 1) adjusted for dose and dosing frequency (participants ≥12 years old)

Trough levels of IgG (total), IgG subclasses, and specific antibodies to clinically relevant pathogens

Other pharmacokinetics parameters for IgG (total) and one specific antibody (anti- Haemophilus influenzae type b)

Expected trough level increase obtained in Epoch 1 compared to Epoch 2 and a nomogram or table derived from this data to be used to determine the "Individually Adapted Dose" in Epoch 4

Number of serious (SAEs) and non-serious adverse events (AEs) (including and excluding infections) deemed related to the investigational product per participant

Number of serious (SAEs) and non-serious adverse events (AEs) (including and excluding infections) deemed related to the investigational product per infusion

Number of serious (SAEs) and non-serious adverse events (AEs) (including and excluding infections) regardless of relationship to the investigational product per participant

Number of serious (SAEs) and non-serious adverse events (AEs) (including and excluding infections) regardless of relationship to the investigational product per infusion

Number of adverse events (AEs) (including and excluding infections) that begin during or within 72 hours of completion of infusion per participant

Number of adverse events (AEs) (including and excluding infections) that begin during or within 72 hours of completion of infusion per infusion

Number of adverse events (AEs) (including and excluding infections) that begin during or within 24 hours of completion of infusion per participant

Number of adverse events (AEs) (including and excluding infections) that begin during or within 24 hours of completion of infusion per infusion

Number of adverse events (AEs) (including and excluding infections) that begin during or within 1 hour of completion of infusion per participant

Number of adverse events (AEs) (including and excluding infections) that begin during or within 1 hour of completion of infusion

Causally related and/or temporally associated AEs per infusion

Proportion of infusions associated with one or more local AEs (including and excluding infections)

Proportion of participants reporting one or more local AEs (including and excluding infections)

Proportion of infusions for which the infusion rate was reduced and/or the infusion was interrupted or stopped due to tolerability concerns or AEs

Proportion of participants for whom the infusion rate was reduced and/or the infusion was interrupted or stopped due to tolerability concerns or AEs

Proportion of infusions tolerated with intravenous or subcutaneous administration

Short term tolerance - Change in blood pressure

Short term tolerance - Change in heart rate (pulse)

Short term tolerance - Change in respiratory rate

Short term tolerance - Change in body temperature

Incidence of laboratory confirmed hemolysis that occurs following investigational product administration

Quality of life- Pediatric Quality of Life Inventory^TM (PEDS-QL^TM) (observer: parent) for the age group 2 to 4 and 5 to 7 years

Quality of life- PEDS-QL^TM (observer: participant) for the age group 8 to 12, and 13 years (use 13 to 18 years form)

Quality of life- Short-Form 36v2 (SF-36v2) for the age group 14 years and older

Life Quality Index

Treatment Satisfaction Questionnaire for Medication (TSQM)

Minimum age: 2 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Main Inclusion Criteria:

- Documented diagnosis of a form of primary humoral immunodeficiency involving

defective antibody formation and requiring gammaglobulin replacement as defined according to the IUIS Scientific Committee, 2011 and by diagnostic criteria according to Conley et al. (1999). The diagnosis must be confirmed by the Medical Director prior to first treatment with the investigational product (IP) in the study.

- Participant is 2 years or older at the time of screening, and has a minimum body

weight of 13 kg.

- Written informed consent has been obtained from either the participant or the

participant's legally authorized representative prior to any study-related procedures and study product administration

- Participant has been receiving a stable monthly equivalent dose of IgG at an average

minimum dose equivalent to 300 mg/kg bodyweight (BW)/4 weeks and a maximum dose equivalent to 1. 0 gram/kg BW/4 weeks, for a minimum of 12 weeks prior to first treatment with the IP in the study.

- Serum trough level of IgG > 500 mg/dL at screening

- Participant is willing and able to comply with the requirements of the protocol

Main Exclusion Criteria:

- Participant has known history of or is positive at screening for one or more of the

following: hepatitis B surface antigen (HBsAg), polymerase chain reaction (PCR) for Hepatitis C virus(HCV), PCR for human immunodeficiency virus (HIV) Type 1/2

- Abnormal laboratory values at screening meeting any one of the following criteria

(abnormal tests may be repeated once to determine if they are persistent):

- Persistent alanine aminotransferase (ALT) and aspartate amino transferase(AST) >

2. 5 times the upper limit of normal for the testing laboratory

- Persistent severe neutropenia (defined as an absolute neutrophil count [ANC]

≤500/mm^3)

- Creatinine clearance (CLcr) value that is < 60% of normal for age and gender either

measured, or calculated according to the Cockcroft-Gault formula

- Malignancy (other than adequately treated basal cell or squamous cell carcinoma of

the skin or carcinoma in situ of the cervix), unless the disease-free period prior to screening exceeds 5 years

- Participant is receiving anti-coagulation therapy (low dose aspirin at ≤325 mg/day is

permitted) or has a history of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) or sickle cell disease with crisis within 12 months prior to screening or a history of thrombophilia

- Abnormal protein loss (protein losing enteropathy, nephrotic syndrome)

- Anemia that would preclude phlebotomy for laboratory studies according to standard

practice at the site

- Acute serious bacterial infection within 3 months prior to screening

- Ongoing history of hypersensitivity or persistent reactions (urticaria, breathing

difficulty, severe hypotension, or anaphylaxis) following intravenous immunoglobulin, subcutaneous immunoglobulin, and/or Immune Serum Globulin (ISG) infusions

- Severe immunoglobulin A (IgA) deficiency (less than 0. 07g/L) with known anti-IgA

antibodies and a history of hypersensitivity

- Participant is on continuous systemic antibacterial antibiotics at doses sufficient

to treat or prevent bacterial infections, and, in the opinion of the investigator, cannot stop these for the duration of the study without putting the patient at risk of increased infections

- Participant has active infection and is receiving antibiotic therapy for the

treatment of infection at the time of screening

- Bleeding disorder or thrombocytopenia with a platelet count less than 20,000/μL, or

who, in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of subcutaneous therapy

- Total protein > 9 g/dL or myeloma or macroglobulinemia (IgM) or paraproteinemia

- Severe dermatitis that would preclude adequate sites for safe product administration

- Women of childbearing potential meeting any one of the following criteria:

- Participant presents with a positive pregnancy test

- Participant is breast feeding

- Participant intends to begin nursing during the course of the study

- Participant does not agree to employ adequate birth-control measures (e. g.

intrauterine device, diaphragm or condom [for male partner] with spermicidal jelly or foam, or birth control pills/patches) throughout the course of the study

- Participation in another clinical study and exposure to an investigational product or

device within 30 days prior to study enrollment (exception: treatment in a previous Baxter immunoglobulin study)

- Participant is scheduled to participate in another (non-Baxter) non-observational

(interventional) clinical study involving an investigational product or device during the course of the study

University of California, Irvine, Irvine, California 92697, United States

IMMUNOe International Research Centers, Centennial, Colorado 80112, United States

Allergy Associates of the Palm Beaches, North Palm Beach, Florida 33408, United States

Emory University, Atlanta, Georgia 30322, United States

Rush University Medical Center, Chicago, Illinois 60612, United States

Family Allergy and Asthma Research Institute, Louisville, Kentucky 40215, United States

Children's Hospital New Orleans- LSUHSC School of Medicine, New Orleans, Louisiana 70118, United States

Midwest Immunology Clinical and Infusion Center, Plymouth, Minnesota 55446, United States

SSM Cardinal Glennon Children's Medical Center, St Louis, Missouri 63104, United States

Montefiore Medical Center Division of Allergy/Immunology, Bronx, New York 10461, United States

Oklahoma Institute of Allergy and Asthma Clinical Research, Oklahoma City, Oklahoma 73131, United States

Vital Prospects Clinical Research Institute, PC, Tulsa, Oklahoma 74136, United States

Centre Hospitalier Universitaire (CHU) Sainte-Justine, Montreal, Quebec H3H 1C5, Canada

Montreal Children's Hospital- McGill University health Center, Montreal, Quebec HEH 1P3, Canada

Dallas Allergy Immunology Research, Dallas, Texas 75230, United States

Allergy Asthma and Immunology Clinic PA, Irving, Texas 75063, United States

Rocky Mountain Asthma/Allergy/Immunology, Layton, Utah 84041, United States

Medical College of Wisconsin, Milwaukee, Wisconsin 53226, United States

Related publications:

Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol. 1999 Dec;93(3):190-7.

Al-Herz W, Bousfiha A, Casanova JL, Chapel H, Conley ME, Cunningham-Rundles C, Etzioni A, Fischer A, Franco JL, Geha RS, Hammarström L, Nonoyama S, Notarangelo LD, Ochs HD, Puck JM, Roifman CM, Seger R, Tang ML. Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front Immunol. 2011 Nov 8;2:54. doi: 10.3389/fimmu.2011.00054. eCollection 2011.

Starting date: January 2013
Last updated: June 26, 2015