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

Baxalta

Status and phase: Completed; Phase 3; Phase 2

Conditions: Primary Immunodeficiency Diseases (PID)

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT01218438

170904

Details and patient eligibility

About

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

Enrollment: 86 patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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86 participants in 1 patient group

Study Epochs 1-4

Experimental group

Description:

Epoch 1 (13 weeks): Pharmacokinetic (PK) assessment at 2nd to last infusion (in all participants ≥12 years of age). Participants will be treated intravenously once every 3 or 4 weeks at same monthly equivalent dose as prior to the study. Epoch 2 (12-16 weeks): PK assessment (in first 15 participants ≥12 years of age) at 9th infusion to determine adjusted dose for Epoch 3 and individually adapted dose for Epoch 4. Participants will be treated subcutaneously every 7 days at a dose of IGSC, 20% that is 145% of the weekly equivalent of the IV dose in Epoch 1. Epoch 3 (12 weeks): Participants will be treated subcutaneously every 7 days using the adjusted dose determined in Epoch 2. The individually adapted dose for use in Epoch 4 will also be determined. Epoch 4 (40 weeks): Participants will be treated subcutaneously once every week at the individually adapted dose determined in Epoch 3. PK assessment at 17th infusion.

Treatment:

Drug: Immune Globulin Subcutaneous (Human), 20% Solution

Biological: Immune Globulin Intravenous (Human), 10% Solution