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

NCT ID: NCT01218438

Last Updated: 2021-07-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-28
• Study Completion Date: 2015-03-13

Brief Summary

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

Conditions

Primary Immunodeficiency Diseases (PID)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Study Epochs 1-4

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.

Group Type: EXPERIMENTAL

Immune Globulin Intravenous (Human), 10% Solution

Intervention Type: BIOLOGICAL

Intravenous infusion with IGIV, 10%

Immune Globulin Subcutaneous (Human), 20% Solution

Intervention Type: DRUG

Subcutaneous infusion with IGSC, 20%

Interventions

Immune Globulin Intravenous (Human), 10% Solution

Intravenous infusion with IGIV, 10%

Intervention Type: BIOLOGICAL

Immune Globulin Subcutaneous (Human), 20% Solution

Subcutaneous infusion with IGSC, 20%

Intervention Type: DRUG

Other Intervention Names

IGIV; 10%; IGSC; 20%

Eligibility Criteria

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

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

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baxalta now part of Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

University of California, Irvine

Irvine, California, United States

IMMUNOe International Research Centers

Centennial, Colorado, United States

Allergy Associates of the Palm Beaches

North Palm Beach, Florida, United States

Emory University

Atlanta, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

Family Allergy and Asthma Research Institute

Louisville, Kentucky, United States

Children's Hospital New Orleans- LSUHSC School of Medicine

New Orleans, Louisiana, United States

Midwest Immunology Clinical and Infusion Center

Plymouth, Minnesota, United States

SSM Cardinal Glennon Children's Medical Center

St Louis, Missouri, United States

Montefiore Medical Center Division of Allergy/Immunology

The Bronx, New York, United States

Oklahoma Institute of Allergy and Asthma Clinical Research

Oklahoma City, Oklahoma, United States

Vital Prospects Clinical Research Institute, PC

Tulsa, Oklahoma, United States

Dallas Allergy Immunology Research

Dallas, Texas, United States

Allergy Asthma and Immunology Clinic PA

Irving, Texas, United States

Rocky Mountain Asthma/Allergy/Immunology

Layton, Utah, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Centre Hospitalier Universitaire (CHU) Sainte-Justine

Montreal, Quebec, Canada

Montreal Children's Hospital- McGill University health Center

Montreal, Quebec, Canada

Countries

United States; Canada

References

Al-Herz W, Bousfiha A, Casanova JL, Chapel H, Conley ME, Cunningham-Rundles C, Etzioni A, Fischer A, Franco JL, Geha RS, Hammarstrom 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.

Reference Type: BACKGROUND

PMID: 22566844 (View on PubMed)

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. doi: 10.1006/clim.1999.4799. No abstract available.

Reference Type: BACKGROUND

PMID: 10600329 (View on PubMed)

Li Z, McCoy B, Engl W, Yel L. Steady-State Serum IgG Trough Levels Are Adequate for Pharmacokinetic Assessment in Patients with Immunodeficiencies Receiving Subcutaneous Immune Globulin. J Clin Immunol. 2021 Aug;41(6):1331-1338. doi: 10.1007/s10875-021-00990-z. Epub 2021 May 26.

Reference Type: DERIVED

PMID: 34036490 (View on PubMed)

Suez D, Krivan G, Jolles S, Stein M, Gupta S, Paris K, van Hagen PM, Brodszki N, Engl W, Leibl H, McCoy B, Yel L. Safety and tolerability of subcutaneous immunoglobulin 20% in primary immunodeficiency diseases from two continents. Immunotherapy. 2019 Aug;11(12):1057-1065. doi: 10.2217/imt-2019-0057. Epub 2019 Jul 3.

Reference Type: DERIVED

PMID: 31268374 (View on PubMed)

Gupta S, Stein M, Hussain I, Paris K, Engl W, McCoy B, Rabbat CJ, Yel L. Tolerability of Ig20Gly during onboarding in patients with primary immunodeficiency diseases. Ann Allergy Asthma Immunol. 2019 Sep;123(3):271-279.e1. doi: 10.1016/j.anai.2019.06.004. Epub 2019 Jun 20.

Reference Type: DERIVED

PMID: 31228628 (View on PubMed)

Paris K, Haddad E, Borte M, Brodszki N, Derfalvi B, Marodi L, Hussain I, Darter A, Engl W, Leibl H, McCoy B, Yel L. Tolerability of subcutaneous immunoglobulin 20%, Ig20Gly, in pediatric patients with primary immunodeficiencies. Immunotherapy. 2019 Apr;11(5):397-406. doi: 10.2217/imt-2018-0088. Epub 2019 Jan 9.

Reference Type: DERIVED

PMID: 30626238 (View on PubMed)

Suez D, Stein M, Gupta S, Hussain I, Melamed I, Paris K, Darter A, Bourgeois C, Fritsch S, Leibl H, McCoy B, Gelmont D, Yel L. Efficacy, Safety, and Pharmacokinetics of a Novel Human Immune Globulin Subcutaneous, 20 % in Patients with Primary Immunodeficiency Diseases in North America. J Clin Immunol. 2016 Oct;36(7):700-12. doi: 10.1007/s10875-016-0327-9. Epub 2016 Aug 31.

Reference Type: DERIVED

PMID: 27582171 (View on PubMed)

Other Identifiers

170904

Identifier Type: -

Identifier Source: org_study_id