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

NCT01218438 | Completed Phase 2 Results

• 1 other identifier: 170904
• Study Type: interventional
• Target: 86
• Locations: 2 countries
• Sites: 18

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)

Outcome Measures

Primary Outcomes (1)

• Rate of Acute Serious Bacterial Infections Per Year (ASBI)

  Annual rate of validated acute serious bacterial infections was calculated using a Poisson model to account for the different lengths of observation per participant. The observation period for each participant starts with the day of the first subcutaneous (SC) infusion in Study Epoch 2 and ends with the day of the End of Study visit.

  1 year

Secondary Outcomes (80)

• Annual Rate of All Infections Per Participant

  1 year

• Annual Rate of Sinus Infections Per Participant

  1 year

• Annual Rate of Fever Episodes Per Participant

  1 year

• Annual Rate of Days Off School/Work or Days Unable to Perform Normal Daily Activities Due to Illness or Infection Per Participant

  1 year

• Annual Rate of Days on Antibiotics Per Participant

  1 year

Study Arms (1)

Study Epochs 1-4

EXPERIMENTAL

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.

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

Interventions

Immune Globulin Intravenous (Human), 10% Solution BIOLOGICAL

Intravenous infusion with IGIV, 10%

Also known as: IGIV, 10%

Study Epochs 1-4

Immune Globulin Subcutaneous (Human), 20% Solution DRUG

Subcutaneous infusion with IGSC, 20%

Also known as: IGSC, 20%

Study Epochs 1-4

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (18)

University of California, Irvine

Irvine, California, 92697, United States

Location

IMMUNOe International Research Centers

Centennial, Colorado, 80112, United States

Location

Allergy Associates of the Palm Beaches

North Palm Beach, Florida, 33408, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Family Allergy and Asthma Research Institute

Louisville, Kentucky, 40215, United States

Location

Children's Hospital New Orleans- LSUHSC School of Medicine

New Orleans, Louisiana, 70118, United States

Location

Midwest Immunology Clinical and Infusion Center

Plymouth, Minnesota, 55446, United States

Location

SSM Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

Location

Montefiore Medical Center Division of Allergy/Immunology

The Bronx, New York, 10461, United States

Location

Oklahoma Institute of Allergy and Asthma Clinical Research

Oklahoma City, Oklahoma, 73131, United States

Location

Vital Prospects Clinical Research Institute, PC

Tulsa, Oklahoma, 74136, United States

Location

Dallas Allergy Immunology Research

Dallas, Texas, 75230, United States

Location

Allergy Asthma and Immunology Clinic PA

Irving, Texas, 75063, United States

Location

Rocky Mountain Asthma/Allergy/Immunology

Layton, Utah, 84041, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Centre Hospitalier Universitaire (CHU) Sainte-Justine

Montreal, Quebec, H3H 1C5, Canada

Location

Montreal Children's Hospital- McGill University health Center

Montreal, Quebec, HEH 1P3, Canada

Location

Related Publications (7)

• 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.

  PMID: 22566844 BACKGROUND

• 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.

  PMID: 10600329 BACKGROUND

• 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.

  PMID: 34036490 DERIVED

• 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.

  PMID: 31268374 DERIVED

• 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.

  PMID: 31228628 DERIVED

• 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.

  PMID: 30626238 DERIVED

• 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.

  PMID: 27582171 DERIVED

MeSH Terms

Conditions

Primary Immunodeficiency Diseases

Interventions

gamma-Globulins; Solutions

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pharmaceutical Preparations

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2010
• First Posted: October 11, 2010
• Study Start: January 28, 2013
• Primary Completion: March 13, 2015
• Study Completion: March 13, 2015
• Last Updated: July 20, 2021
• Results First Posted: February 15, 2017

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

CA (2); US (16)