Gammagard Liquid and rHuPH20 in PID

NCT ID: NCT00814320

Last Updated: 2021-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-12-18
• Study Completion Date: 2010-11-11

Brief Summary

The purpose of the study is to develop a subcutaneous treatment option for participants with Primary Immunodeficiency Diseases (PID) that allows an administration of Immune Globulin Intravenous (Human), 10% at the same frequency as IV administration.

Conditions

Primary Immunodeficiency Diseases (PID)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Efficacy and tolerability of subcutaneous (SC) infusions of immune globulin intravenous (IGIV), 10% with hyaluronidase (rHuPH20) after ramp-up

Group Type: EXPERIMENTAL

Recombinant human hyaluronidase (rHuPH20)+ immune globulin intravenous (IGIV)

Intervention Type: BIOLOGICAL

Comprises subjects previously participating in Study 160601, who now only complete Study Epoch 2 (subcutaneous [SC] infusions) as bioavailability/exposure for intravenous (IV) treatment was already obtained in Study 160601.

Study Epoch 2: Dose (calculated) of rHuPH20 followed by dose (calculated) of IGIV, 10% by SC infusion. Treatment intervals and doses are to be increased as defined, until treatment interval is the same as the pre-study treatment interval for IV treatment (ramp-up).

2

Pharmacokinetics of intravenous (IV) infusions of immune globulin intravenous (IGIV), 10% and efficacy and tolerability of subcutaneous (SC) infusions of immune globulin intravenous (IGIV), 10% with hyaluronidase (rHuPH20) after ramp-up

Group Type: EXPERIMENTAL

Recombinant human hyaluronidase (rHuPH20)+ immune globulin intravenous (IGIV)

Intervention Type: BIOLOGICAL

Comprises all other subjects.

Study Epoch 1: IV infusion of IGIV, 10% (same dose and frequency as pre-study) to determine pharmacokinetics.

Study Epoch 2: Dose (calculated) of rHuPH20 followed by dose (calculated) of IGIV, 10% by SC infusion. Treatment intervals and doses are to be increased as defined, until treatment interval is the same as the pre-study treatment interval for IV treatment (ramp-up).

Interventions

Recombinant human hyaluronidase (rHuPH20)+ immune globulin intravenous (IGIV)

Comprises subjects previously participating in Study 160601, who now only complete Study Epoch 2 (subcutaneous [SC] infusions) as bioavailability/exposure for intravenous (IV) treatment was already obtained in Study 160601.

Study Epoch 2: Dose (calculated) of rHuPH20 followed by dose (calculated) of IGIV, 10% by SC infusion. Treatment intervals and doses are to be increased as defined, until treatment interval is the same as the pre-study treatment interval for IV treatment (ramp-up).

Intervention Type: BIOLOGICAL

Recombinant human hyaluronidase (rHuPH20)+ immune globulin intravenous (IGIV)

Comprises all other subjects.

Study Epoch 1: IV infusion of IGIV, 10% (same dose and frequency as pre-study) to determine pharmacokinetics.

Study Epoch 2: Dose (calculated) of rHuPH20 followed by dose (calculated) of IGIV, 10% by SC infusion. Treatment intervals and doses are to be increased as defined, until treatment interval is the same as the pre-study treatment interval for IV treatment (ramp-up).

Intervention Type: BIOLOGICAL

Other Intervention Names

HYQVIA

Eligibility Criteria

Inclusion Criteria

• Participant is 2 years or older at the time of screening
• Written informed consent obtained from either the participant or the participant's legally acceptable representative prior to any study-related procedures and study product administration
• Participant has been diagnosed with a PID disorder requiring antibody replacement as defined by WHO criteria
• Participant has completed or is about to complete Baxter Clinical Study Protocol No. 160601 or has been receiving a regular IGIV-treatment at mean intervals of 21 ± 3 days or 28 ± 3 days, or SC at mean intervals of 5 to 16 days, over a period of at least 3 months prior to enrollment at a minimum dose of 300 mg/kg BW/4 weeks
• Participant has a serum trough level of IgG > 4.5 g/L at the last documented determination
• If female of childbearing potential, participant presents with a negative urine pregnancy test and agrees to employ adequate birth control measures for the duration of the study
• Participant is willing and able to comply with the requirements of the protocol

Exclusion Criteria

• Participant has a known history of or is positive at enrollment or 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
• Participant has levels of alanine aminotransferase (ALT) or aspartate amino transferase (AST) > 2.5 times the upper limit of normal for the testing laboratory
• Participant has persistent severe neutropenia (defined as an absolute neutrophil count [ANC] <= 500/mm3)
• Participant has creatinine clearance (CLcr) values, calculated according to the formula below, which are < 60% of normal for age and gender for males: CLcr = [(140 - Age(years)) * (body weight (kg))] / [72 * (serum creatinine (mg/dL))] for females: CLcr = [(140 - Age(years)) * (body weight(kg)) * 0.85] / [72 * (serum creatinine (mg/dL))]
• Participant has been diagnosed with, or has a malignancy (other than adequately treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix) within the last 12 months prior to enrollment; participants treated with immunosuppressive chemotherapeutic agents during this period are excluded
• Participant has a history of thrombotic episodes (including deep vein thrombosis, myocardial infarction, cerebrovascular accident, pulmonary embolism) within the last 12 months
• Participant has abnormal protein loss (protein losing enteropathy, nephrotic syndrome)
• Participant has anemia that would preclude phlebotomy for laboratory studies
• Participant has received any blood or blood product other than an IGIV, SC immunoglobulin, immune serum globulin (ISG) preparation, or albumin within the 6 months prior to enrollment
• Participant has an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following IGIV, SC immunoglobulin, and/or ISG infusions
• Participant has immunoglobulin A (IgA) deficiency and known anti IgA antibodies
• Participant is on preventative (prophylactic) antibiotics and cannot stop antibiotics at the time of enrollment
• Participant has active infection who started on antibiotic therapy for the treatment of infection within 7 days prior to screening
• Participant has a bleeding disorder or is on anti-coagulation therapy that results in a platelet count less than 20,000/μL or International Normalized Ration (INR) > 2X control, or who, in the opinion of the investigator would be at significant risk of increased bleeding or bruising as a result of SC therapy
• Participant has total protein > 9 g/dL and participants with myeloma, macroglobulinemia (IgM) and paraproteinemia
• Participant has a known allergy to hyaluronidase
• If female, participant is pregnant or lactating at the time of study enrollment
• Participant has participated in another clinical study involving an investigational product (IP) or device within 30 days prior to study enrollment or is scheduled to participate in another clinical study involving an IP or device during the course of this study; exception: Baxter Study No. 160601
• Severe dermatitis that would preclude adequate sites for safe product administration

• 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

Shire

Locations

Cypress, California, United States

Irvine, California, United States

Los Angeles, California, United States

San Francisco, California, United States

Centennial, Colorado, United States

North Palm Beach, Florida, United States

Atlanta, Georgia, United States

Hinsdale, Illinois, United States

Omaha, Nebraska, United States

The Bronx, New York, United States

Dallas, Texas, United States

Galveston, Texas, United States

Milwaukee, Wisconsin, United States

Vancouver, British Columbia, Canada

Countries

United States; Canada

References

Wasserman RL, Melamed I, Stein MR, Engl W, Sharkhawy M, Leibl H, Puck J, Rubinstein A, Kobrynski L, Gupta S, Grant AJ, Ratnayake A, Richmond WG, Church J, Yel L, Gelmont D. Long-Term Tolerability, Safety, and Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Human Immunoglobulin for Primary Immunodeficiency. J Clin Immunol. 2016 Aug;36(6):571-82. doi: 10.1007/s10875-016-0298-x. Epub 2016 May 25.

Reference Type: RESULT

PMID: 27220317 (View on PubMed)

Wasserman RL, Melamed I, Stein MR, Gupta S, Puck J, Engl W, Leibl H, McCoy B, Empson VG, Gelmont D, Schiff RI; IGSC, 10% with rHuPH20 Study Group. Recombinant human hyaluronidase-facilitated subcutaneous infusion of human immunoglobulins for primary immunodeficiency. J Allergy Clin Immunol. 2012 Oct;130(4):951-7.e11. doi: 10.1016/j.jaci.2012.06.021. Epub 2012 Jul 28.

Reference Type: RESULT

PMID: 22846381 (View on PubMed)

Wasserman RL, Gupta S, Stein M, Rabbat CJ, Engl W, Leibl H, Yel L. Infection rates and tolerability of three different immunoglobulin administration modalities in patients with primary immunodeficiency diseases. Immunotherapy. 2022 Mar;14(4):215-224. doi: 10.2217/imt-2021-0256. Epub 2021 Dec 21.

Reference Type: DERIVED

PMID: 34931880 (View on PubMed)

Other Identifiers

160603

Identifier Type: -

Identifier Source: org_study_id