Gammagard Liquid and rHuPH20 in PID

NCT00814320 | Completed Phase 3 Results

• 1 other identifier: 160603
• Study Type: interventional
• Target: 89
• Locations: 2 countries
• Sites: 14

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)

Outcome Measures

Primary Outcomes (1)

• Validated Acute Serious Bacterial Infection (VASBI) Rate

  Serious acute bacterial infections include bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess that are caused by a recognized bacterial pathogen. VASBI rate is the mean number of VASBIs per participant per year, recorded for SC Administration of IGIV, 10%, with rHuPH20 after ramp-up, only. The mean number of VASBIs per participant per year and the 99% upper confidence limit for the acute serious bacterial infection rate were calculated using a Poisson model to account for the length of the observation periods per participant.

  Throughout the study period (17 months)

Secondary Outcomes (65)

• Bioavailability (AUC) of IgG After Administration of IGIV, 10% Given Via IV or SC With rHuPH20 in Participants ≥12 Years

  PK AUC evaluations: (IV: before infusion #4 [for 3-week treatment interval] or infusion #3 [for 4-week treatment interval];SC: before last SC infusion) 60 minutes pre-infusion up to 28 days (+/-2 days) post-infusion

• Bioavailability (Trough Levels) of IgG After Administration of IGIV, 10% Given Via IV or SC With rHuPH20 in Participants Aged 2 to < 12 Years

  IgG trough levels measured at baseline and on day of each 3- or 4-week infusion for infusion for IV and SC (except during ramp-up for SC) and at end of study visit

• Bioavailability (AUC) of IgG After SC Administration of IGIV, 10%, Given With and Without rHuPH20

  PK: 160603 (IV: before infusion (inf.) #4 [3-week treatment interval] or inf. #3 [4-week treatment interval];SC: before last SC inf.) 1 hour pre-inf. ≤28 days (+/-2 days) post-inf.; 160601- 1 hour pre-inf. (before inf. #8) ≤7 days (+/-1 day) post-inf.

• Annual Rate of All Infections Per Participant

  Throughout the study period (17 months)

• Trough Levels of IgG After Administration of IGIV, 10% Given Via IV or SC With rHuPH20

  IgG trough levels measured at baseline and on day of each 3- or 4-week infusion for IV and SC (except during ramp up for SC) and at end of study visit.

Study Arms (2)

1

EXPERIMENTAL

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

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

2

EXPERIMENTAL

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

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

Interventions

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

Also known as: HYQVIA

1

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:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (14)

Unknown Facility

Cypress, California, United States

Location

Unknown Facility

Irvine, California, United States

Location

Unknown Facility

Los Angeles, California, United States

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Unknown Facility

San Francisco, California, United States

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Unknown Facility

Centennial, Colorado, United States

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Unknown Facility

North Palm Beach, Florida, United States

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Unknown Facility

Atlanta, Georgia, United States

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Unknown Facility

Hinsdale, Illinois, United States

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Unknown Facility

Omaha, Nebraska, United States

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Unknown Facility

The Bronx, New York, United States

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Unknown Facility

Dallas, Texas, United States

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Unknown Facility

Galveston, Texas, United States

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Unknown Facility

Milwaukee, Wisconsin, United States

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Unknown Facility

Vancouver, British Columbia, Canada

Location

Related Publications (3)

• 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.

  PMID: 27220317 RESULT

• 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.

  PMID: 22846381 RESULT

• 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.

  PMID: 34931880 DERIVED

MeSH Terms

Conditions

Primary Immunodeficiency Diseases

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Shire

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2008
• First Posted: December 24, 2008
• Study Start: December 18, 2008
• Primary Completion: November 11, 2010
• Study Completion: November 11, 2010
• Last Updated: May 19, 2021
• Results First Posted: December 3, 2015

Record last verified: 2021-04

Locations

US (13); CA (1)