Tolerability and Safety of IGI, 10% With rHuPH20 in PIDD

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01485796
• Date of registration: 02/12/2011
• Prospective Registration: Yes
• Primary sponsor: Baxalta now part of Shire
• Public title: Tolerability and Safety of IGI, 10% With rHuPH20 in PIDD
• Scientific title: Tolerability, Safety and Administration Mode Evaluation of Recombinant Human Hyaluronidase (rHuPH20) Facilitated Subcutaneous Treatment With Immune Globulin Infusion (Human), 10% in Subjects With Primary Immunodeficiency Diseases (PIDD)
• Date of first enrolment: December 29, 2011
• Target sample size: 54
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01485796
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2/Phase 3

Countries of recruitment

United States

Contacts

• Name: Leman Yel, MD
• Affiliation: Baxalta US Inc., now part of Shire

Key inclusion & exclusion criteria

Inclusion Criteria:

- Subject must have a documented diagnosis of a form of primary humoral immunodeficiency
involving a defect in antibody formation and requiring gammaglobulin replacement, as
defined according to the IUIS Scientific Committee 2009 and by diagnostic criteria
according to Conley et al. The diagnosis must be reviewed by the Medical Director
prior to enrollment.

- Subject is 2 years or older at the time of screening.

- Written informed consent is obtained from either the subject or the subject's legally
authorized representative prior to any study-related procedures and study product
administration.

- Subject has been receiving a consistent dose of immunoglobulin G (IgG) with a
non-Baxter product (Gammunex administered IV, Hizentra, or Privigen), administered in
compliance with the respective product information, for a period of at least 3 months
prior to screening. The average minimum pre-study dose over that interval was
equivalent to 300 mg/kg BW/4 weeks and a maximum dose equivalent to 600 mg/kg BW/4
weeks at a dosing frequency as follows:

- For IV treatment prior to the study: at mean intervals of 3 or 4 weeks (+/- 3
days) or

- For SC treatment prior to the study: at mean intervals of approximately 1 or 2
weeks (+/- 2 days).

- Subject has a serum trough level of IgG > 5 g/L at screening.

- Subject has not had a serious bacterial infection within the 3 months prior to
screening.

- If female of childbearing potential, subject presents with a negative pregnancy test
and agrees to employ adequate birth control measures for the duration of the study.

- Subject is willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

- Subject has a 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/mm3).

- Subject has creatinine clearance (CLcr) value that is <60% of normal for age and
gender either measured, or calculated according to a gender-specific formula provided
in the study protocol.

- Subject 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),
unless the disease-free period prior to screening exceeds 5 years

- Subject is receiving anti-coagulation therapy or has a history of thrombotic episodes
(including deep vein thrombosis, myocardial infarction, cerebrovascular accident,
pulmonary embolism) within 12 months prior to screening or a history of thrombophilia.

- Subject has abnormal protein loss (protein losing enteropathy, nephrotic syndrome).

- Subject has anemia that would preclude phlebotomy for laboratory studies, according to
standard practice at the site.

- Subject has an ongoing history of hypersensitivity or persistent reactions (urticaria,
breathing difficulty, severe hypotension, or anaphylaxis) following IV immunoglobulin,
SC immunoglobulin, and/or Immune Serum Globulin (ISG) infusions.

- Subject has immunoglobulin A (IgA) deficiency (IgA less than 0.07g/L) and known anti
IgA antibodies.

- Subject has a known allergy to hyaluronidase.

- Subject is on preventative (prophylactic) systemic antibacterial antibiotics at doses
sufficient to treat or prevent bacterial infections, and cannot stop these antibiotics
at the time of screening.

- Subject has active infection and is receiving antibiotic therapy for the treatment of
infection at the time of screening.

- Subject has a bleeding disorder or 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 SC therapy.

- Subject has total protein > 9 g/dL or myeloma, or macroglobulinemia (IgM) or
paraproteinemia.

- Women of childbearing potential meeting any one of the following criteria:

- Subject presents with a positive pregnancy test

- Subject is breast feeding

- Subject intends to begin nursing during the course of the study

- Subject 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.

- Subject has participated in another clinical study and has been exposed to an
investigational product (IP) or device within 30 days prior to study enrollment
(exception: treatment with immunoglobulin pre-study).

- Subject is scheduled to participate in another (non-Baxter) clinical study involving
an IP or device during the course of the study.

- Subject has severe dermatitis that would preclude adequate sites for safe product
administration.



Age minimum: 2 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Primary Immunodeficiency Diseases (PID)

Intervention(s)

Biological: Immune Globulin Infusion (Human), 10%

Biological: Recombinant human hyaluronidase

Primary Outcome(s)

Number of Related Systemic Adverse Events (Excluding Infections) [Time Frame: 7 months (per subject)]

Rate of Related Systemic Adverse Events (Excluding Infections) Per Infusion [Time Frame: 7 months (per subject)]

Secondary Outcome(s)

Duration of Infusion in Epoch 1 and Epoch 2 [Time Frame: 7 months (per subject)]

Maximum Infusion Rate in Epoch 1 and Epoch 2 [Time Frame: 7 months (per subject)]

Number of Infusion Sites (Needle Sticks) Per Month in Epoch 1 and Epoch 2 [Time Frame: 7 months (per subject)]

Rate of All Adverse Events (Excluding Infections) Per Infusion [Time Frame: 7 months (per subject)]

Trough Levels of Immunoglobulin G (IgG) [Time Frame: 7 months (per subject)]

Number of Infusions Per Month in Epoch 1 and Epoch 2 [Time Frame: 7 months (per subject)]

Rate of Related Local Adverse Events (Excluding Infections) Per Infusion [Time Frame: 7 months (per subject)]

Number of Subjects Who Develop Neutralizing Antibodies to rHuPH20 [Time Frame: 7 months (per subject)]

Proportion of Subjects Who Maintain a Treatment Interval of 3 or 4 Weeks in Epoch 2 for 24 Weeks [Time Frame: 6 months (per subject)]

Number of All Related Adverse Events (Excluding Infections) [Time Frame: 7 months (per subject)]

Number of Related Local Adverse Events (Excluding Infections) [Time Frame: 7 months (per subject)]

Number of Weeks to Reach Final 3 or 4-week Dose Interval [Time Frame: 7 months (per subject)]

Proportion of Subjects Who Achieve a Treatment Interval of 3 or 4 Weeks in Epoch 2 [Time Frame: 6 months (per subject)]

Secondary ID(s)

161101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 24/04/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01485796