Assessment of the safety of Immunoglobulin and recombinant human hylaluronidase in the treatment of patients with primary immunodeficiency

• Register: EUCTR
• Last refreshed on: 24 June 2013
• Main ID: EUCTR2012-000481-38-GB
• Date of registration: 26/04/2012
• Prospective Registration: Yes
• Primary sponsor: Baxter Innovations GmbH
• Public title: Assessment of the safety of Immunoglobulin and recombinant human hylaluronidase in the treatment of patients with primary immunodeficiency
• Scientific title: Tolerability, Safety and Product Administration Evaluation of rHuPH20 Facilitated Subcutaneous Treatment with Immune Globulin (Human), 10% in Subjects with Primary Immunodeficiency Diseases – A Study in Europe - Tolerability and Safety of IG, 10% with rHuPH20 in PIDD
• Date of first enrolment: 28/06/2012
• Target sample size: 40
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000481-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Belgium, Czech Republic, Germany, Italy, Netherlands, Sweden, Switzerland, United Kingdom

Contacts

• Name: Medical Director
• Affiliation: Baxter Healthcare Corporation

• Name: Medical Director
• Affiliation: Baxter Healthcare Corporation

Key inclusion & exclusion criteria

Inclusion criteria:
1. 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. prior to enrollment. The diagnosis must be confirmed by the Medical Director prior to first treatment with IP in the study.
2. Subject is 2 years or older at the time of screening
3. Subject has been receiving a consistent dose of IgG with a non-Baxter product (Hizentra SC or a non-Baxter product IV), or Subcuvia SC, 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 an equivalent of 300 mg/kg BW every 4 weeks at a dosing frequency as follows:
a) For IV treatment prior to the study: at mean intervals of 3 or 4 weeks (± 3 days) or
b) For SC treatment prior to the study: at mean intervals of approximately 1 or 2 weeks (± 2 days)
4. Subject has a serum trough level of IgG >5 g/L at screening
5. Subject has not had a serious bacterial infection within the 3 months prior to screening.
Are the trial subjects under 18? yes
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Subject has a known history of or is positive at screening for one or more of the following: HBsAg, polymerase chain reaction (PCR) for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1/2
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):
a) Persistent alanine aminotransferase (ALT) and aspartate amino transferase (AST) >2.5 times the upper limit of normal for the testing laboratory
b) Persistent severe neutropenia (defined as an absolute neutrophil count [ANC] = 500/mm3)
3. Subject has creatinine clearance (CLcr) value that is <60% of normal for age and gender either measured, or calculated according to the formula below:
For males:
(140 – age (years)) * body weight (kg)
CLcr = ----------------------------------------------
72 * serum creatinine (mg/dL)
For females:
(140 – age (years)) * body weight (kg) * 0.85
CLcr = -----------------------------------------------------
72 * serum creatinine (mg/dL)
4. 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
5. 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
6. Subject has abnormal protein loss (protein losing enteropathy, nephritic syndrome)
7. Subject has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site
8. 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
9. Subject has immunoglobulin A (IgA) deficiency (IgA less than 0.07g/L) and known anti IgA antibodies
10. Subject has a known allergy to hyaluronidase
11. 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
12. Subject has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening
13. 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
14. Subject has total protein >9 g/dL or myeloma, or macroglobulinemia (IgM) or paraproteinemia
15. Subject has severe dermatitis that would preclude adequate sites for safe product administration



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Primary Immunodeficiency Diseases
MedDRA version: 14.1 Level: HLT Classification code 10036700 Term: Primary immunodeficiency syndromes System Organ Class: 10021428 - Immune system disorders

Intervention(s)

Trade Name: KIOVIG 100 mg/ml solution for infusion
Product Name: Human normal immunoglobulin
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: HUMAN NORMAL IMMUNOGLOBULIN
Other descriptive name: HUMAN NORMAL IMMUNOGLOBULIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Trade Name: KIOVIG 100 mg/ml solution for infusion
Product Name: Human normal immunoglobulin
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: HUMAN NORMAL IMMUNOGLOBULIN
Other descriptive name: HUMAN NORMAL IMMUNOGLOBULIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Product Name: Recombinant Human Hyaluronidase (rHuPH20)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: HYALURONIDASE
CAS Number: 757971-58-7
Other descriptive name: 36-482-Hyaluronoglucosaminidase PH20 (rHuPH20)
Concentration unit: U/ml unit(s)/millilitre
Concentration type: equal
Concentration number: 160-

Primary Outcome(s)

Main Objective: Tolerability of rHuPH20 facilitated SC treatment of IG, 10% treatment in subjects with PIDD who were on intravenous (IV) or subcutaneous (SC) treatment before the study.

Secondary Objective: Safety, product administration, IgG trough levels, and further tolerability assessments.

Primary end point(s): Primary outcome measure:
Percent of infusions tolerated.

Timepoint(s) of evaluation of this end point: 2-, 3- and 4-week intervals.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 2-, 3- and 4-week intervals.

Secondary end point(s): Secondary outcome measures:

TOLERABILITY AND SAFETY
1. Proportion of subjects who achieve a treatment interval of 2 weeks in Epoch 2 and of 3 or 4 weeks in Epoch 3 (Study Arms 2 or 3 only)
2. Proportion of subjects who maintain a treatment interval of 2 weeks in Epoch 2 and of 2, 3 or 4 weeks in Epoch 3 for a minimum of 8 weeks
3. Number and rate per subject and per infusion (excluding infections) of related systemic adverse events (AEs)
4. Number and rate per subject and per infusion (excluding infections) of related local AEs
5. Number and rate per subject and per infusion (excluding infections) of all AEs
6. Number of subjects who develop neutralizing antibodies to rHuPH20

EFFICACY
Trough levels of IgG

PRODUCT ADMINISTRATION
1. Infusions
a) Duration of infusion and mean rate of infusion
b) Maximum infusion rate achieved
c) Percent of subjects who achieve maximum allowable infusion rate per protocol for any/all infusions
d) Number of infusions (as training) prior to independent self-infusion (subject/caregiver)
e) Number of subjects/caregivers approved by investigator for independent self-infusion
2. Proportion of subjects who prefer IG, 10% and rHuPH20 to previous IgG treatment (to be measured at the End-of-Study visit)

FURTHER KEY VARIABLES
- Efficacy
- Quality of Life
- Treatment Satisfaction Questionnaire
- Treatment Preference Questionnaire
- Product Administration

Secondary ID(s)

161102

Source(s) of Monetary Support

Baxter Innovations GmbH