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A Study to Evaluate the Safety and Pharmacology of Subcutaneous Administration of CINRYZE With Recombinant Human Hyaluronidase

Sponsor
Shire (Industry)
Overall Status
Completed
CT.gov ID
NCT01426763
Collaborator
Halozyme Therapeutics (Industry)
12
Enrollment
4
Locations
2
Arms
2.5
Actual Duration (Months)
3
Patients Per Site
1.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objectives of the study are to:

  1. Evaluate the safety and tolerability of subcutaneously administered CINRYZE with recombinant human hyaluronidase (rHuPH20) in subjects with hereditary angioedema (HAE) who previously participated in CINRYZE Study 0624-200 (NCT01095497)

  2. Characterize the pharmacokinetics and pharmacodynamics of subcutaneously administered CINRYZE with rHuPH20

  3. Assess the immunogenicity of CINRYZE following subcutaneous (SC) administration of CINRYZE with rHuPH20

Condition or Disease Intervention/Treatment Phase
  • Biological: CINRYZE with rHuPH20
 Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
12 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
An Open-label Multiple-dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Administration of CINRYZE® (C1 Esterase Inhibitor [Human]) With Recombinant Human Hyaluronidase (rHuPH20) in Subjects With Hereditary Angioedema
Actual Study Start Date :
Sep 12, 2011
Actual Primary Completion Date :
Nov 28, 2011
Actual Study Completion Date :
Nov 28, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: SC CINRYZE with rHuPH20 Dose Level 1

Subcutaneous injection of 1000 Units of CINRYZE with 20,000 Units of rHuPH20 twice weekly for two weeks

Biological: CINRYZE with rHuPH20
Other Names:
  • C1 esterase inhibitor (human)
  • Recombinant human hyaluronidase

    		•
    Experimental: SC CINRYZE with rHuPH20 Dose Level 2

    Subcutaneous injection of 2000 Units of CINRYZE with 40,000 Units of rHuPH20 twice weekly for two weeks

    Biological: CINRYZE with rHuPH20
    Other Names:
  • C1 esterase inhibitor (human)
  • Recombinant human hyaluronidase

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Incidence and Severity of Adverse Events, Number of Participants With Local Injection Site Reactions, and Number of Participants Who Discontinue Study Drug or Withdraw From the Study [18 days]

    Secondary Outcome Measures

    1. Mean Change C1 Inhibitor (C1INH) [18 days]

      Mean Change in Baseline in Observed Plasma Concentration of C1 Inhibitor (C1INH) Antigen. Baseline-corrected concentrations were derived by subtracting the observed pre-dose concentrations on Day 1 of each treatment period from each observed concentration.

    2. Mean Change C4 Compliment [18 days]

      Mean Change in Baseline in Observed Plasma Concentration of C4 Compliment. Baseline-corrected concentrations were derived by subtracting the observed pre-dose concentrations on Day 1 of each treatment period from each observed concentration.

    3. Number of Subjects With C1 INH Antibodies [Day 1 (pre-dose), Day 18 (168 h post Dose 4), and 30 (±2) days after the last dose of study drug (Dose 4)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    To be eligible for this protocol, a subject must:

    1. Provide informed consent/assent, as appropriate.

    2. Have previously participated in CINRYZE Study 0624-200 and completed the subcutaneous therapy period in that study.

    3. During the 3 consecutive months prior to screening, have a history of less than 1 HAE attack per month (average) that required treatment with C1 INH therapy or other blood products.

    4. Agree to avoid his/her known HAE triggers during the study to the best of his/her ability.

    Exclusion Criteria:
    To be eligible for this protocol, a subject must not:

    1. Have received C1 INH therapy or any blood products for treatment or prevention of an HAE attack within 14 days prior to the first dose of study drug.

    2. Have received any ecallantide (Kalbitor), icatibant (Firazyr), or antifibrinolytics (e.g., tranexamic acid) within 14 days prior to the first dose of study drug.

    3. Have any change (start, stop, or change in dose) in androgen therapy (e.g., danazol, oxandrolone, stanozolol, testosterone) within 14 days prior to the first dose of study drug.

    4. If female, have started taking or changed the dose of any hormonal contraceptive regimen or hormone replacement therapy (i.e., estrogen/progestin containing products) within 3 months prior to the first dose of study drug.

    5. Have a history of abnormal blood clotting.

    6. Have a history of allergic reaction to products containing C1 INH or other blood products.

    7. Have a known allergy to hyaluronidase or any other ingredient in rHuPH20.

    8. Be pregnant or breastfeeding.

    9. Have received an investigational study drug within 30 days prior to the first dose of study drug.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 ViroPharma Investigational Site Scottsdale Arizona United States 85251
    2 ViroPharma Investigational Site Walnut Creek California United States 94598
    3 ViroPharma Investigational Site Atlanta Georgia United States 30342
    4 ViroPharma Investigational Site Dallas Texas United States 75231

    Sponsors and Collaborators

    • Shire
    • Halozyme Therapeutics

    Investigators

    • Study Director: Study Director, Takeda

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Shire
    ClinicalTrials.gov Identifier:
    NCT01426763
    Other Study ID Numbers:
    • 0624-204
    • SPD616-204
    First Posted:
    Aug 31, 2011
    Last Update Posted:
    Jul 19, 2021
    Last Verified:
    Jun 1, 2021
    Keywords provided by Shire
    HAE
    C1 esterase inhibitor
    C1 INH
    Subcutaneous
    hyaluronidase
    rHuPH20
    Additional relevant MeSH terms:
    Angioedema
    Angioedemas, Hereditary
    Complement C1s
    Complement C1 Inhibitor Protein
    Complement C1 Inactivator Proteins

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 SC CINRYZE With rHuPH20 Dose Level 2
    Arm/Group Description SC injection of 1000 Units of CINRYZE with ~20,000 Units of rHuPH20 twice weekly for two weeks SC injection of 2000 Units of CINRYZE with ~40,000 Units of rHuPH20 twice weekly for two weeks
    Period Title: Overall Study
    STARTED 6 6
    COMPLETED 6 6
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 SC CINRYZE With rHuPH20 Dose Level 2 Total
    Arm/Group Description SC injection of 1000 Units of CINRYZE with ~20,000 Units of rHuPH20 twice weekly for two weeks SC injection of 2000 Units of CINRYZE with ~40,000 Units of rHuPH20 twice weekly for two weeks Total of all reporting groups
    Overall Participants 6 6 12
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    31.5
    (7.79)
    33.7
    (10.27)
    32.6
    (8.76)
    Sex: Female, Male (Count of Participants)
    Female
    3
    50%
    4
    66.7%
    7
    58.3%
    Male
    3
    50%
    2
    33.3%
    5
    41.7%

    Outcome Measures

    1. Primary Outcome
    Title Incidence and Severity of Adverse Events, Number of Participants With Local Injection Site Reactions, and Number of Participants Who Discontinue Study Drug or Withdraw From the Study
    Description
    Time Frame 18 days

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 SC CINRYZE With rHuPH20 Dose Level 2
    Arm/Group Description SC injection of 1000 Units of CINRYZE with ~20,000 Units of rHuPH20 twice weekly for two weeks SC injection of 2000 Units of CINRYZE with ~40,000 Units of rHuPH20 twice weekly for two weeks
    Measure Participants 6 6
    Number of participants with adverse events
    6
    100%
    5
    83.3%
    Number of participants with injection site reactions
    6
    100%
    5
    83.3%
    Number of participants who discontinued study drug
    0
    0%
    0
    0%
    Number of participants who withdrew from the study
    0
    0%
    0
    0%
    2. Secondary Outcome
    Title Mean Change C1 Inhibitor (C1INH)
    Description Mean Change in Baseline in Observed Plasma Concentration of C1 Inhibitor (C1INH) Antigen. Baseline-corrected concentrations were derived by subtracting the observed pre-dose concentrations on Day 1 of each treatment period from each observed concentration.
    Time Frame 18 days

    Outcome Measure Data

    Analysis Population Description
    Intent to Treat
    Arm/Group Title Subcutaneous (SC) With Recombinant Human Hyaluronidase ph20 (rHuPH20) CYNRYZE Dose 1 SC CINRYZE With rHuPH20 Dose Level 2
    Arm/Group Description 1000 Units of SC CYNRYZE with ~20,000 Units of rHuPH20 twice weekly for two weeks SC injection of 2000 Units of CINRYZE with ~40,000 Units of rHuPH20 twice weekly for two weeks
    Measure Participants 6 6
    0 Hour (h)
    0.0248
    (0.0565)
    0.00483
    (0.00904)
    1 hour (h) post Dose 1
    0.0273
    (0.065)
    0.00383
    (0.00417)
    2 h post Dose 1
    0.0302
    (0.0637)
    0.008
    (0.0123)
    3 h post Dose 1
    0.0275
    (0.0602)
    0.0095
    (0.00729)
    4 h post Dose 1
    0.0382
    (0.0652)
    0.011
    (0.00537)
    6 h post Dose 1
    0.0398
    (0.0599)
    0.020
    (0.00678)
    8 h post Dose 1
    0.0455
    (0.0624)
    0.031
    (0.0154)
    24 h post Dose 1
    0.0625
    (0.0728)
    0.0612
    (0.0212)
    48 h post Dose 1
    0.0665
    (0.0749)
    0.0603
    (0.0213)
    Pre-Dose 2
    0.0243
    (0.0234)
    0.0507
    (0.0168)
    1 h post Dose 2
    0.0387
    (0.0749)
    0.00833
    (0.00852)
    120 h post Dose 1
    0.020
    (0.00883)
    0.0388
    (0.0132)
    Pre-Dose 3
    0.0288
    (0.0644)
    0.00833
    (0.0095)
    1 h post Dose 3
    0.00217
    (0.00271)
    0.004
    (0.00405)
    Pre-Dose 4
    0.006
    (0.0119)
    0.0128
    (0.00854)
    1 h post Dose 4
    0.0193
    (0.012)
    0.033
    (0.0196)
    2 h post Dose 4
    0.0233
    (0.0126)
    0.0377
    (0.021)
    3 h post Dose 4
    0.0238
    (0.012)
    0.0333
    (0.0163)
    4 h post Dose 4
    0.0257
    (0.0142)
    0.037
    (0.0215)
    6 h post Dose 4
    0.0298
    (0.0124)
    0.039
    (0.025)
    8 h post Dose 4
    0.0354
    (0.0118)
    0.0397
    (0.0157)
    24 h post Dose 4
    0.0347
    (0.018)
    0.0623
    (0.0207)
    48 h post Dose 4
    0.0273
    (0.0171)
    0.0562
    (0.00906)
    72 h post Dose 4
    0.0167
    (0.0185)
    0.046
    (0.0106)
    120 h post Dose 4
    0.0165
    (0.0214)
    0.0157
    (0.00797)
    168 h post Dose 4
    0.00933
    (0.0201)
    0.0382
    (0.0935)
    3. Secondary Outcome
    Title Mean Change C4 Compliment
    Description Mean Change in Baseline in Observed Plasma Concentration of C4 Compliment. Baseline-corrected concentrations were derived by subtracting the observed pre-dose concentrations on Day 1 of each treatment period from each observed concentration.
    Time Frame 18 days

    Outcome Measure Data

    Analysis Population Description
    Intent to Treat
    Arm/Group Title Subcutaneous (SC) With Recombinant Human Hyaluronidase ph20 (rHuPH20) CYNRYZE Dose 1 SC CINRYZE With rHuPH20 Dose Level 2
    Arm/Group Description 1000 Units of SC CYNRYZE with ~20,000 Units of rHuPH20 twice weekly for two weeks SC injection of 2000 Units of CINRYZE with ~40,000 Units of rHuPH20 twice weekly for two weeks
    Measure Participants 6 6
    0 Hour (h)
    9.00
    (15.4)
    13.3
    (14.4)
    1 hour (h) post Dose 1
    11.0
    (14.3)
    10.3
    (21.4)
    2 h post Dose 1
    11.3
    (13.8)
    11.0
    (18.7)
    3 h post Dose 1
    10.2
    (11.7)
    11.5
    (17.6)
    4 h post Dose 1
    11.5
    (13.6)
    13.2
    (16.8)
    6 h post Dose 1
    15.7
    (14.2)
    14.0
    (18.1)
    8 h post Dose 1
    16.3
    (16.6)
    22.5
    (29.1)
    24 h post Dose 1
    25.0
    (15.6)
    30.5
    (19.5)
    48 h post Dose 1
    37.4
    (23.1)
    49.8
    (24.3)
    Pre-Dose 2
    24.3
    (14.5)
    53.3
    (23.2)
    1 h post Dose 2
    37.5
    (21.6)
    53.2
    (22.6)
    120 h post Dose 1
    35.6
    (22.6)
    70.8
    (28.4)
    Pre-Dose 3
    29.0
    (19.1)
    66.3
    (47.0)
    1 h post Dose 3
    32.5
    (18.7)
    69.3
    (50.5)
    Pre-Dose 4
    32.0
    (18.4)
    62.5
    (54.2)
    1 h post Dose 4
    30.2
    (18.8)
    57.3
    (53.7)
    2 h post Dose 4
    33.3
    (24.5)
    59.7
    (52.5)
    3 h post Dose 4
    34.3
    (17.9)
    53.3
    (46.2)
    4 h post Dose 4
    34.8
    (22.9)
    63.3
    (56.5)
    6 h post Dose 4
    36.3
    (21.6)
    59.7
    (46.4)
    8 h post Dose 4
    33.6
    (20.3)
    56.5
    (48.4)
    24 h post Dose 4
    37.8
    (23.0)
    64.7
    (52.4)
    48 h post Dose 4
    33.0
    (22.4)
    65.7
    (47.0)
    72 h post Dose 4
    23.3
    (20.6)
    72.2
    (57.5)
    120 h post Dose 4
    16.8
    (15.5)
    58.7
    (46.4)
    168 h post Dose 4
    19.0
    (18.4)
    44.8
    (46.0)
    4. Secondary Outcome
    Title Number of Subjects With C1 INH Antibodies
    Description
    Time Frame Day 1 (pre-dose), Day 18 (168 h post Dose 4), and 30 (±2) days after the last dose of study drug (Dose 4)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Subcutaneous (SC) With Recombinant Human Hyaluronidase ph20 (rHuPH20) CYNRYZE Dose 1 SC CINRYZE With rHuPH20 Dose Level 2
    Arm/Group Description SC injection of 1000 Units of CINRYZE with ~20,000 Units of rHuPH20 twice weekly for two weeks SC injection of 2000 Units of CINRYZE with ~40,000 Units of rHuPH20 twice weekly for two weeks
    Measure Participants 6 6
    Day 1 (pre-dose)
    0
    0%
    0
    0%
    Day 18 (168 h post Dose 4)
    0
    0%
    0
    0%
    30 (±2) days after the last dose of study drug (Dose 4)
    0
    0%
    0
    0%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 SC CINRYZE With rHuPH20 Dose Level 2
    Arm/Group Description SC injection of 1000 Units of CINRYZE with ~20,000 Units of rHuPH20 twice weekly for two weeks SC injection of 2000 Units of CINRYZE with ~40,000 Units of rHuPH20 twice weekly for two weeks
    All Cause Mortality
    Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 SC CINRYZE With rHuPH20 Dose Level 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 SC CINRYZE With rHuPH20 Dose Level 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/6 (0%) 0/6 (0%)
    Other (Not Including Serious) Adverse Events
    Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 SC CINRYZE With rHuPH20 Dose Level 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/6 (100%) 5/6 (83.3%)
    General disorders
    Injection site erythema 5/6 (83.3%) 5/6 (83.3%)
    Injection site hemorrhage 1/6 (16.7%) 0/6 (0%)
    Injection site induration 0/6 (0%) 1/6 (16.7%)
    Injection site edema 1/6 (16.7%) 0/6 (0%)
    Injection site pain 4/6 (66.7%) 1/6 (16.7%)
    Injection site pruritus 1/6 (16.7%) 0/6 (0%)
    Injection site swelling 2/6 (33.3%) 0/6 (0%)
    Infections and infestations
    Upper respiratory tract infection 1/6 (16.7%) 0/6 (0%)
    Urinary tract infection 0/6 (0%) 1/6 (16.7%)
    Musculoskeletal and connective tissue disorders
    Pain in extremity 0/6 (0%) 1/6 (16.7%)
    Nervous system disorders
    Headache 0/6 (0%) 1/6 (16.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Clinical Study Agreement. Most restrictive provision - PI will not publish results until after first of: multicenter publication is published or 24 months from study end. Thereafter, PI may publish his results. PI must provide copy of proposed publication to Sponsor for pre-review. If Sponsor requests, PI must delete Sponsor confidential information before publication and/or delay publication for 60 days so Sponsor can file for patents or take other action to protect its patent rights.

    Results Point of Contact

    Name/Title Study Director
    Organization Shire
    Phone +1 866 842 5335
    Email ClinicalTransparency@shire.com
    Responsible Party:
    Shire
    ClinicalTrials.gov Identifier:
    NCT01426763
    Other Study ID Numbers:
    • 0624-204
    • SPD616-204
    First Posted:
    Aug 31, 2011
    Last Update Posted:
    Jul 19, 2021
    Last Verified:
    Jun 1, 2021