Hereditary Angioedema
Conditions
Keywords
HAE, C1 esterase inhibitor, C1 INH, Subcutaneous, hyaluronidase, rHuPH20
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
Interventions
BIOLOGICALCINRYZE with rHuPH20
Sponsors
Halozyme Therapeutics
Shire
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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) | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 SC injection of 1000 Units of CINRYZE with \
20,000 Units of rHuPH20 twice weekly for two weeks | 6 |
| SC CINRYZE With rHuPH20 Dose Level 2 SC injection of 2000 Units of CINRYZE with \
40,000 Units of rHuPH20 twice weekly for two weeks | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | SC CINRYZE With rHuPH20 Dose Level 2 | Total |
|---|---|---|---|
| Age, Continuous | 31.5 years STANDARD_DEVIATION 7.79 | 33.7 years STANDARD_DEVIATION 10.27 | 32.6 years STANDARD_DEVIATION 8.76 |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 5 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 |
Outcome results
Primary
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
Time frame: 18 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 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 | Number of participants with adverse events | 6 participants |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 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 | Number of participants with injection site reactions | 6 participants |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 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 | Number of participants who discontinued study drug | 0 participants |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 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 | Number of participants who withdrew from the study | 0 participants |
| SC CINRYZE With rHuPH20 Dose Level 2 | 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 | Number of participants who withdrew from the study | 0 participants |
| SC CINRYZE With rHuPH20 Dose Level 2 | 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 | Number of participants with adverse events | 5 participants |
| SC CINRYZE With rHuPH20 Dose Level 2 | 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 | Number of participants who discontinued study drug | 0 participants |
| SC CINRYZE With rHuPH20 Dose Level 2 | 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 | Number of participants with injection site reactions | 5 participants |
Secondary
Mean Change C1 Inhibitor (C1INH)
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
Population: Intent to Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 3 h post Dose 1 | 0.0275 g/L | Standard Deviation 0.0602 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 6 h post Dose 1 | 0.0398 g/L | Standard Deviation 0.0599 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 4 h post Dose 4 | 0.0257 g/L | Standard Deviation 0.0142 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 48 h post Dose 4 | 0.0273 g/L | Standard Deviation 0.0171 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 0 Hour (h) | 0.0248 g/L | Standard Deviation 0.0565 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 1 hour (h) post Dose 1 | 0.0273 g/L | Standard Deviation 0.065 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 2 h post Dose 1 | 0.0302 g/L | Standard Deviation 0.0637 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 4 h post Dose 1 | 0.0382 g/L | Standard Deviation 0.0652 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 8 h post Dose 1 | 0.0455 g/L | Standard Deviation 0.0624 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 24 h post Dose 1 | 0.0625 g/L | Standard Deviation 0.0728 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 48 h post Dose 1 | 0.0665 g/L | Standard Deviation 0.0749 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | Pre-Dose 2 | 0.0243 g/L | Standard Deviation 0.0234 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 1 h post Dose 2 | 0.0387 g/L | Standard Deviation 0.0749 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 120 h post Dose 1 | 0.020 g/L | Standard Deviation 0.00883 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | Pre-Dose 3 | 0.0288 g/L | Standard Deviation 0.0644 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 1 h post Dose 3 | 0.00217 g/L | Standard Deviation 0.00271 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | Pre-Dose 4 | 0.006 g/L | Standard Deviation 0.0119 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 1 h post Dose 4 | 0.0193 g/L | Standard Deviation 0.012 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 2 h post Dose 4 | 0.0233 g/L | Standard Deviation 0.0126 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 3 h post Dose 4 | 0.0238 g/L | Standard Deviation 0.012 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 6 h post Dose 4 | 0.0298 g/L | Standard Deviation 0.0124 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 8 h post Dose 4 | 0.0354 g/L | Standard Deviation 0.0118 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 24 h post Dose 4 | 0.0347 g/L | Standard Deviation 0.018 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 72 h post Dose 4 | 0.0167 g/L | Standard Deviation 0.0185 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 120 h post Dose 4 | 0.0165 g/L | Standard Deviation 0.0214 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C1 Inhibitor (C1INH) | 168 h post Dose 4 | 0.00933 g/L | Standard Deviation 0.0201 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 3 h post Dose 4 | 0.0333 g/L | Standard Deviation 0.0163 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 120 h post Dose 1 | 0.0388 g/L | Standard Deviation 0.0132 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 120 h post Dose 4 | 0.0157 g/L | Standard Deviation 0.00797 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 4 h post Dose 4 | 0.037 g/L | Standard Deviation 0.0215 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 24 h post Dose 4 | 0.0623 g/L | Standard Deviation 0.0207 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | Pre-Dose 3 | 0.00833 g/L | Standard Deviation 0.0095 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 6 h post Dose 4 | 0.039 g/L | Standard Deviation 0.025 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 0 Hour (h) | 0.00483 g/L | Standard Deviation 0.00904 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 1 h post Dose 3 | 0.004 g/L | Standard Deviation 0.00405 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 1 hour (h) post Dose 1 | 0.00383 g/L | Standard Deviation 0.00417 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 72 h post Dose 4 | 0.046 g/L | Standard Deviation 0.0106 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 2 h post Dose 1 | 0.008 g/L | Standard Deviation 0.0123 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 4 h post Dose 1 | 0.011 g/L | Standard Deviation 0.00537 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 3 h post Dose 1 | 0.0095 g/L | Standard Deviation 0.00729 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | Pre-Dose 4 | 0.0128 g/L | Standard Deviation 0.00854 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 6 h post Dose 1 | 0.020 g/L | Standard Deviation 0.00678 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 8 h post Dose 4 | 0.0397 g/L | Standard Deviation 0.0157 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 8 h post Dose 1 | 0.031 g/L | Standard Deviation 0.0154 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 1 h post Dose 4 | 0.033 g/L | Standard Deviation 0.0196 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 24 h post Dose 1 | 0.0612 g/L | Standard Deviation 0.0212 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 168 h post Dose 4 | 0.0382 g/L | Standard Deviation 0.0935 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 48 h post Dose 1 | 0.0603 g/L | Standard Deviation 0.0213 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 2 h post Dose 4 | 0.0377 g/L | Standard Deviation 0.021 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | Pre-Dose 2 | 0.0507 g/L | Standard Deviation 0.0168 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 48 h post Dose 4 | 0.0562 g/L | Standard Deviation 0.00906 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C1 Inhibitor (C1INH) | 1 h post Dose 2 | 0.00833 g/L | Standard Deviation 0.00852 |
Secondary
Mean Change C4 Compliment
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
Population: Intent to Treat
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 4 h post Dose 4 | 34.8 mg/L | Standard Deviation 22.9 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | Pre-Dose 2 | 24.3 mg/L | Standard Deviation 14.5 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 120 h post Dose 4 | 16.8 mg/L | Standard Deviation 15.5 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 2 h post Dose 1 | 11.3 mg/L | Standard Deviation 13.8 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 3 h post Dose 1 | 10.2 mg/L | Standard Deviation 11.7 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 6 h post Dose 1 | 15.7 mg/L | Standard Deviation 14.2 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 8 h post Dose 1 | 16.3 mg/L | Standard Deviation 16.6 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 0 Hour (h) | 9.00 mg/L | Standard Deviation 15.4 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 1 hour (h) post Dose 1 | 11.0 mg/L | Standard Deviation 14.3 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 24 h post Dose 1 | 25.0 mg/L | Standard Deviation 15.6 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 48 h post Dose 1 | 37.4 mg/L | Standard Deviation 23.1 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 1 h post Dose 2 | 37.5 mg/L | Standard Deviation 21.6 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 120 h post Dose 1 | 35.6 mg/L | Standard Deviation 22.6 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 168 h post Dose 4 | 19.0 mg/L | Standard Deviation 18.4 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | Pre-Dose 3 | 29.0 mg/L | Standard Deviation 19.1 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 1 h post Dose 3 | 32.5 mg/L | Standard Deviation 18.7 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | Pre-Dose 4 | 32.0 mg/L | Standard Deviation 18.4 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 1 h post Dose 4 | 30.2 mg/L | Standard Deviation 18.8 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 2 h post Dose 4 | 33.3 mg/L | Standard Deviation 24.5 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 3 h post Dose 4 | 34.3 mg/L | Standard Deviation 17.9 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 4 h post Dose 1 | 11.5 mg/L | Standard Deviation 13.6 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 6 h post Dose 4 | 36.3 mg/L | Standard Deviation 21.6 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 8 h post Dose 4 | 33.6 mg/L | Standard Deviation 20.3 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 24 h post Dose 4 | 37.8 mg/L | Standard Deviation 23 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 48 h post Dose 4 | 33.0 mg/L | Standard Deviation 22.4 |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Mean Change C4 Compliment | 72 h post Dose 4 | 23.3 mg/L | Standard Deviation 20.6 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 24 h post Dose 4 | 64.7 mg/L | Standard Deviation 52.4 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 4 h post Dose 1 | 13.2 mg/L | Standard Deviation 16.8 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 48 h post Dose 1 | 49.8 mg/L | Standard Deviation 24.3 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 120 h post Dose 1 | 70.8 mg/L | Standard Deviation 28.4 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | Pre-Dose 2 | 53.3 mg/L | Standard Deviation 23.2 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | Pre-Dose 4 | 62.5 mg/L | Standard Deviation 54.2 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 72 h post Dose 4 | 72.2 mg/L | Standard Deviation 57.5 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 4 h post Dose 4 | 63.3 mg/L | Standard Deviation 56.5 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | Pre-Dose 3 | 66.3 mg/L | Standard Deviation 47 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 2 h post Dose 1 | 11.0 mg/L | Standard Deviation 18.7 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 120 h post Dose 4 | 58.7 mg/L | Standard Deviation 46.4 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 3 h post Dose 1 | 11.5 mg/L | Standard Deviation 17.6 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 1 h post Dose 3 | 69.3 mg/L | Standard Deviation 50.5 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 6 h post Dose 1 | 14.0 mg/L | Standard Deviation 18.1 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 6 h post Dose 4 | 59.7 mg/L | Standard Deviation 46.4 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 48 h post Dose 4 | 65.7 mg/L | Standard Deviation 47 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 0 Hour (h) | 13.3 mg/L | Standard Deviation 14.4 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 1 h post Dose 4 | 57.3 mg/L | Standard Deviation 53.7 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 1 hour (h) post Dose 1 | 10.3 mg/L | Standard Deviation 21.4 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 8 h post Dose 1 | 22.5 mg/L | Standard Deviation 29.1 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 8 h post Dose 4 | 56.5 mg/L | Standard Deviation 48.4 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 24 h post Dose 1 | 30.5 mg/L | Standard Deviation 19.5 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 2 h post Dose 4 | 59.7 mg/L | Standard Deviation 52.5 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 168 h post Dose 4 | 44.8 mg/L | Standard Deviation 46 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 1 h post Dose 2 | 53.2 mg/L | Standard Deviation 22.6 |
| SC CINRYZE With rHuPH20 Dose Level 2 | Mean Change C4 Compliment | 3 h post Dose 4 | 53.3 mg/L | Standard Deviation 46.2 |
Secondary
Number of Subjects With C1 INH Antibodies
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)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Number of Subjects With C1 INH Antibodies | Day 1 (pre-dose) | 0 Participants |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Number of Subjects With C1 INH Antibodies | Day 18 (168 h post Dose 4) | 0 Participants |
| Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1 | Number of Subjects With C1 INH Antibodies | 30 (±2) days after the last dose of study drug (Dose 4) | 0 Participants |
| SC CINRYZE With rHuPH20 Dose Level 2 | Number of Subjects With C1 INH Antibodies | Day 1 (pre-dose) | 0 Participants |
| SC CINRYZE With rHuPH20 Dose Level 2 | Number of Subjects With C1 INH Antibodies | Day 18 (168 h post Dose 4) | 0 Participants |
| SC CINRYZE With rHuPH20 Dose Level 2 | Number of Subjects With C1 INH Antibodies | 30 (±2) days after the last dose of study drug (Dose 4) | 0 Participants |