Trial Outcomes & Findings for A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous CINRYZE Administration (NCT NCT01095497)
NCT ID: NCT01095497
Last Updated: 2021-07-09
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
26 participants
Primary outcome timeframe
18 days in each treatment period
Results posted on
2021-07-09
Participant Flow
Participant milestones
| Measure |
IV CINRYZE First, Then SC CINRYZE Dose 1
Subjects participated in two 18-day treatment periods, separated by a washout period of at least 14 days. In Period 1, subjects received 1000 Units of intravenous (IV) CINRYZE twice weekly for two weeks. In Period 2, subjects received 1000 Units of subcutaneous (SC) CINRYZE twice weekly for two weeks.
|
IV CINRYZE First, Then SC CINRYZE Dose 2
Subjects participated in two 18-day treatment periods, separated by a washout period of at least 14 days. In Period 1, subjects received 1000 Units of IV CINRYZE twice weekly for two weeks. In Period 2, subjects received 2000 Units of SC CINRYZE twice weekly for two weeks.
|
|---|---|---|
|
Intravenous CINRYZE
STARTED
|
14
|
12
|
|
Intravenous CINRYZE
COMPLETED
|
13
|
12
|
|
Intravenous CINRYZE
NOT COMPLETED
|
1
|
0
|
|
Subcutaneous CINRYZE
STARTED
|
13
|
12
|
|
Subcutaneous CINRYZE
COMPLETED
|
12
|
12
|
|
Subcutaneous CINRYZE
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous CINRYZE Administration
Baseline characteristics by cohort
| Measure |
IV CINRYZE First, Then SC CINRYZE Dose 1
n=14 Participants
Subjects participated in two 18-day treatment periods, separated by a washout period of at least 14 days. In Period 1, subjects received 1000 Units of IV CINRYZE twice weekly for two weeks. In Period 2, subjects received 1000 Units of SC CINRYZE twice weekly for two weeks.
|
IV CINRYZE First, Then SC CINRYZE Dose 2
n=12 Participants
Subjects participated in two 18-day treatment periods, separated by a washout period of at least 14 days. In Period 1, subjects received 1000 Units of IV CINRYZE twice weekly for two weeks. In Period 2, subjects received 2000 Units of SC CINRYZE twice weekly for two weeks.
|
Total
n=26 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
28.6 years
STANDARD_DEVIATION 12.70 • n=5 Participants
|
37.3 years
STANDARD_DEVIATION 15.92 • n=7 Participants
|
32.7 years
STANDARD_DEVIATION 14.66 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 18 days in each treatment periodPopulation: Safety Analysis Set
Outcome measures
| Measure |
Intravenous (IV) CINRYZE
n=26 Participants
1000 Units of IV CINRYZE twice weekly for two weeks
|
Subcutaneous (SC) CINRYZE Dose 1
n=13 Participants
1000 Units of SC CINRYZE twice weekly for two weeks
|
SC CINRYZE Dose 2
n=12 Participants
2000 Units of SC CINRYZE twice weekly for two weeks
|
|---|---|---|---|
|
Incidence and Severity of Adverse Events, Number of Subjects With Local Injection Site Reactions, and Number of Subjects Who Discontinue Study Drug or Withdraw From the Study.
Number of subjects with adverse events
|
12 Participants
0.019
|
10 Participants
0.027
|
11 Participants
0.010
|
|
Incidence and Severity of Adverse Events, Number of Subjects With Local Injection Site Reactions, and Number of Subjects Who Discontinue Study Drug or Withdraw From the Study.
Number of subjects with injection site reactions
|
1 Participants
0.033
|
10 Participants
0.032
|
11 Participants
0.010
|
|
Incidence and Severity of Adverse Events, Number of Subjects With Local Injection Site Reactions, and Number of Subjects Who Discontinue Study Drug or Withdraw From the Study.
Number of subjects who discontinued study drug
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Incidence and Severity of Adverse Events, Number of Subjects With Local Injection Site Reactions, and Number of Subjects Who Discontinue Study Drug or Withdraw From the Study.
Number of subjects who withdrew from the study
|
1 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 18 days in each treatment periodPopulation: Intent to Treat Population
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.
Outcome measures
| Measure |
Intravenous (IV) CINRYZE
n=25 Participants
1000 Units of IV CINRYZE twice weekly for two weeks
|
Subcutaneous (SC) CINRYZE Dose 1
n=13 Participants
1000 Units of SC CINRYZE twice weekly for two weeks
|
SC CINRYZE Dose 2
n=12 Participants
2000 Units of SC CINRYZE twice weekly for two weeks
|
|---|---|---|---|
|
Mean Change C1 Inhibitor (C1INH)
1 hour (h) post Dose 1
|
0.075 g/L
Standard Deviation 0.023
|
-0.002 g/L
Standard Deviation 0.008
|
-0.001 g/L
Standard Deviation 0.006
|
|
Mean Change C1 Inhibitor (C1INH)
3 h post Dose 1
|
0.070 g/L
Standard Deviation 0.023
|
-0.002 g/L
Standard Deviation 0.007
|
-0.002 g/L
Standard Deviation 0.007
|
|
Mean Change C1 Inhibitor (C1INH)
4 h post Dose 1
|
0.065 g/L
Standard Deviation 0.022
|
0.003 g/L
Standard Deviation 0.005
|
0.003 g/L
Standard Deviation 0.007
|
|
Mean Change C1 Inhibitor (C1INH)
8 h post Dose 1
|
0.062 g/L
Standard Deviation 0.019
|
0.003 g/L
Standard Deviation 0.010
|
0.009 g/L
Standard Deviation 0.008
|
|
Mean Change C1 Inhibitor (C1INH)
24 h post Dose 1
|
0.049 g/L
Standard Deviation 0.016
|
0.016 g/L
Standard Deviation 0.023
|
0.021 g/L
Standard Deviation 0.011
|
|
Mean Change C1 Inhibitor (C1INH)
48 h post Dose 1
|
0.035 g/L
Standard Deviation 0.017
|
0.019 g/L
Standard Deviation 0.030
|
0.028 g/L
Standard Deviation 0.009
|
|
Mean Change C1 Inhibitor (C1INH)
Pre-Dose 2
|
0.027 g/L
Standard Deviation 0.024
|
0.011 g/L
Standard Deviation 0.021
|
0.026 g/L
Standard Deviation 0.008
|
|
Mean Change C1 Inhibitor (C1INH)
1 h post Dose 2
|
0.088 g/L
Standard Deviation 0.036
|
0.013 g/L
Standard Deviation 0.022
|
0.027 g/L
Standard Deviation 0.009
|
|
Mean Change C1 Inhibitor (C1INH)
120 h post Dose 1
|
0.042 g/L
Standard Deviation 0.018
|
0.024 g/L
Standard Deviation 0.032
|
0.037 g/L
Standard Deviation 0.009
|
|
Mean Change C1 Inhibitor (C1INH)
Pre-Dose 3
|
0.019 g/L
Standard Deviation 0.016
|
0.012 g/L
Standard Deviation 0.024
|
0.024 g/L
Standard Deviation 0.009
|
|
Mean Change C1 Inhibitor (C1INH)
1 h post Dose 3
|
0.093 g/L
Standard Deviation 0.028
|
0.012 g/L
Standard Deviation 0.024
|
0.024 g/L
Standard Deviation 0.010
|
|
Mean Change C1 Inhibitor (C1INH)
Pre-Dose 4
|
0.024 g/L
Standard Deviation 0.020
|
0.019 g/L
Standard Deviation 0.034
|
0.030 g/L
Standard Deviation 0.015
|
|
Mean Change C1 Inhibitor (C1INH)
1 h post Dose 4
|
0.098 g/L
Standard Deviation 0.035
|
0.010 g/L
Standard Deviation 0.031
|
0.031 g/L
Standard Deviation 0.012
|
|
Mean Change C1 Inhibitor (C1INH)
2 h post Dose 4
|
0.092 g/L
Standard Deviation 0.032
|
0.012 g/L
Standard Deviation 0.028
|
0.029 g/L
Standard Deviation 0.015
|
|
Mean Change C1 Inhibitor (C1INH)
3 h post Dose 4
|
0.087 g/L
Standard Deviation 0.031
|
0.014 g/L
Standard Deviation 0.030
|
0.031 g/L
Standard Deviation 0.014
|
|
Mean Change C1 Inhibitor (C1INH)
4 h post Dose 4
|
0.086 g/L
Standard Deviation 0.031
|
0.016 g/L
Standard Deviation 0.029
|
0.035 g/L
Standard Deviation 0.015
|
|
Mean Change C1 Inhibitor (C1INH)
6 h post Dose 4
|
0.081 g/L
Standard Deviation 0.031
|
0.016 g/L
Standard Deviation 0.028
|
0.034 g/L
Standard Deviation 0.015
|
|
Mean Change C1 Inhibitor (C1INH)
24 h post Dose 4
|
0.060 g/L
Standard Deviation 0.025
|
0.026 g/L
Standard Deviation 0.032
|
0.043 g/L
Standard Deviation 0.009
|
|
Mean Change C1 Inhibitor (C1INH)
72 h post Dose 4
|
0.025 g/L
Standard Deviation 0.022
|
0.017 g/L
Standard Deviation 0.026
|
0.037 g/L
Standard Deviation 0.013
|
|
Mean Change C1 Inhibitor (C1INH)
120 h post Dose 4
|
0.008 g/L
Standard Deviation 0.018
|
0.003 g/L
Standard Deviation 0.022
|
0.025 g/L
Standard Deviation 0.012
|
|
Mean Change C1 Inhibitor (C1INH)
2 h post Dose 1
|
0.070 g/L
Standard Deviation 0.021
|
-0.002 g/L
Standard Deviation 0.008
|
-0.001 g/L
Standard Deviation 0.004
|
|
Mean Change C1 Inhibitor (C1INH)
6 h post Dose 1
|
0.064 g/L
Standard Deviation 0.018
|
0.002 g/L
Standard Deviation 0.009
|
0.006 g/L
Standard Deviation 0.007
|
|
Mean Change C1 Inhibitor (C1INH)
8 h post Dose 4
|
0.080 g/L
Standard Deviation 0.029
|
0.017 g/L
Standard Deviation 0.032
|
0.036 g/L
Standard Deviation 0.012
|
|
Mean Change C1 Inhibitor (C1INH)
48 h post Dose 4
|
0.038 g/L
Standard Deviation 0.022
|
0.022 g/L
Standard Deviation 0.028
|
0.045 g/L
Standard Deviation 0.012
|
|
Mean Change C1 Inhibitor (C1INH)
168 h post Dose 4
|
0.005 g/L
Standard Deviation 0.016
|
0.005 g/L
Standard Deviation 0.024
|
0.017 g/L
Standard Deviation 0.011
|
SECONDARY outcome
Timeframe: 18 days in each treatment periodPopulation: Intent to Treat Population
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.
Outcome measures
| Measure |
Intravenous (IV) CINRYZE
n=25 Participants
1000 Units of IV CINRYZE twice weekly for two weeks
|
Subcutaneous (SC) CINRYZE Dose 1
n=13 Participants
1000 Units of SC CINRYZE twice weekly for two weeks
|
SC CINRYZE Dose 2
n=12 Participants
2000 Units of SC CINRYZE twice weekly for two weeks
|
|---|---|---|---|
|
Mean Change C4 Compliment
1 hour (h) post Dose 1
|
-7.5 mg/L
Standard Deviation 15.4
|
-12.9 mg/L
Standard Deviation 15.6
|
0.1 mg/L
Standard Deviation 8.0
|
|
Mean Change C4 Compliment
4 h post Dose 1
|
2.7 mg/L
Standard Deviation 14.8
|
-5.3 mg/L
Standard Deviation 18.5
|
8.8 mg/L
Standard Deviation 23.7
|
|
Mean Change C4 Compliment
Pre-Dose 4
|
34.4 mg/L
Standard Deviation 26.9
|
5.4 mg/L
Standard Deviation 27.6
|
50.5 mg/L
Standard Deviation 18.7
|
|
Mean Change C4 Compliment
1 h post Dose 4
|
28.6 mg/L
Standard Deviation 27.0
|
1.9 mg/L
Standard Deviation 25.0
|
51.2 mg/L
Standard Deviation 22.6
|
|
Mean Change C4 Compliment
2 h post Dose 4
|
29.4 mg/L
Standard Deviation 26.2
|
6.6 mg/L
Standard Deviation 25.2
|
49.4 mg/L
Standard Deviation 21.1
|
|
Mean Change C4 Compliment
3 h post Dose 4
|
34.7 mg/L
Standard Deviation 24.9
|
8.8 mg/L
Standard Deviation 25.0
|
54.9 mg/L
Standard Deviation 26.4
|
|
Mean Change C4 Compliment
4 h post Dose 4
|
33.7 mg/L
Standard Deviation 31.1
|
9.2 mg/L
Standard Deviation 27.0
|
62.8 mg/L
Standard Deviation 41.2
|
|
Mean Change C4 Compliment
8 h post Dose 4
|
41.9 mg/L
Standard Deviation 30.1
|
6.4 mg/L
Standard Deviation 27.8
|
67.3 mg/L
Standard Deviation 53.4
|
|
Mean Change C4 Compliment
72 h post Dose 4
|
46.1 mg/L
Standard Deviation 36.2
|
10.9 mg/L
Standard Deviation 27.9
|
62.6 mg/L
Standard Deviation 43.8
|
|
Mean Change C4 Compliment
120 h post Dose 4
|
11.0 mg/L
Standard Deviation 32.1
|
-4.5 mg/L
Standard Deviation 26.0
|
47.2 mg/L
Standard Deviation 32.3
|
|
Mean Change C4 Compliment
168 h post Dose 4
|
-0.6 mg/L
Standard Deviation 27.1
|
2.2 mg/L
Standard Deviation 24.5
|
36.5 mg/L
Standard Deviation 32.9
|
|
Mean Change C4 Compliment
2 h post Dose 1
|
-0.6 mg/L
Standard Deviation 10.2
|
-3.8 mg/L
Standard Deviation 18.2
|
-3.3 mg/L
Standard Deviation 8.9
|
|
Mean Change C4 Compliment
3 h post Dose 1
|
-1.3 mg/L
Standard Deviation 13.5
|
-0.6 mg/L
Standard Deviation 10.9
|
2.5 mg/L
Standard Deviation 11.1
|
|
Mean Change C4 Compliment
6 h post Dose 1
|
12.0 mg/L
Standard Deviation 24.8
|
-0.6 mg/L
Standard Deviation 37.1
|
8.1 mg/L
Standard Deviation 21.0
|
|
Mean Change C4 Compliment
8 h post Dose 1
|
13.0 mg/L
Standard Deviation 20.7
|
-8.2 mg/L
Standard Deviation 24.6
|
11.2 mg/L
Standard Deviation 27.4
|
|
Mean Change C4 Compliment
24 h post Dose 1
|
25.5 mg/L
Standard Deviation 30.3
|
2.9 mg/L
Standard Deviation 25.4
|
14.3 mg/L
Standard Deviation 12.7
|
|
Mean Change C4 Compliment
48 h post Dose 1
|
31.0 mg/L
Standard Deviation 25.3
|
6.2 mg/L
Standard Deviation 23.1
|
23.3 mg/L
Standard Deviation 18.0
|
|
Mean Change C4 Compliment
Pre-Dose 2
|
29.5 mg/L
Standard Deviation 23.9
|
8.7 mg/L
Standard Deviation 23.4
|
30.2 mg/L
Standard Deviation 15.3
|
|
Mean Change C4 Compliment
1 h post Dose 2
|
24.7 mg/L
Standard Deviation 26.4
|
5.6 mg/L
Standard Deviation 23.7
|
31.8 mg/L
Standard Deviation 19.3
|
|
Mean Change C4 Compliment
120 h post Dose 1
|
53.1 mg/L
Standard Deviation 24.4
|
21.7 mg/L
Standard Deviation 22.7
|
37.9 mg/L
Standard Deviation 28.1
|
|
Mean Change C4 Compliment
Pre-Dose 3
|
28.1 mg/L
Standard Deviation 29.3
|
7.3 mg/L
Standard Deviation 20.6
|
57.3 mg/L
Standard Deviation 46.6
|
|
Mean Change C4 Compliment
1 h post Dose 3
|
26.0 mg/L
Standard Deviation 20.9
|
5.8 mg/L
Standard Deviation 22.3
|
40.4 mg/L
Standard Deviation 26.5
|
|
Mean Change C4 Compliment
6 h post Dose 4
|
39.4 mg/L
Standard Deviation 26.8
|
4.2 mg/L
Standard Deviation 26.5
|
67.1 mg/L
Standard Deviation 57.3
|
|
Mean Change C4 Compliment
24 h post Dose 4
|
56.5 mg/L
Standard Deviation 36.0
|
4.0 mg/L
Standard Deviation 23.8
|
49.3 mg/L
Standard Deviation 31.6
|
|
Mean Change C4 Compliment
48 h post Dose 4
|
54.9 mg/L
Standard Deviation 34.6
|
8.2 mg/L
Standard Deviation 23.6
|
56.5 mg/L
Standard Deviation 29.2
|
SECONDARY outcome
Timeframe: 18 days in each treatment periodOutcome measures
| Measure |
Intravenous (IV) CINRYZE
n=26 Participants
1000 Units of IV CINRYZE twice weekly for two weeks
|
Subcutaneous (SC) CINRYZE Dose 1
n=13 Participants
1000 Units of SC CINRYZE twice weekly for two weeks
|
SC CINRYZE Dose 2
n=12 Participants
2000 Units of SC CINRYZE twice weekly for two weeks
|
|---|---|---|---|
|
Number of Participants With C1 Inhibitor (INH) Antibodies
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Intravenous (IV) CINRYZE
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Subcutaneous (SC) CINRYZE Dose 1
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
SC CINRYZE Dose 2
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Intravenous (IV) CINRYZE
n=26 participants at risk
1000 Units of IV CYNRYZE twice weekly for two weeks
|
Subcutaneous (SC) CINRYZE Dose 1
n=13 participants at risk
1000 Units of SC CINRYZE twice weekly for two weeks
|
SC CINRYZE Dose 2
n=12 participants at risk
2000 Units of SC CINRYZE twice weekly for two weeks
|
|---|---|---|---|
|
General disorders
Injection site pain
|
0.00%
0/26
|
76.9%
10/13
|
66.7%
8/12
|
|
Congenital, familial and genetic disorders
Hereditary angioedema
|
19.2%
5/26
|
15.4%
2/13
|
0.00%
0/12
|
|
General disorders
Injection site erythema
|
0.00%
0/26
|
30.8%
4/13
|
16.7%
2/12
|
|
Nervous system disorders
Headache
|
3.8%
1/26
|
7.7%
1/13
|
16.7%
2/12
|
|
General disorders
Injection site hematoma
|
0.00%
0/26
|
7.7%
1/13
|
16.7%
2/12
|
|
General disorders
Injection site pruritus
|
0.00%
0/26
|
15.4%
2/13
|
8.3%
1/12
|
|
Skin and subcutaneous tissue disorders
Acne cystic
|
3.8%
1/26
|
0.00%
0/13
|
8.3%
1/12
|
|
Gastrointestinal disorders
Diarrhea
|
3.8%
1/26
|
7.7%
1/13
|
0.00%
0/12
|
|
General disorders
Injection site swelling
|
0.00%
0/26
|
7.7%
1/13
|
8.3%
1/12
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER