Trial Outcomes & Findings for A Study to Evaluate the Safety and Pharmacology of Subcutaneous Administration of CINRYZE With Recombinant Human Hyaluronidase (NCT NCT01426763)
NCT ID: NCT01426763
Last Updated: 2021-07-19
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
12 participants
Primary outcome timeframe
18 days
Results posted on
2021-07-19
Participant Flow
Participant milestones
| Measure |
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
|
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
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
|
Overall Study
COMPLETED
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Evaluate the Safety and Pharmacology of Subcutaneous Administration of CINRYZE With Recombinant Human Hyaluronidase
Baseline characteristics by cohort
| Measure |
Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1
n=6 Participants
SC injection of 1000 Units of CINRYZE with \~20,000 Units of rHuPH20 twice weekly for two weeks
|
SC CINRYZE With rHuPH20 Dose Level 2
n=6 Participants
SC injection of 2000 Units of CINRYZE with \~40,000 Units of rHuPH20 twice weekly for two weeks
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
31.5 years
STANDARD_DEVIATION 7.79 • n=93 Participants
|
33.7 years
STANDARD_DEVIATION 10.27 • n=4 Participants
|
32.6 years
STANDARD_DEVIATION 8.76 • n=27 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 18 daysOutcome measures
| Measure |
Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1
n=6 Participants
SC injection of 1000 Units of CINRYZE with \~20,000 Units of rHuPH20 twice weekly for two weeks
|
SC CINRYZE With rHuPH20 Dose Level 2
n=6 Participants
SC injection of 2000 Units of CINRYZE with \~40,000 Units of rHuPH20 twice weekly for two weeks
|
|---|---|---|
|
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
|
5 participants
|
|
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
|
5 participants
|
|
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
|
0 participants
|
|
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
|
0 participants
|
SECONDARY outcome
Timeframe: 18 daysPopulation: Intent to Treat
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 |
Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1
n=6 Participants
SC injection of 1000 Units of CINRYZE with \~20,000 Units of rHuPH20 twice weekly for two weeks
|
SC CINRYZE With rHuPH20 Dose Level 2
n=6 Participants
SC injection of 2000 Units of CINRYZE with \~40,000 Units of rHuPH20 twice weekly for two weeks
|
|---|---|---|
|
Mean Change C1 Inhibitor (C1INH)
3 h post Dose 4
|
0.0238 g/L
Standard Deviation 0.012
|
0.0333 g/L
Standard Deviation 0.0163
|
|
Mean Change C1 Inhibitor (C1INH)
4 h post Dose 4
|
0.0257 g/L
Standard Deviation 0.0142
|
0.037 g/L
Standard Deviation 0.0215
|
|
Mean Change C1 Inhibitor (C1INH)
6 h post Dose 4
|
0.0298 g/L
Standard Deviation 0.0124
|
0.039 g/L
Standard Deviation 0.025
|
|
Mean Change C1 Inhibitor (C1INH)
8 h post Dose 4
|
0.0354 g/L
Standard Deviation 0.0118
|
0.0397 g/L
Standard Deviation 0.0157
|
|
Mean Change C1 Inhibitor (C1INH)
24 h post Dose 4
|
0.0347 g/L
Standard Deviation 0.018
|
0.0623 g/L
Standard Deviation 0.0207
|
|
Mean Change C1 Inhibitor (C1INH)
48 h post Dose 4
|
0.0273 g/L
Standard Deviation 0.0171
|
0.0562 g/L
Standard Deviation 0.00906
|
|
Mean Change C1 Inhibitor (C1INH)
72 h post Dose 4
|
0.0167 g/L
Standard Deviation 0.0185
|
0.046 g/L
Standard Deviation 0.0106
|
|
Mean Change C1 Inhibitor (C1INH)
120 h post Dose 4
|
0.0165 g/L
Standard Deviation 0.0214
|
0.0157 g/L
Standard Deviation 0.00797
|
|
Mean Change C1 Inhibitor (C1INH)
168 h post Dose 4
|
0.00933 g/L
Standard Deviation 0.0201
|
0.0382 g/L
Standard Deviation 0.0935
|
|
Mean Change C1 Inhibitor (C1INH)
0 Hour (h)
|
0.0248 g/L
Standard Deviation 0.0565
|
0.00483 g/L
Standard Deviation 0.00904
|
|
Mean Change C1 Inhibitor (C1INH)
1 hour (h) post Dose 1
|
0.0273 g/L
Standard Deviation 0.065
|
0.00383 g/L
Standard Deviation 0.00417
|
|
Mean Change C1 Inhibitor (C1INH)
2 h post Dose 1
|
0.0302 g/L
Standard Deviation 0.0637
|
0.008 g/L
Standard Deviation 0.0123
|
|
Mean Change C1 Inhibitor (C1INH)
3 h post Dose 1
|
0.0275 g/L
Standard Deviation 0.0602
|
0.0095 g/L
Standard Deviation 0.00729
|
|
Mean Change C1 Inhibitor (C1INH)
4 h post Dose 1
|
0.0382 g/L
Standard Deviation 0.0652
|
0.011 g/L
Standard Deviation 0.00537
|
|
Mean Change C1 Inhibitor (C1INH)
6 h post Dose 1
|
0.0398 g/L
Standard Deviation 0.0599
|
0.020 g/L
Standard Deviation 0.00678
|
|
Mean Change C1 Inhibitor (C1INH)
8 h post Dose 1
|
0.0455 g/L
Standard Deviation 0.0624
|
0.031 g/L
Standard Deviation 0.0154
|
|
Mean Change C1 Inhibitor (C1INH)
24 h post Dose 1
|
0.0625 g/L
Standard Deviation 0.0728
|
0.0612 g/L
Standard Deviation 0.0212
|
|
Mean Change C1 Inhibitor (C1INH)
48 h post Dose 1
|
0.0665 g/L
Standard Deviation 0.0749
|
0.0603 g/L
Standard Deviation 0.0213
|
|
Mean Change C1 Inhibitor (C1INH)
Pre-Dose 2
|
0.0243 g/L
Standard Deviation 0.0234
|
0.0507 g/L
Standard Deviation 0.0168
|
|
Mean Change C1 Inhibitor (C1INH)
1 h post Dose 2
|
0.0387 g/L
Standard Deviation 0.0749
|
0.00833 g/L
Standard Deviation 0.00852
|
|
Mean Change C1 Inhibitor (C1INH)
120 h post Dose 1
|
0.020 g/L
Standard Deviation 0.00883
|
0.0388 g/L
Standard Deviation 0.0132
|
|
Mean Change C1 Inhibitor (C1INH)
Pre-Dose 3
|
0.0288 g/L
Standard Deviation 0.0644
|
0.00833 g/L
Standard Deviation 0.0095
|
|
Mean Change C1 Inhibitor (C1INH)
1 h post Dose 3
|
0.00217 g/L
Standard Deviation 0.00271
|
0.004 g/L
Standard Deviation 0.00405
|
|
Mean Change C1 Inhibitor (C1INH)
Pre-Dose 4
|
0.006 g/L
Standard Deviation 0.0119
|
0.0128 g/L
Standard Deviation 0.00854
|
|
Mean Change C1 Inhibitor (C1INH)
1 h post Dose 4
|
0.0193 g/L
Standard Deviation 0.012
|
0.033 g/L
Standard Deviation 0.0196
|
|
Mean Change C1 Inhibitor (C1INH)
2 h post Dose 4
|
0.0233 g/L
Standard Deviation 0.0126
|
0.0377 g/L
Standard Deviation 0.021
|
SECONDARY outcome
Timeframe: 18 daysPopulation: Intent to Treat
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 |
Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1
n=6 Participants
SC injection of 1000 Units of CINRYZE with \~20,000 Units of rHuPH20 twice weekly for two weeks
|
SC CINRYZE With rHuPH20 Dose Level 2
n=6 Participants
SC injection of 2000 Units of CINRYZE with \~40,000 Units of rHuPH20 twice weekly for two weeks
|
|---|---|---|
|
Mean Change C4 Compliment
1 hour (h) post Dose 1
|
11.0 mg/L
Standard Deviation 14.3
|
10.3 mg/L
Standard Deviation 21.4
|
|
Mean Change C4 Compliment
2 h post Dose 1
|
11.3 mg/L
Standard Deviation 13.8
|
11.0 mg/L
Standard Deviation 18.7
|
|
Mean Change C4 Compliment
3 h post Dose 1
|
10.2 mg/L
Standard Deviation 11.7
|
11.5 mg/L
Standard Deviation 17.6
|
|
Mean Change C4 Compliment
0 Hour (h)
|
9.00 mg/L
Standard Deviation 15.4
|
13.3 mg/L
Standard Deviation 14.4
|
|
Mean Change C4 Compliment
4 h post Dose 1
|
11.5 mg/L
Standard Deviation 13.6
|
13.2 mg/L
Standard Deviation 16.8
|
|
Mean Change C4 Compliment
6 h post Dose 1
|
15.7 mg/L
Standard Deviation 14.2
|
14.0 mg/L
Standard Deviation 18.1
|
|
Mean Change C4 Compliment
8 h post Dose 1
|
16.3 mg/L
Standard Deviation 16.6
|
22.5 mg/L
Standard Deviation 29.1
|
|
Mean Change C4 Compliment
24 h post Dose 1
|
25.0 mg/L
Standard Deviation 15.6
|
30.5 mg/L
Standard Deviation 19.5
|
|
Mean Change C4 Compliment
48 h post Dose 1
|
37.4 mg/L
Standard Deviation 23.1
|
49.8 mg/L
Standard Deviation 24.3
|
|
Mean Change C4 Compliment
Pre-Dose 2
|
24.3 mg/L
Standard Deviation 14.5
|
53.3 mg/L
Standard Deviation 23.2
|
|
Mean Change C4 Compliment
1 h post Dose 2
|
37.5 mg/L
Standard Deviation 21.6
|
53.2 mg/L
Standard Deviation 22.6
|
|
Mean Change C4 Compliment
120 h post Dose 1
|
35.6 mg/L
Standard Deviation 22.6
|
70.8 mg/L
Standard Deviation 28.4
|
|
Mean Change C4 Compliment
Pre-Dose 3
|
29.0 mg/L
Standard Deviation 19.1
|
66.3 mg/L
Standard Deviation 47.0
|
|
Mean Change C4 Compliment
1 h post Dose 3
|
32.5 mg/L
Standard Deviation 18.7
|
69.3 mg/L
Standard Deviation 50.5
|
|
Mean Change C4 Compliment
Pre-Dose 4
|
32.0 mg/L
Standard Deviation 18.4
|
62.5 mg/L
Standard Deviation 54.2
|
|
Mean Change C4 Compliment
1 h post Dose 4
|
30.2 mg/L
Standard Deviation 18.8
|
57.3 mg/L
Standard Deviation 53.7
|
|
Mean Change C4 Compliment
2 h post Dose 4
|
33.3 mg/L
Standard Deviation 24.5
|
59.7 mg/L
Standard Deviation 52.5
|
|
Mean Change C4 Compliment
3 h post Dose 4
|
34.3 mg/L
Standard Deviation 17.9
|
53.3 mg/L
Standard Deviation 46.2
|
|
Mean Change C4 Compliment
4 h post Dose 4
|
34.8 mg/L
Standard Deviation 22.9
|
63.3 mg/L
Standard Deviation 56.5
|
|
Mean Change C4 Compliment
6 h post Dose 4
|
36.3 mg/L
Standard Deviation 21.6
|
59.7 mg/L
Standard Deviation 46.4
|
|
Mean Change C4 Compliment
8 h post Dose 4
|
33.6 mg/L
Standard Deviation 20.3
|
56.5 mg/L
Standard Deviation 48.4
|
|
Mean Change C4 Compliment
24 h post Dose 4
|
37.8 mg/L
Standard Deviation 23.0
|
64.7 mg/L
Standard Deviation 52.4
|
|
Mean Change C4 Compliment
48 h post Dose 4
|
33.0 mg/L
Standard Deviation 22.4
|
65.7 mg/L
Standard Deviation 47.0
|
|
Mean Change C4 Compliment
72 h post Dose 4
|
23.3 mg/L
Standard Deviation 20.6
|
72.2 mg/L
Standard Deviation 57.5
|
|
Mean Change C4 Compliment
120 h post Dose 4
|
16.8 mg/L
Standard Deviation 15.5
|
58.7 mg/L
Standard Deviation 46.4
|
|
Mean Change C4 Compliment
168 h post Dose 4
|
19.0 mg/L
Standard Deviation 18.4
|
44.8 mg/L
Standard Deviation 46.0
|
SECONDARY outcome
Timeframe: 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 measures
| Measure |
Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1
n=6 Participants
SC injection of 1000 Units of CINRYZE with \~20,000 Units of rHuPH20 twice weekly for two weeks
|
SC CINRYZE With rHuPH20 Dose Level 2
n=6 Participants
SC injection of 2000 Units of CINRYZE with \~40,000 Units of rHuPH20 twice weekly for two weeks
|
|---|---|---|
|
Number of Subjects With C1 INH Antibodies
Day 1 (pre-dose)
|
0 Participants
|
0 Participants
|
|
Number of Subjects With C1 INH Antibodies
Day 18 (168 h post Dose 4)
|
0 Participants
|
0 Participants
|
|
Number of Subjects With C1 INH Antibodies
30 (±2) days after the last dose of study drug (Dose 4)
|
0 Participants
|
0 Participants
|
Adverse Events
Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
SC CINRYZE With rHuPH20 Dose Level 2
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Subcutaneous (SC) CINRYZE With Recombinant Human Hyaluronidase ph20 (rHuPH20) Dose Level 1
n=6 participants at risk
SC injection of 1000 Units of CINRYZE with \~20,000 Units of rHuPH20 twice weekly for two weeks
|
SC CINRYZE With rHuPH20 Dose Level 2
n=6 participants at risk
SC injection of 2000 Units of CINRYZE with \~40,000 Units of rHuPH20 twice weekly for two weeks
|
|---|---|---|
|
General disorders
Injection site erythema
|
83.3%
5/6
|
83.3%
5/6
|
|
General disorders
Injection site hemorrhage
|
16.7%
1/6
|
0.00%
0/6
|
|
General disorders
Injection site induration
|
0.00%
0/6
|
16.7%
1/6
|
|
General disorders
Injection site edema
|
16.7%
1/6
|
0.00%
0/6
|
|
General disorders
Injection site pain
|
66.7%
4/6
|
16.7%
1/6
|
|
General disorders
Injection site pruritus
|
16.7%
1/6
|
0.00%
0/6
|
|
General disorders
Injection site swelling
|
33.3%
2/6
|
0.00%
0/6
|
|
Infections and infestations
Upper respiratory tract infection
|
16.7%
1/6
|
0.00%
0/6
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/6
|
16.7%
1/6
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/6
|
16.7%
1/6
|
|
Nervous system disorders
Headache
|
0.00%
0/6
|
16.7%
1/6
|
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