Trial Outcomes & Findings for Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks in Patients With Hereditary Angioedema (NCT NCT00262301)
NCT ID: NCT00262301
Last Updated: 2012-10-02
Results Overview
The time to beginning of relief of symptoms has been assessed by using a patient-reported visual analogue scale ("VAS") ranging from 0 mm (no symptoms at all) to 100 mm (extremely disabling). Time to beginning of relief of symptoms at the location that showed first "VAS" score decrease of at least 20 mm from baseline score (t= 0 min) to the next assessment time-point). Assessment time-points were taken on pre-scheduled time-points after drug administration: baseline (0 minutes), 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 48 hours. Time to beginning of relief has been calculated as median time, by using the exact time-points on which each assessment was performed.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
75 participants
Primary outcome timeframe
up to 48 hours after study drug administration
Results posted on
2012-10-02
Participant Flow
During the double-blind phase of the study, patients were randomized once to receive 100 IU/kg "rhC1INH" or Saline in a ratio of 1:1. After conclusion of the double-blind phase, patients with subsequent eligible attacks could be treated with open-label 1 vial (2100 IU) of "rhC1INH".
Patients could be enrolled into the open-label phase of the study after conclusion of the double-blind phase.
Participant milestones
| Measure |
100 IU/kg "rhC1INH"
Includes all subjects randomized and who received 100 IU/kg recombinant human C1 inhibitor in the double-blind phase.
|
Saline
Includes all subjects randomized and who received Saline solution in the double-blind phase.
|
1 Vial (2100 IU) "rhC1INH"
Includes all subjects who received, 1 vial (2100 IU) open-label "rhC1INH" in the open-label extension phase. Patients received 1 vial initially and could receive an additional 1-2 vials within 4 hours at the investigator's discretion.
|
|---|---|---|---|
|
Double-blind Phase
STARTED
|
16
|
16
|
0
|
|
Double-blind Phase
COMPLETED
|
15
|
15
|
0
|
|
Double-blind Phase
NOT COMPLETED
|
1
|
1
|
0
|
|
Open-label Phase
STARTED
|
0
|
0
|
57
|
|
Open-label Phase
COMPLETED
|
0
|
0
|
57
|
|
Open-label Phase
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
100 IU/kg "rhC1INH"
Includes all subjects randomized and who received 100 IU/kg recombinant human C1 inhibitor in the double-blind phase.
|
Saline
Includes all subjects randomized and who received Saline solution in the double-blind phase.
|
1 Vial (2100 IU) "rhC1INH"
Includes all subjects who received, 1 vial (2100 IU) open-label "rhC1INH" in the open-label extension phase. Patients received 1 vial initially and could receive an additional 1-2 vials within 4 hours at the investigator's discretion.
|
|---|---|---|---|
|
Double-blind Phase
Lost to Follow-up
|
1
|
0
|
0
|
|
Double-blind Phase
worsening of "HAE" symptoms
|
0
|
1
|
0
|
Baseline Characteristics
Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks in Patients With Hereditary Angioedema
Baseline characteristics by cohort
| Measure |
100 IU/kg "rhC1INH"
n=16 Participants
Includes all subjects randomized who received 100 IU/kg recombinant human C1 inhibitor in the double-blind phase.
|
Saline
n=16 Participants
Includes all subjects randomized and who received Saline solution in the double-blind phase.
|
1 Vial (2100 IU) "rhC1INH"
n=43 Participants
Includes all subjects who received 1 vial (2100 IU) open-label "rhC1INH" in the open-label extension phase.
|
Total
n=75 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
13 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
58 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
45 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: up to 48 hours after study drug administrationPopulation: The full analysis set ("FAS" or "mITT") was defined as the set of patients who provided Informed Consent, were randomized and took at least one dose of the study drug administration.
The time to beginning of relief of symptoms has been assessed by using a patient-reported visual analogue scale ("VAS") ranging from 0 mm (no symptoms at all) to 100 mm (extremely disabling). Time to beginning of relief of symptoms at the location that showed first "VAS" score decrease of at least 20 mm from baseline score (t= 0 min) to the next assessment time-point). Assessment time-points were taken on pre-scheduled time-points after drug administration: baseline (0 minutes), 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 48 hours. Time to beginning of relief has been calculated as median time, by using the exact time-points on which each assessment was performed.
Outcome measures
| Measure |
100 IU/kg "rhC1INH"
n=16 Participants
Includes all subjects randomized who received 100 IU/kg recombinant human C1 inhibitor in the double-blind phase.
|
Saline
n=16 Participants
Includes all subjects randomized and who received Saline solution in the double-blind phase.
|
1 Vial (2100 IU) "rhC1INH"
n=57 Participants
Includes all subjects who received 1 vial (2100 IU) open-label "rhC1INH" in the open-label extension phase.
|
|---|---|---|---|
|
Time to Beginning of Relief of Symptoms
|
62 minutes
Interval 15.0 to 1470.0
|
508 minutes
Interval 15.0 to 2880.0
|
61 minutes
Interval 15.0 to 1455.0
|
SECONDARY outcome
Timeframe: up to 48 hours after study drug administrationPopulation: The full analysis set ("FAS" or "mITT") was defined as the set of patients who provided Informed Consent, were randomized and took at least one dose of study drug administration.
the time to minimal symptoms was the time to minimal symptoms for an attack, assessed using the Visual Analogue Scale ("VAS") score. Symptoms were said to be minimal when the "VAS" score at all locations was below 20 mm. Assessment time-points were: baseline (0 minutes), 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 48 hours. Time to minimal symptoms has been calculated by using the exact time-points on which each assessment was performed.
Outcome measures
| Measure |
100 IU/kg "rhC1INH"
n=16 Participants
Includes all subjects randomized who received 100 IU/kg recombinant human C1 inhibitor in the double-blind phase.
|
Saline
n=16 Participants
Includes all subjects randomized and who received Saline solution in the double-blind phase.
|
1 Vial (2100 IU) "rhC1INH"
n=57 Participants
Includes all subjects who received 1 vial (2100 IU) open-label "rhC1INH" in the open-label extension phase.
|
|---|---|---|---|
|
Time to Minimal Symptoms
|
480 minutes
Interval 15.0 to 2400.0
|
1440 minutes
Interval 31.0 to 2885.0
|
241 minutes
Interval 15.0 to 4333.0
|
Adverse Events
100 IU/kg "rhC1INH"
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Saline
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
1 Vial (2100 IU) "rhC1INH"
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
100 IU/kg "rhC1INH"
n=16 participants at risk
Includes all subjects randomized who received 100 IU/kg recombinant human C1 inhibitor in the double-blind phase.
|
Saline
n=16 participants at risk
Includes all subjects randomized and who received Saline solution in the double-blind phase.
|
1 Vial (2100 IU) "rhC1INH"
n=57 participants at risk
Includes all subjects who received 1 vial (2100 IU) open-label "rhC1INH" in the open-label extension phase.
|
|---|---|---|---|
|
Investigations
Prostate examination
|
0.00%
0/16 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
6.2%
1/16 • Number of events 1 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
0.00%
0/57 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
|
Hepatobiliary disorders
Biliary colic
|
0.00%
0/16 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
6.2%
1/16 • Number of events 1 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
0.00%
0/57 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
Other adverse events
| Measure |
100 IU/kg "rhC1INH"
n=16 participants at risk
Includes all subjects randomized who received 100 IU/kg recombinant human C1 inhibitor in the double-blind phase.
|
Saline
n=16 participants at risk
Includes all subjects randomized and who received Saline solution in the double-blind phase.
|
1 Vial (2100 IU) "rhC1INH"
n=57 participants at risk
Includes all subjects who received 1 vial (2100 IU) open-label "rhC1INH" in the open-label extension phase.
|
|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
pain in extremity
|
0.00%
0/16 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
6.2%
1/16 • Number of events 1 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
0.00%
0/57 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
|
Vascular disorders
hypotension
|
0.00%
0/16 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
6.2%
1/16 • Number of events 1 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
0.00%
0/57 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
|
General disorders
pain
|
0.00%
0/16 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
12.5%
2/16 • Number of events 2 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
0.00%
0/57 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
|
Nervous system disorders
headache
|
6.2%
1/16 • Number of events 1 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
12.5%
2/16 • Number of events 2 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
5.3%
3/57 • Number of events 3 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
|
Gastrointestinal disorders
nausea
|
0.00%
0/16 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
0.00%
0/16 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
5.3%
3/57 • Number of events 3 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
|
Reproductive system and breast disorders
menstrual disorder
|
6.2%
1/16 • Number of events 1 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
0.00%
0/16 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
0.00%
0/57 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
|
Reproductive system and breast disorders
scrotal swelling
|
6.2%
1/16 • Number of events 1 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
0.00%
0/16 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
0.00%
0/57 • Treatment-Emergent-Adverse-Events ("TEAEs") were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The investigator must provide a copy of any results communication to the sponsor for review at least 30 days prior to its submission or disclosure. The sponsor may request to delete information identified by sponsor as confidential information prior to submitting such manuscript and/or abstract for publication. For a multi-center study, the investigator must wait (i) at least 24 months after the study is completed at all sites or (ii) until after the multi-center publication.
- Publication restrictions are in place
Restriction type: OTHER