Trial Outcomes & Findings for Human C1 Esterase Inhibitor (C1-INH) in Subjects With Acute Abdominal or Facial Hereditary Angioedema (HAE) Attacks (NCT NCT00168103)
NCT ID: NCT00168103
Last Updated: 2015-03-31
Results Overview
The start of symptom relief was determined by subject self-assessment. Time to start of symptom relief was set to 24 hours if the subject received rescue medication (blinded study medication, narcotic analgesics, antiemetics, open-label C1-INH, or fresh frozen plasma) at any time point after the start of study treatment but before start of relief.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
126 participants
Primary outcome timeframe
Up to 24 h after start of study treatment
Results posted on
2015-03-31
Participant Flow
This was a multinational study enrolling subjects at 36 study centers in 15 countries.
A screening visit was performed before the subject presented with an hereditary angioedema (HAE) attack at the study center. Study entry was defined to occur with administration of study treatment. One subject enrolled received study treatment without being randomized and is listed separately in the participant flow.
Participant milestones
| Measure |
C1-INH 10 U/kg bw
Includes all subjects enrolled and randomized to the C1 Esterase Inhibitor (C1-INH) 10 Units (U)/kg body weight (bw) arm.
|
C1-INH 20 U/kg bw
Includes all subjects enrolled and randomized to the C1-INH 20 U/kg bw arm.
|
Placebo
Includes all subjects enrolled and randomized to the Placebo arm.
|
Not Randomized
Includes one subject enrolled who was not randomized but received treatment with 20 U/kg bw C1-INH.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
40
|
43
|
42
|
1
|
|
Overall Study
COMPLETED
|
38
|
38
|
41
|
1
|
|
Overall Study
NOT COMPLETED
|
2
|
5
|
1
|
0
|
Reasons for withdrawal
| Measure |
C1-INH 10 U/kg bw
Includes all subjects enrolled and randomized to the C1 Esterase Inhibitor (C1-INH) 10 Units (U)/kg body weight (bw) arm.
|
C1-INH 20 U/kg bw
Includes all subjects enrolled and randomized to the C1-INH 20 U/kg bw arm.
|
Placebo
Includes all subjects enrolled and randomized to the Placebo arm.
|
Not Randomized
Includes one subject enrolled who was not randomized but received treatment with 20 U/kg bw C1-INH.
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
3
|
0
|
0
|
Baseline Characteristics
Human C1 Esterase Inhibitor (C1-INH) in Subjects With Acute Abdominal or Facial Hereditary Angioedema (HAE) Attacks
Baseline characteristics by cohort
| Measure |
C1-INH 10 U/kg bw
n=39 Participants
Baseline characteristics were calculated only for the intention to treat (ITT) and per protocol (PP) analysis populations, not for all enrolled subjects. Baseline data presented here are for subjects included in the ITT population. One (1) subject enrolled and randomized to the C1-INH 10 U/kg bw group was excluded from the ITT analysis population.
|
C1-INH 20 U/kg bw
n=43 Participants
Baseline data presented here are for subjects included in the ITT population. All subjects enrolled and randomized to the C1-INH 20 U/kg bw arm were included in the ITT analysis population.
|
Placebo
n=42 Participants
Baseline data presented here are for subjects included in the ITT population. All subjects enrolled and randomized to the Placebo arm were included in the ITT analysis population.
|
Total
n=124 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
3 to < 12 years
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
3 participants
n=4 Participants
|
|
Age, Customized
12 to < 17 years
|
3 participants
n=5 Participants
|
4 participants
n=7 Participants
|
3 participants
n=5 Participants
|
10 participants
n=4 Participants
|
|
Age, Customized
17 to < 65 years
|
35 participants
n=5 Participants
|
35 participants
n=7 Participants
|
37 participants
n=5 Participants
|
107 participants
n=4 Participants
|
|
Age, Customized
>= 65 years
|
1 participants
n=5 Participants
|
3 participants
n=7 Participants
|
0 participants
n=5 Participants
|
4 participants
n=4 Participants
|
|
Age, Continuous
|
33.1 years
STANDARD_DEVIATION 12.77 • n=5 Participants
|
34.6 years
STANDARD_DEVIATION 14.91 • n=7 Participants
|
31.5 years
STANDARD_DEVIATION 13.57 • n=5 Participants
|
33.1 years
STANDARD_DEVIATION 13.76 • n=4 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
84 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
40 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
White
|
36 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
111 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Black
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaskan Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Intensity of Baseline HAE Attack
Moderate
|
32 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
85 Participants
n=4 Participants
|
|
Intensity of Baseline HAE Attack
Severe
|
7 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
39 Participants
n=4 Participants
|
|
Primary Disease Characteristic
Type I HAE
|
35 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
108 Participants
n=4 Participants
|
|
Primary Disease Characteristic
Type II HAE
|
3 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Primary Disease Characteristic
Missing
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Up to 24 h after start of study treatmentPopulation: Analysis was based on the ITT population which included all subjects receiving any portion of the randomized study medication.
The start of symptom relief was determined by subject self-assessment. Time to start of symptom relief was set to 24 hours if the subject received rescue medication (blinded study medication, narcotic analgesics, antiemetics, open-label C1-INH, or fresh frozen plasma) at any time point after the start of study treatment but before start of relief.
Outcome measures
| Measure |
C1-INH 10 U/kg bw
n=39 Participants
Includes all subjects enrolled and randomized to the C1-INH 10 U/kg bw arm.
|
C1-INH 20 U/kg bw
n=43 Participants
Includes all subjects enrolled and randomized to the C1-INH 20 U/kg bw arm.
|
Placebo
n=42 Participants
Includes all subjects enrolled and randomized to the Placebo arm.
|
|---|---|---|---|
|
Time to Start of Relief of Symptoms From HAE Attack
|
1.17 Hours
Full Range 10.513 • Interval 0.17 to 24.0
|
0.5 Hours
Full Range 8.202 • Interval 0.17 to 24.0
|
1.5 Hours
Full Range 11.481 • Interval 0.2 to 24.0
|
SECONDARY outcome
Timeframe: Baseline and between 2 and 4 h after start of study treatmentPopulation: Analysis was based on the ITT population which included all subjects receiving any portion of the randomized study medication.
Includes any worsening of intensity of at least 1 of the HAE symptoms present at baseline. Routinely checked symptoms included pain, nausea, vomiting, cramps, and diarrhea.
Outcome measures
| Measure |
C1-INH 10 U/kg bw
n=39 Participants
Includes all subjects enrolled and randomized to the C1-INH 10 U/kg bw arm.
|
C1-INH 20 U/kg bw
n=43 Participants
Includes all subjects enrolled and randomized to the C1-INH 20 U/kg bw arm.
|
Placebo
n=42 Participants
Includes all subjects enrolled and randomized to the Placebo arm.
|
|---|---|---|---|
|
Number of Subjects With Worsened Intensity of Clinical HAE Symptoms
|
8 Subjects
|
2 Subjects
|
13 Subjects
|
SECONDARY outcome
Timeframe: Within 4 h after start of study treatmentPopulation: Analysis was based on the ITT population which included all subjects receiving any portion of the randomized study medication.
Outcome measures
| Measure |
C1-INH 10 U/kg bw
n=39 Participants
Includes all subjects enrolled and randomized to the C1-INH 10 U/kg bw arm.
|
C1-INH 20 U/kg bw
n=43 Participants
Includes all subjects enrolled and randomized to the C1-INH 20 U/kg bw arm.
|
Placebo
n=42 Participants
Includes all subjects enrolled and randomized to the Placebo arm.
|
|---|---|---|---|
|
Number of Vomiting Episodes
|
0 Episodes per subject
Full Range 0.77 • Interval 0.0 to 4.0
|
0 Episodes per subject
Full Range 0.41 • Interval 0.0 to 2.0
|
0 Episodes per subject
Full Range 2.59 • Interval 0.0 to 16.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 24 h after start of study treatmentPopulation: Analysis was based on the ITT population which included all subjects receiving any portion of the randomized study medication.
Complete resolution of symptoms was determined by subject self-assessment.
Outcome measures
| Measure |
C1-INH 10 U/kg bw
n=39 Participants
Includes all subjects enrolled and randomized to the C1-INH 10 U/kg bw arm.
|
C1-INH 20 U/kg bw
n=43 Participants
Includes all subjects enrolled and randomized to the C1-INH 20 U/kg bw arm.
|
Placebo
n=42 Participants
Includes all subjects enrolled and randomized to the Placebo arm.
|
|---|---|---|---|
|
Time to Complete Resolution of All HAE Symptoms, Including Pain
|
20.00 Hours
Full Range 494.230 • Interval 0.47 to 1486.17
|
4.92 Hours
Full Range 314.347 • Interval 0.47 to 1486.17
|
7.79 Hours
Full Range 382.815 • Interval 0.33 to 1486.17
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Within 4 h after start of study treatmentPopulation: Analysis was based on the ITT population which included all subjects receiving any portion of the randomized study medication.
Outcome measures
| Measure |
C1-INH 10 U/kg bw
n=39 Participants
Includes all subjects enrolled and randomized to the C1-INH 10 U/kg bw arm.
|
C1-INH 20 U/kg bw
n=43 Participants
Includes all subjects enrolled and randomized to the C1-INH 20 U/kg bw arm.
|
Placebo
n=42 Participants
Includes all subjects enrolled and randomized to the Placebo arm.
|
|---|---|---|---|
|
Number of Subjects Receiving Rescue Study Medication
|
13 Subjects
|
8 Subjects
|
24 Subjects
|
Adverse Events
C1-INH 10 U/kg bw
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
C1-INH 20 U/kg bw
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
C1-INH 10 U/kg bw
n=39 participants at risk
Includes subjects receiving 10 U/kg bw C1-INH and no rescue study medication within 4 hours after the start of the initial treatment.
|
C1-INH 20 U/kg bw
n=46 participants at risk
Includes subjects receiving 20 U/kg bw C1-INH and no rescue study medication within 4 hours after the start of the initial treatment (n=43). An additional 3 subjects not randomized to but treated with 20 U/kg bw C1-INH in this time period were also included in this group for the safety analysis.
|
Placebo
n=41 participants at risk
Includes subjects receiving Placebo and no rescue study medication within 4 hours after the start of the initial treatment.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
2.6%
1/39 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
4.3%
2/46 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
7.3%
3/41 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
|
Gastrointestinal disorders
Diarrhea
|
2.6%
1/39 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
0.00%
0/46 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
9.8%
4/41 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
|
Nervous system disorders
Dysgeusia
|
2.6%
1/39 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
4.3%
2/46 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
0.00%
0/41 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
|
General disorders
Edema peripheral
|
2.6%
1/39 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
2.2%
1/46 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
0.00%
0/41 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
|
General disorders
Face edema
|
2.6%
1/39 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
0.00%
0/46 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
2.4%
1/41 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
|
Nervous system disorders
Headache
|
2.6%
1/39 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
0.00%
0/46 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
4.9%
2/41 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
|
Gastrointestinal disorders
Lip swelling
|
2.6%
1/39 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
0.00%
0/46 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
2.4%
1/41 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
10.3%
4/39 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
2.2%
1/46 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
4.9%
2/41 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
|
Gastrointestinal disorders
Nausea
|
2.6%
1/39 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
6.5%
3/46 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
12.2%
5/41 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
|
General disorders
Pain
|
10.3%
4/39 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
2.2%
1/46 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
2.4%
1/41 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
|
Gastrointestinal disorders
Vomiting
|
2.6%
1/39 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
2.2%
1/46 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
7.3%
3/41 • AEs for each study arm are reported for the first 4 hours after start of study treatment.
Safety data were analyzed according to the actual treatment received. The analysis of AEs within 4 hours of the start of initial treatment permits an unbiased comparison of treatment groups without the confounding effect of any rescue medication.
|
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 public release. The sponsor may request any changes necessary to prevent forfeiture of patent rights to data not in the public domain. For a multi-center study, the investigator must wait (i) at least 1 year after the study is completed at all sites or (ii) until notified by the sponsor that no multi-center publication is planned before seeking publication review.
- Publication restrictions are in place
Restriction type: OTHER