Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study to Evaluate the Clinical Efficacy and Safety of Subcutaneously Administered C1 Esterase Inhibitor for the Prevention of Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02584959
Recruitment Status : Completed
First Posted : October 23, 2015
Results First Posted : November 28, 2018
Last Update Posted : May 10, 2019
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Condition Hereditary Angioedema (HAE)
Interventions Drug: C1 esterase inhibitor [human] liquid
Drug: Placebo
Enrollment 75
Recruitment Details This was a multicenter study conducted at 33 sites/centers in 7 countries: United States, Canada , Germany, Hungary, Israel, Spain, and Romania .
Pre-assignment Details Of the 81 participants screened, 6 subjects failed to meet the randomization criteria and were not randomly assigned to a treatment sequence . All 75 randomly assigned participants received at least 1 dose of the IP.
Arm/Group Title Experimental/Placebo Placebo/Experimental Experimental/ Experimental
Hide Arm/Group Description Participants were randomized to receive C1 Esterase Inhibitor in the 1st treatment period and then switched to Placebo in the 2nd treatment period. Participants were randomized to receive placebo treatment in the 1st treatment period and then switched to receive C1 Esterase Inhibitor in the 2nd treatment period. Participants were randomized to receive C1 Esterase Inhibitor in both 1st as well as the 2nd treatment period.
Period Title: Period 1
Started 31 29 15
Completed 28 25 15
Not Completed 3 4 0
Reason Not Completed
Withdrawn from study             3             4             0
Period Title: Period 2
Started 28 25 15
Completed 22 24 13
Not Completed 6 1 2
Reason Not Completed
Withdrawn from study             6             1             2
Arm/Group Title Experimental/Placebo Placebo/Experimental Experimental/ Experimental Total
Hide Arm/Group Description Subjects will be randomized to receive C1 Esterase Inhibitor in the 1st Treatment period and then switch to Placebo in the 2nd treatment period. Subjects will be randomized to receive a placebo treatment in the 1st Treatment period and then switch to receive C1 Esterase Inhibitor in the 2nd treatment period. Subjects will be randomized and receive C1 Esterase Inhibitor in both 1st as well as the 2nd treatment period Total of all reporting groups
Overall Number of Baseline Participants 31 29 15 75
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 29 participants 15 participants 75 participants
<=18 years
0
   0.0%
2
   6.9%
1
   6.7%
3
   4.0%
Between 18 and 65 years
30
  96.8%
25
  86.2%
13
  86.7%
68
  90.7%
>=65 years
1
   3.2%
2
   6.9%
1
   6.7%
4
   5.3%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 31 participants 29 participants 15 participants 75 participants
40.5  (13.16) 40.7  (15.34) 44.4  (16.40) 41.3  (14.58)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 29 participants 15 participants 75 participants
Female
23
  74.2%
21
  72.4%
8
  53.3%
52
  69.3%
Male
8
  25.8%
8
  27.6%
7
  46.7%
23
  30.7%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 29 participants 15 participants 75 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   3.4%
0
   0.0%
1
   1.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   3.2%
1
   3.4%
0
   0.0%
2
   2.7%
White
30
  96.8%
27
  93.1%
15
 100.0%
72
  96.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Time-Normalized Number of Attacks (NNA) for Participants During a Treatment Period
Hide Description

The angioedema attacks were recorded in the electronic patient diary. The investigator completed a separate angioedema eCRF for each attack based on the review of the patients diary.

Time-normalized number of angioedema attacks was expressed as the number of attacks per month (ie, 30.4 days) of exposure. NNA=30.4 * (number of attacks during treatment period) / (days of treatment period).

Time Frame Weeks 1 to 14 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected for the Experimental/Experimental Arm for this outcome measure and this represents the full analysis set.
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm and in period 2 of the Placebo/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 56 57
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Number of attacks
1.611
(1.067 to 2.156)
3.931
(3.391 to 4.471)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment C1 INH, Treatment Placebo
Comments The LS means, 95% CIs, and p-values were based on a mixed effect linear model with period, sequence ,use of prophylactic therapy with C1 INH at randomization, and treatment as fixed effects and subject nested within sequence as a random effect.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -2.320
Confidence Interval (2-Sided) 95%
-2.895 to -1.744
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Proportion of Participants Meeting at Least a 50% Reduction in NNA (Normalized Number of Angioedema Attacks) During the Experimental Injection Treatment Period Relative to the Placebo Period.
Hide Description The angioedema attacks were recorded in the electronic patient diary. The investigator completed a separate angioedema eCRF for each attack based on the review of the patients diary. Time-Normalized Number of Attacks was expressed as the number of attacks per month (ie, 30.4 days) of exposure. NNA = 30.4 x (number of attacks during treatment period) / (days of treatment period).
Time Frame Weeks 1 to 14 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis done on participants from the crossover sequences (Experimental/Placebo, Placebo/Experimental) who were dosed in both treatment periods. As the measure is implicitly a within subject comparison of the two arms the full analysis set is reported here. Participants with 0 attacks in the placebo period were excluded as %-reduct. not calculated
Arm/Group Title Full Analysis Set
Hide Arm/Group Description:
Including all participants in the cross-over sequences who had data in both treatment periods and who received at least one dose of C1 Esterase Inhibitor and had at least 1 post-baseline primary efficacy assessment.
Overall Number of Participants Analyzed 49
Measure Type: Count of Participants
Unit of Measure: Participants
38
  77.6%
3.Secondary Outcome
Title Time-Normalized Number of Attacks (NNA) for Participants During Each Treatment Period Excluding the First 2 Weeks.
Hide Description The angioedema attacks were recorded in the electronic patient diary. The investigator completed a separate angioedema eCRF for each attack based on the review of the patients diary. Time-normalized number of angioedema attacks was expressed as the number of attacks per month (ie, 30.4 days) of exposure. NNA=30.4 * (number of attacks during treatment period) / (days of treatment period).
Time Frame Weeks 3 to 14 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected for the Experimental/Experimental Arm for this outcome measure and this represents the full analysis set.
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm and in period 2 of the Placebo/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 55 55
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Number of Attacks
1.524
(0.912 to 2.136)
3.847
(3.237 to 4.457)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment C1 INH, Treatment Placebo
Comments The LS means, 95% CIs, and p-values were based on a mixed effect linear model with period, sequence ,use of prophylactic therapy with C1 INH at randomization, and treatment as fixed effects and subject nested within sequence as a random effect.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -2.323
Confidence Interval (2-Sided) 95%
-2.969 to -1.677
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Proportion of Participants Meeting at Least a 50% Reduction in NNA (Normalized Number of Angioedema Attacks) During the Experimental Injection Treatment Period Relative to the Placebo Period Excluding the First 2 Weeks of Each Treatment Period.
Hide Description The angioedema attacks were recorded in the electronic patient diary. The investigator completed a separate angioedema eCRF for each attack based on the review of the patients diary. Time-Normalized Number of Attacks was expressed as the number of attacks per month (ie, 30.4 days) of exposure. NNA = 30.4 x (number of attacks during treatment period) / (days of treatment period).
Time Frame Weeks 3 to 14 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis done on participants from the crossover sequences (Experimental/Placebo, Placebo/Experimental) who were dosed in both treatment periods. As the measure is implicitly a within subject comparison of the two arms the full analysis set is reported here. Participants with 0 attacks in the placebo period were excluded as %-reduct. not calculated
Arm/Group Title Full Analysis Data Set
Hide Arm/Group Description:
Including all participants in the cross-over sequences who had data in both treatment periods and who received at least one dose of C1 Esterase Inhibitor and had at least 1 post-baseline primary efficacy assessment.
Overall Number of Participants Analyzed 47
Measure Type: Count of Participants
Unit of Measure: Participants
36
  76.6%
5.Secondary Outcome
Title Proportion of Participants Meeting at Least a 50% Reduction in NNA (Normalized Number of Angioedema Attacks) During the Experimental Injection Treatment Period Relative to the Pre-treatment Assessment.
Hide Description The angioedema attacks were recorded in the electronic patient diary. The investigator completed a separate angioedema eCRF for each attack based on the review of the patients diary. Time-Normalized Number of Attacks was expressed as the number of attacks per month (ie, 30.4 days) of exposure. NNA = 30.4 x (number of attacks during treatment period) / (days of treatment period).
Time Frame Weeks 1 to 14 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set from the crossover sequences (Experimental/Placebo arm and Placebo/Experimental arm) was used for analysis of this outcome measure.Participants with zero attacks in the placebo period were excluded because a percent reduction could not be calculated. Analysis was done on participants with pretreatment and post-treatment NNA values
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm and in period 2 of the Placebo/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 53 55
Measure Type: Count of Participants
Unit of Measure: Participants
41
  77.4%
13
  23.6%
6.Secondary Outcome
Title Cumulative Attack Severity
Hide Description

Severity of the angioedema attack sign/symptom was characterized as None: no symptom; Mild: noticeable symptom but easily tolerated by the participant and did not interfere with routine activities; Moderate: symptom interfered with the participant’s ability to attend school or participate in family life and social/recreational activities; Severe: symptom significantly limited the participant’s ability to attend school or participate in family life and social/recreational activities.

Symptom severity score was assigned as Mild = 1, Moderate = 2 and Severe = 3. Cumulative attack severity score was the sum of the maximum symptom severity scores recorded for each angioedema attack in a treatment period.

Cumulative attack-severity score normalized per month [(raw score/number of days of participation in that treatment period)*30.4] was reported here. Cumulative attack-severity score normalized per month ranged from 0 to 19.83 and higher scores represent worse symptoms.

Time Frame Weeks 1 to 14 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected for the Experimental/Experimental Arm for this outcome measure and this represents the full analysis set.
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm and in period 2 of the Placebo/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 56 57
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a scale
3.159
(1.856 to 4.463)
8.041
(6.746 to 9.336)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment C1 INH, Treatment Placebo
Comments The LS means, 95% CIs, and p-values were based on a mixed effect linear model with period, sequence ,use of prophylactic therapy with C1 INH at randomization, and treatment as fixed effects and subject nested within sequence as a random effect.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -4.881
Confidence Interval (2-Sided) 95%
-6.113 to -3.649
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Number of Attack-free Days
Hide Description Attack free days were normalized per month.
Time Frame Weeks 1 to 14 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected for the Experimental/Experimental Arm for this outcome measure and this represents the full analysis set.
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm and in period 2 of the Placebo/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 56 57
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Days
26.788
(25.106 to 28.470)
21.353
(19.681 to 23.025)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment C1 INH, Treatment Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 5.435
Confidence Interval (2-Sided) 95%
3.981 to 6.889
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number of Angioedema Attacks Requiring Acute Treatment
Hide Description Angioedema attacks were normalized per month.
Time Frame Weeks 1 to 14 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected for the Experimental/Experimental Arm for this outcome measure and this represents the full analysis set.
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm and in period 2 of the Placebo/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 56 57
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Number of attacks
1.454
(0.906 to 2.002)
3.628
(3.085 to 4.172)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment C1 INH, Treatment Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -2.175
Confidence Interval (2-Sided) 95%
-2.750 to -1.599
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Response to Icatibant When Administered for an Acute Attack
Hide Description The number of Acute Hereditary Angioedema Attacks that required Icatibant as acute therapy is presented by the number of Icatibant injections.
Time Frame Weeks 1 to 14 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
For treatment with C1 INH (Overall treatment with C1 INH group) all participants who received C1 INH in each of the randomized arms (experimental/placebo, placebo/experimental and experimental/experimental) are included.
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm, in period 2 of the Placebo/Experimental arm and in period 1 and 2 of the Experimental/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 71 57
Overall Number of Units Analyzed
Type of Units Analyzed: Attacks requiring Icatibant
181 453
Count of Units
Unit of Measure: Attacks requiring Icatibant
requiring 1 injection
129
  71.3%
306
  67.5%
requiring 2 injections
38
  21.0%
89
  19.6%
requiring 3 injections
13
   7.2%
30
   6.6%
requiring >= 4 injections
1
   0.6%
28
   6.2%
10.Secondary Outcome
Title Number of Patients With Adverse Events (AEs)
Hide Description Treatment-emergent adverse events (TEAE) were counted by the treatment most recently taken when the event occurred. Participants were counted once per category per treatment.
Time Frame Weeks 1 to 14 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm, in period 2 of the Placebo/Experimental arm and in period 1 and 2 of the Experimental/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 71 57
Measure Type: Count of Participants
Unit of Measure: Participants
Any TEAE
42
  59.2%
32
  56.1%
Serious TEAE
2
   2.8%
3
   5.3%
Severe TEAE
4
   5.6%
3
   5.3%
TEAE within 24 hours of IP administration
10
  14.1%
7
  12.3%
Serious TEAE within 24 hours of IP administration
0
   0.0%
0
   0.0%
Treatment-related TEAE within 24 hrs of IP admin.
3
   4.2%
2
   3.5%
Treatment-related SAE within 24 hrs of IP admin.
0
   0.0%
0
   0.0%
TEAE within 24 hrs IP admin. leading to withdrawal
1
   1.4%
0
   0.0%
Deaths due to TEAE
0
   0.0%
0
   0.0%
Hospitalizations due to TEAE
2
   2.8%
3
   5.3%
TEAE leading to withdrawal
1
   1.4%
2
   3.5%
Treatment-related TEAE
5
   7.0%
4
   7.0%
Treatment-related SAE
0
   0.0%
0
   0.0%
Treatment-related severe TEAE
0
   0.0%
0
   0.0%
Treatment-related TEAE leading to withdrawal
1
   1.4%
0
   0.0%
11.Secondary Outcome
Title Number of Participants With Injection Site Reactions
Hide Description Injection site reactions (Erythema, Swelling, Cutaneous pain, Burning sensation, Itching/Pruritus, Warm sensation) were recorded on a designated eCRF page by the site personnel who monitored the local reaction for 1 hour after IP administration 5 times during each treatment period.
Time Frame Weeks 1 to 14 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm, in period 2 of the Placebo/Experimental arm and in period 1 and 2 of the Experimental/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 71 57
Measure Type: Count of Participants
Unit of Measure: Participants
Any injection site reaction
42
  59.2%
15
  26.3%
Any severe injection site reaction
2
   2.8%
0
   0.0%
Any mild injection site reaction
42
  59.2%
15
  26.3%
Any moderate injection site reaction
14
  19.7%
1
   1.8%
12.Secondary Outcome
Title Number of Patients With Positive Anti-C1 INH Antibodies
Hide Description Anti-C1 INH antibodies were measured during study time.
Time Frame Weeks 1 to 14 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm, in period 2 of the Placebo/Experimental arm and in period 1 and 2 of the Experimental/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 71 57
Measure Type: Count of Participants
Unit of Measure: Participants
Positive anti-C1 INH antibodies prior treatment
0
   0.0%
0
   0.0%
Positive anti-C1 INH antibodies developed
0
   0.0%
0
   0.0%
13.Secondary Outcome
Title PK Parameters: AUC (0-96) and AUC (0-t) for Functional C1 INH Binding Activity
Hide Description AUC(0-96)=area under the plasma concentration-time curve from time zero to last measurable concentration; AUC(0-t)=area under the plasma concentration-time curve from time zero extrapolated to the end of the dosing interval tau, where tau is approximately 84 hours (ie, average of every 3 or 4 days) AUC(0-96) = AUC(0-tau).
Time Frame Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2. In addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants included who have taken at least one dose of investigational product and for whom the primary PK data are considered sufficient and interpretable.
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm, in period 2 of the Placebo/Experimental arm and in period 1 and 2 of the Experimental/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 6 3
Mean (Standard Deviation)
Unit of Measure: mU*h/mL
AUC (0-96) 31070  (17396) 13860  (7269.0)
AUC (0-t) 31190  (17389) 13860  (7268.3)
14.Secondary Outcome
Title PK Parameters: AUC (0-96) and AUC (0-t) for C1 INH Antigen Concentrations
Hide Description AUC(0-96)=area under the plasma concentration-time curve from time zero to last measurable concentration; AUC(0-t)=area under the plasma concentration-time curve from time zero extrapolated to the end of the dosing interval tau, where tau is approximately 84 hours (ie, average of every 3 or 4 days) AUC(0-96) = AUC(0-tau).
Time Frame Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2. In addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants included who have taken at least one dose of investigational product and for whom the primary PK data are considered sufficient and interpretable.
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm, in period 2 of the Placebo/Experimental arm and in period 1 and 2 of the Experimental/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 6 3
Mean (Standard Deviation)
Unit of Measure: mcg*h/mL
AUC (0-96) 6882  (4586.0) 1849  (426.36)
AUC (0-t) 6902  (4574.0) 1849  (426.09)
15.Secondary Outcome
Title PK Parameters: AUC (0-96) and AUC (0-t) for Complement C4 Concentrations (Treamtment C1 INH)
Hide Description AUC(0-96)=area under the plasma concentration-time curve from time zero to last measurable concentration; AUC(0-t)=area under the plasma concentration-time curve from time zero extrapolated to the end of the dosing interval tau, where tau is approximately 84 hours (ie, average of every 3 or 4 days) AUC(0-96) = AUC(0-tau).
Time Frame Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2. In addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants included who have taken at least one dose of investigational product and for whom the primary PK data are considered sufficient and interpretable.
Arm/Group Title Treatment C1 INH
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm, in period 2 of the Placebo/Experimental arm and in period 1 and 2 of the Experimental/Experimental arm).
Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: mg*h/L
AUC (0-96) 16690  (803.60)
AUC (0-t) 16780  (895.63)
16.Secondary Outcome
Title PK Parameters: AUC (0-96) and AUC (0-t) for Complement C4 Concentrations (Treatment Placebo)
Hide Description AUC(0-96)=area under the plasma concentration-time curve from time zero to last measurable concentration; AUC(0-t)=area under the plasma concentration-time curve from time zero extrapolated to the end of the dosing interval tau, where tau is approximately 84 hours (ie, average of every 3 or 4 days) AUC(0-96) = AUC(0-tau). Participant wise data was reported for this outcome.
Time Frame Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2. In addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants included who have taken at least one dose of investigational product and for whom the primary PK data are considered sufficient and interpretable. No summary analysis was done and participant wise data are reported.
Arm/Group Title Treatment Placebo
Hide Arm/Group Description:
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: mg*h/L
AUC (0-96) - Participant 1 8840
AUC (0-96) - Participant 2 2150
AUC (0-t) - Participant 1 8840
AUC (0-t) - Participant 2 2150
17.Secondary Outcome
Title PK Parameters: Cmax and Cmin for Functional C1 INH Binding Activity
Hide Description Cmax=maximum observed plasma concentration and Cmin=minimum observed plasma concentration
Time Frame Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2 and in addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants included who have taken at least one dose of investigational product and for whom the primary PK data are considered sufficient and interpretable.
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm, in period 2 of the Placebo/Experimental arm and in period 1 and 2 of the Experimental/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 6 3
Mean (Standard Deviation)
Unit of Measure: mU/mL
Cmax 396.20  (273.013) 159.50  (82.982)
Cmin 258.15  (138.232) 125.90  (62.329)
18.Secondary Outcome
Title PK Parameters: Cmax and Cmin for C1 INH Antigen Concentrations
Hide Description Cmax=maximum observed plasma concentration and Cmin=minimum observed plasma concentration
Time Frame Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2 and in addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2
Hide Outcome Measure Data
Hide Analysis Population Description
All participants included who have taken at least one dose of investigational product and for whom the primary PK data are considered sufficient and interpretable.
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm, in period 2 of the Placebo/Experimental arm and in period 1 and 2 of the Experimental/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm)..
Overall Number of Participants Analyzed 6 3
Mean (Standard Deviation)
Unit of Measure: µg/mL
Cmax 77.680  (52.4375) 21.257  (5.1647)
Cmin 65.562  (45.9331) 17.913  (4.4316)
19.Secondary Outcome
Title PK Parameters: Cmax and Cmin for Complement C4 Concentrations (Treatment C1 INH)
Hide Description Cmax=maximum observed plasma concentration and Cmin=minimum observed plasma concentration
Time Frame Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2 and in addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants included who have taken at least one dose of investigational product and for whom the primary PK data are considered sufficient and interpretable.
Arm/Group Title Treatment C1 INH
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm, in period 2 of the Placebo/Experimental arm and in period 1 and 2 of the Experimental/Experimental arm).
Overall Number of Participants Analyzed 5
Mean (Standard Deviation)
Unit of Measure: mg/L
Cmax 200  (30.82)
Cmin 158  (13.04)
20.Secondary Outcome
Title PK Parameters: Cmax and Cmin for Complement C4 Concentrations (Treatment Placebo)
Hide Description

Cmax=maximum observed plasma concentration and Cmin=minimum observed plasma concentration.

Participant wise data was reported for this outcome.

Time Frame Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2 and in addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants included who have taken at least one dose of investigational product and for whom the primary PK data are considered sufficient and interpretable. No summary analysis was done and participant wise data are reported.
Arm/Group Title Treatment Placebo
Hide Arm/Group Description:
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: mg/L
Cmax - Participant 1 120
Cmax - Participant 2 27
Cmin - Participant 1 82
Cmin - Participant 2 18
21.Secondary Outcome
Title PK Parameters: Tmax
Hide Description tmax=time of maximum observed plasma concentration
Time Frame Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2 and in addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
Hide Outcome Measure Data
Hide Analysis Population Description

All participants included who have taken at least one dose of investigational product and for whom the primary PK data are considered sufficient and interpretable.

For Complement C4 Concentration no summary analysis was done for participants in the placebo group and participant wise data for 2 participants are reported in Outcome measure #19.

Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm, in period 2 of the Placebo/Experimental arm and in period 1 and 2 of the Experimental/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 6 3
Mean (Standard Deviation)
Unit of Measure: hours
Functional C1 INH Binding Activity Number Analyzed 6 participants 3 participants
31.597  (12.7038) 55.689  (49.4851)
C1 INH Antigen Concentration Number Analyzed 6 participants 3 participants
31.656  (24.6912) 47.578  (47.3106)
Complement C4 Concentration Number Analyzed 5 participants 0 participants
33.417  (36.5183)
22.Secondary Outcome
Title PK Parameters: Tmax for Complement C4 Concentrations (Placebo Group)
Hide Description tmax=time of maximum observed plasma concentration. Participant wise data was reported for this outcome.
Time Frame Within 15 min prior dosing at week 1, week 2, week 8, week 16, week 24, week 27/28 and 48 (± 3) hours after dose in week 27/28 in period 1 and 2 and in addition 24 (±3) hours, 72 (±6) hours and 96 (±6) hours post dose in week 28 for period 2.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants included who have taken at least one dose of investigational product and for whom the primary PK data are considered sufficient and interpretable. No summary analysis was done and participant wise data are reported.
Arm/Group Title Treatment Placebo
Hide Arm/Group Description:
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: mg/L
tmax - Participant 1 94.62
tmax - Participant 2 48.12
23.Secondary Outcome
Title Assess Disease Activity as Measured by the Angioedema Activity Score (AAS) Normalized Per Month
Hide Description Disease activity was measured using a 98-day Angioedema Activity Score (AAS). The AAS collects information of disease activity in the last 24 hours. The following items are assessed: experience of swelling, severity of the swelling, timing of the swelling, extent of discomfort due to the swelling, extent that the swelling caused limitations in daily life, and feelings of being disfigured by the swelling. The instrument uses a binary response option for the first item and a three-point response scale for the 5 items thereafter. The daily AAS was the sum of the AAS items per day. Total daily ASS scores range between 0 and 15 points. Higher values stand for higher disease activity. The normalized 98-day AAS per month for a participant is calculated by (the sum of daily AAS within a treatment period/the number of days that a subject has AAS records within the treatment period)*30.4.
Time Frame Weeks 1 to 14 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected for the Experimental/Experimental Arm for this outcome measure and this represents the full analysis set.
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm and in period 2 of the Placebo/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 56 57
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score on a scale
25.433
(11.204 to 39.662)
57.168
(43.010 to 71.326)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment C1 INH, Treatment Placebo
Comments The Least Square means, 95% confidence intervals and p-values are based on mixed effect linear model with period, sequence, use of prophylactic therapy with C1 INH at randomization and treatment as fixed effects and subject nested within sequence as a random effect.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -31.735
Confidence Interval (2-Sided) 95%
-42.696 to -20.773
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Participant Experience With Self-administration: Overall Experience With the Syringe
Hide Description Self-administration survey with questions about the overall experience with the syringe was assessed in week 14 (visit 28 and 28b). Visit 28 summarizes treatment period 1 of the experimental/experimental arm and treatment periods 1 and 2 of the experimental/placebo arm and the placebo/experimental arm. Visit 28b summarizes treatment period 2 of the experimental/experimental arm.
Time Frame Week 14 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
Visit 28b summarizes only treatment period 2 of the Experimental/Experimental arm. Therefore no participants were analyzed in the placebo group.
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm, in period 2 of the Placebo/Experimental arm and in period 1 and 2 of the Experimental/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 59 40
Measure Type: Count of Participants
Unit of Measure: Participants
Visit 28: Easy to use Number Analyzed 59 participants 40 participants
48
  81.4%
36
  90.0%
Visit 28: Somewhat difficult to use Number Analyzed 59 participants 40 participants
11
  18.6%
4
  10.0%
Visiti 28: Difficult to use Number Analyzed 59 participants 40 participants
0
   0.0%
0
   0.0%
Visit 28b: Easy to use Number Analyzed 12 participants 0 participants
11
  91.7%
Visit 28b: Somewhat difficult to use Number Analyzed 12 participants 0 participants
1
   8.3%
Visiti 28b: Difficult to use Number Analyzed 12 participants 0 participants
0
   0.0%
25.Secondary Outcome
Title Participant Experience With Self-administration: How Many Visits for Confidence With Self-administration
Hide Description

The self-administration survey includes the number of visits needed for participants to be able to self-administer investigational product with confidence and all participants could self-administer without supervision.

Visit 28 summarizes treatment period 1 of the experimental/experimental arm and treatment periods 1 and 2 of the experimental/placebo arm and the placebo/experimental arm. Visit 28b summarizes treatment period 2 of the experimental/experimental arm.

Time Frame Week 14 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
Visit 28b summarizes only treatment period 2 of the Experimental/Experimental arm. Therefore no participants were analyzed in the placebo group.
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm, in period 2 of the Placebo/Experimental arm and in period 1 and 2 of the Experimental/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 59 40
Mean (Standard Deviation)
Unit of Measure: Number of visits
Visit 28 Number Analyzed 59 participants 40 participants
1.8  (1.70) 2.0  (2.49)
Visit 28b Number Analyzed 12 participants 0 participants
1.8  (1.22)
26.Secondary Outcome
Title Participant Experience With Self-administration: Better Long-term Option and Preferred Administration
Hide Description

The self-administration survey includes the number of visits needed for participants to be able to self-administer investigational product with confidence and all participants could self-administer without supervision.

Visit 28 summarizes treatment period 1 of the experimental/experimental arm and treatment periods 1 and 2 of the experimental/placebo arm and the placebo/experimental arm. Visit 28b summarizes treatment period 2 of the experimental/experimental arm.

Time Frame Week 14 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
Visit 28b summarizes only treatment period 2 of the Experimental/Experimental arm. Therefore no participants were analyzed in the placebo group.
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description:
Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm, in period 2 of the Placebo/Experimental arm and in period 1 and 2 of the Experimental/Experimental arm).
Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
Overall Number of Participants Analyzed 59 40
Measure Type: Count of Participants
Unit of Measure: Participants
Visit 28: SC better long term option Number Analyzed 59 participants 40 participants
57
  96.6%
39
  97.5%
Visit 28: IV better long term option Number Analyzed 59 participants 40 participants
2
   3.4%
1
   2.5%
Visit 28: SC preferred administration Number Analyzed 59 participants 40 participants
56
  94.9%
40
 100.0%
Visit 28: IV preferred administration Number Analyzed 59 participants 40 participants
3
   5.1%
0
   0.0%
Visit 28: Preference for admin - very strong Number Analyzed 59 participants 40 participants
47
  79.7%
33
  82.5%
Visit 28: Preference for admin - fairly strong Number Analyzed 59 participants 40 participants
12
  20.3%
6
  15.0%
Visit 28: Preference for admin - not very strong Number Analyzed 59 participants 40 participants
0
   0.0%
1
   2.5%
Visit 28b: SC better long term option Number Analyzed 12 participants 0 participants
12
 100.0%
Visit 28b: IV better long term option Number Analyzed 12 participants 0 participants
0
   0.0%
Visit 28b: SC preferred administration Number Analyzed 12 participants 0 participants
11
  91.7%
Visit 28b: IV preferred administration Number Analyzed 12 participants 0 participants
1
   8.3%
Visit 28b: Preference for admin - very strong Number Analyzed 12 participants 0 participants
11
  91.7%
Visit 28b: Preference for admin - fairly strong Number Analyzed 12 participants 0 participants
0
   0.0%
Visit 28b: Preference for admin - not very strong Number Analyzed 12 participants 0 participants
1
   8.3%
27.Secondary Outcome
Title Mean Change in Angioedema Quality of Life Questionnaire Scores From Baseline to Week 13
Hide Description The AE-QoL is a questionnaire on the quality of life of patients suffering from recurrent angioedema. It consists of 17 specific questions that are associated with work, physical activity, free time, social relations, and food. Each of the 17 questions has a five-point response scale ranging from 1 (Never) to 5 (Very Often). The AE-QoL consists of 4 dimensions (functioning=4 questions(qns) fatigue/mood=5 qns, fears/shame=6 qns, nutrition=2 qns) and a total score (all 17 questions).All scores were calculated by using the following formula: (Σ items – min Σ items / max Σ items – min Σ items) x 100. Σ items=sum of response by participant, min Σ items=minimum response possible, max Σ items=maximum response possible. Scores range from 0 to 100 , with higher scores indicating greater impairment. Absolute change calculated as visit score at week 13 minus score at baseline per period.
Time Frame Baseline to week 13 for treatment period 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Experimental/Placebo Arm - Treatment C1 INH Experimental/Placebo Arm - Treatment Placebo Placebo/Experimental Arm - Treatment Placebo Placebo/Experimental Arm - Treatment C1 INH Experimental/Experimental Arm - Period 1 Treatment C1 INH Experimental/Experimental Arm - Period 2 Treatment C1 INH
Hide Arm/Group Description:
Participants randomized to the Experimental/Placebo arm received C1 Esterase Inhibitor (C1 INH) in treatment period 1.
Participants randomized to the Experimental/Placebo arm received Placebo in treatment period 2.
Participants randomized to the Placebo/Experimental arm received Placebo in treatment period 1.
Participants randomized to the Placebo/Experimental arm received C1 Esterase Inhibitor (C1 INH) in treatment period 2.
Participants randomized to the Experimental/Experimental arm received C1 Esterase Inhibitor (C1 INH) in treatment period 1.
Participants randomized to the Experimental/Experimental arm received C1 Esterase Inhibitor (C1 INH) in treatment period 2.
Overall Number of Participants Analyzed 31 28 29 25 15 15
Mean (Standard Deviation)
Unit of Measure: Mean change in AE-QoL scores
AE-QoL Total -10.35  (17.75) 4.77  (12.14) -6.86  (10.72) -12.10  (9.83) -11.65  (9.87) -0.52  (6.58)
Functioning -9.25  (21.29) 6.11  (20.62) -10.56  (17.23) -23.33  (19.45) -20.50  (14.62) -2.78  (10.34)
Fatigue/Mood -8.40  (21.94) 2.44  (14.20) -9.11  (10.16) -10.10  (13.42) -8.40  (12.29) 3.11  (9.33)
Fear/Shame -12.50  (21.46) 5.19  (12.06) -1.67  (10.62) -5.40  (10.67) -9.67  (11.91) -1.85  (11.19)
Nutrition -11.00  (22.45) 6.67  (19.70) -9.44  (25.55) -14.76  (17.50) -8.00  (16.19) -1.11  (7.82)
Time Frame Adverse events were reported from the time the informed consent was signed through 7 days afer the last dose of investigational product was received (week 1 to 15 for treatment period 1 and 2).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment C1 INH Treatment Placebo
Hide Arm/Group Description Participants who received C1 Esterase Inhibitor (C1 INH) treatment (in period 1 of the Experimental/Placebo arm, in period 2 of the Placebo/Experimental arm and in period 1 and 2 of the Experimental/Experimental arm). Participants who received Placebo treatment (in period 2 of the Experimental/Placebo arm and in period 1 of the Placebo/Experimental arm).
All-Cause Mortality
Treatment C1 INH Treatment Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/71 (0.00%)      0/57 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment C1 INH Treatment Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/71 (2.82%)      3/57 (5.26%)    
Cardiac disorders     
Cardiac arrest * 1  0/71 (0.00%)  0 1/57 (1.75%)  1
Congenital, familial and genetic disorders     
Hereditary angioedema * 1  0/71 (0.00%)  0 1/57 (1.75%)  1
Hepatobiliary disorders     
Cholelithiasis * 1  0/71 (0.00%)  0 1/57 (1.75%)  1
Infections and infestations     
Appendicitis * 1  1/71 (1.41%)  1 0/57 (0.00%)  0
Staphylococcal infection * 1  1/71 (1.41%)  1 0/57 (0.00%)  0
1
Term from vocabulary, MedDRA 19.0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment C1 INH Treatment Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/71 (32.39%)      14/57 (24.56%)    
Infections and infestations     
Viral upper respiratory tract infection * 1  11/71 (15.49%)  11 3/57 (5.26%)  3
Upper respiratory tract infection * 1  7/71 (9.86%)  7 4/57 (7.02%)  4
Injury, poisoning and procedural complications     
Contusion * 1  0/71 (0.00%)  0 3/57 (5.26%)  3
Nervous system disorders     
Headache * 1  6/71 (8.45%)  10 6/57 (10.53%)  7
1
Term from vocabulary, MedDRA 19.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Shire
Phone: +1 866 842 5335
EMail: ClinicalTransparency@shire.com
Layout table for additonal information
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT02584959     History of Changes
Other Study ID Numbers: SHP616-300
First Submitted: October 20, 2015
First Posted: October 23, 2015
Results First Submitted: July 17, 2018
Results First Posted: November 28, 2018
Last Update Posted: May 10, 2019