Hereditary Angioedema
Conditions
Brief summary
This is a multicenter, double-blind, randomized, placebo-controlled, parallel-arm study to investigate the efficacy and safety of subcutaneous administration of CSL312 (garadacimab) in the prophylactic treatment of hereditary angioedema.
Interventions
BIOLOGICALCSL312
Fully human immunoglobulin G subclass 4/lambda recombinant monoclonal antibody
DRUGPlacebo
Buffer without active ingredient
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female ≥ 12 years of age; diagnosed with clinically confirmed C1-INH hereditary angioedema; experience ≥ 3 attacks during the 3 months before screening. Note: For subjects taking any prophylactic HAE therapy during the 3 months before Screening, ≥ 3 HAE attacks may be documented over 3 consecutive months before commencing the prophylactic therapy.
Exclusion criteria
* Concomitant diagnosis of another form of angioedema such as idiopathic or acquired angioedema, recurrent angioedema associated with urticarial or hereditary angioedema type 3
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-Normalized Number of Hereditary Angioedema (HAE) Attacks Per Month During Treatment Period | First injection up to 6 months | Time-normalized number of HAE attacks per month during treatment was calculated per participant as: \[number of HAE attacks / length of participant treatment in days\] \* 30.4375. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time-Normalized Number of HAE Attacks Per Month Requiring On-Demand Treatment | 6 months, first 3-months and second 3-months of treatment period | Time-normalized number of HAE attacks per month requiring on-demand treatment was calculated per participant as: \[number of HAE attacks requiring on-demand treatment / length of participant in days\] \* 30.4375. |
| Time-Normalized Number of Moderate or Severe HAE Attacks Per Month | 6 months, first 3-months and second 3-months of treatment period | Time-normalized number of moderate or severe HAE attacks per month during treatment period was calculated per participant as: \[number of moderate or severe HAE attacks / length of participant treatment in days\] \* 30.4375. |
| Time-normalized Number of HAE Attacks Per Month in the First 3-months and Second 3-months of Treatment Period | First 3-months and second 3-months of treatment period | Time-normalized number of HAE attacks per month during treatment was calculated per participant as: \[number of HAE attacks / length of participant treatment in days\] \* 30.4375. |
| Relative Difference in Means in the Time-Normalized Number of HAE Attacks Per Month Between CSL312 to Placebo | 6 months, first 3-months and second 3-months of treatment period | Relative difference in means in the time-normalized number of HAE attacks per month CSL312 to Placebo was calculated as: 100 \* \[(mean time-normalized number of HAE attacks for CSL312 - mean time-normalized number of HAE attacks for placebo) / mean time-normalized number of HAE attacks for placebo\]. Time-normalized number of HAE attacks per month during treatment was calculated per participant as: \[number of HAE attacks / length of participant treatment in days\] \* 30.4375. |
| Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) | Up to 6 months | SGART is a self-assessment by the participant and measures the subject's overall treatment response to the investigational product using the following ratings: 0 (none: worse or no response at all, not acceptable), 1 (poor: very little response, not acceptable), 2 (fair: some response, acceptable but could be better), 3 (good: good response, acceptable), and 4 (excellent: excellent response, as good as can be imagined). |
| Percentage Change in the Time-normalized Number of HAE Attacks Per Month During the Treatment Period Compared to the Run-in Period | 6 months, first 3-months and second 3-months of treatment period | Percentage change in the time-normalized number of HAE attacks was calculated within a participant as: 100 \* \[1 - (time-normalized number of HAE attacks per month during treatment period / time-normalized number of HAE attacks per month during run-in period)\]. Time-normalized number of HAE attacks per month during treatment period was calculated per participant as: \[number of HAE attacks / length of participant treatment in days\] \* 30.4375. |
| Number of Participants With CSL312-induced Anti-CSL312 Antibodies | Up to 8 months | — |
| Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as Treatment Emergent Adverse Events (TEAEs) | From first dose of study drug up to 3 months after the last injection (approximately 8 months) | Laboratory assessments included: Hematology, biochemistry, urinalysis, and coagulation parameters. |
| Percentage of Participants With at Least One AE, SAE, and AESI | From first dose of study drug up to 3 months after the last injection (approximately 8 months) | AE is any untoward medical occurrence in a participant administered with an investigational product which does not necessarily have a causal relationship with treatment, can be any unfavorable and unintended sign, symptom, or disease temporally associated with use of an investigational product, whether or not considered related to product. SAE is any untoward medical occurrence that results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event. An AESI is an AE of scientific and medical concern specific to sponsor's product or program, for which ongoing monitoring and rapid communication by investigator to sponsor is appropriate. |
| Percentage of Participants With CSL312-induced Anti-CSL312 Antibodies | Up to 6 months | — |
| Percentage of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as TEAEs | From first dose of study drug up to 3 months after the last injection (approximately 8 months) | Laboratory assessments included: Hematology, biochemistry, urinalysis, and coagulation parameters. |
| Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI) | From first dose of study drug up to 3 months after the last injection (approximately 8 months) | AE is any untoward medical occurrence in a participant administered with an investigational product which does not necessarily have a causal relationship with treatment, can be any unfavorable and unintended sign, symptom, or disease temporally associated with use of an investigational product, whether or not considered related to product. SAE is any untoward medical occurrence that results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event. An AESI is an AE of scientific and medical concern specific to sponsor's product or program, for which ongoing monitoring and rapid communication by investigator to sponsor is appropriate. |
Countries
Canada, Germany, Hungary, Israel, Japan, Netherlands, United States
Participant flow
Recruitment details
Participants were enrolled at study centers in Canada, Germany, Hungary, Israel, Japan, Netherlands, and the United States from 27 January 2021 to 07 June 2022.
Pre-assignment details
A total of 80 participants were screened, of which 64 participants were randomized and received the loading dose in the treatment period.
Participants by arm
| Arm | Count |
|---|---|
| CSL312 Participants received a CSL312 loading dose of 400 mg as two 200 mg SC injections in Month 1 along with CSL312 of 200 mg SC injections, once monthly from Months 2 to 6. | 39 |
| Placebo Participants received a CSL312 matched loading dose of placebo as two SC injections in Month 1 along with CSL312 matched placebo SC injections, once monthly from Months 2 to 6. | 25 |
| Total | 64 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Total | Placebo | CSL312 |
|---|---|---|---|
| Age, Continuous | 41.2 years STANDARD_DEVIATION 15.92 | 37.8 years STANDARD_DEVIATION 12.8 | 43.3 years STANDARD_DEVIATION 17.45 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 60 Participants | 23 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 6 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 55 Participants | 22 Participants | 33 Participants |
| Region of Enrollment Canada | 8 participants | 3 participants | 5 participants |
| Region of Enrollment Germany | 15 participants | 8 participants | 7 participants |
| Region of Enrollment Hungary | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Israel | 9 participants | 2 participants | 7 participants |
| Region of Enrollment Japan | 6 participants | 2 participants | 4 participants |
| Region of Enrollment Netherlands | 3 participants | 1 participants | 2 participants |
| Region of Enrollment United States | 21 participants | 9 participants | 12 participants |
| Sex: Female, Male Female | 38 Participants | 14 Participants | 24 Participants |
| Sex: Female, Male Male | 26 Participants | 11 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 25 |
| other Total, other adverse events | 17 / 39 | 12 / 25 |
| serious Total, serious adverse events | 1 / 39 | 0 / 25 |
Outcome results
Primary
Time-Normalized Number of Hereditary Angioedema (HAE) Attacks Per Month During Treatment Period
Time-normalized number of HAE attacks per month during treatment was calculated per participant as: \[number of HAE attacks / length of participant treatment in days\] \* 30.4375.
Time frame: First injection up to 6 months
Population: ITT analysis set included all the randomized participants who provided written informed consent and underwent study screening procedures. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CSL312 | Time-Normalized Number of Hereditary Angioedema (HAE) Attacks Per Month During Treatment Period | 0.27 number of HAE attacks per month | Standard Deviation 0.683 |
| Placebo | Time-Normalized Number of Hereditary Angioedema (HAE) Attacks Per Month During Treatment Period | 2.01 number of HAE attacks per month | Standard Deviation 1.341 |
p-value: <0.001Two-sided Wilcoxon test
Secondary
Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI)
AE is any untoward medical occurrence in a participant administered with an investigational product which does not necessarily have a causal relationship with treatment, can be any unfavorable and unintended sign, symptom, or disease temporally associated with use of an investigational product, whether or not considered related to product. SAE is any untoward medical occurrence that results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event. An AESI is an AE of scientific and medical concern specific to sponsor's product or program, for which ongoing monitoring and rapid communication by investigator to sponsor is appropriate.
Time frame: From first dose of study drug up to 3 months after the last injection (approximately 8 months)
Population: Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CSL312 | Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI) | AE | 25 Participants |
| CSL312 | Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI) | SAE | 1 Participants |
| CSL312 | Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI) | AESI | 0 Participants |
| Placebo | Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI) | AE | 15 Participants |
| Placebo | Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI) | SAE | 0 Participants |
| Placebo | Number of Participants With at Least One Adverse Event (AE), Serious Adverse Event (SAE), and AEs of Special Interest (AESI) | AESI | 0 Participants |
Secondary
Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as Treatment Emergent Adverse Events (TEAEs)
Laboratory assessments included: Hematology, biochemistry, urinalysis, and coagulation parameters.
Time frame: From first dose of study drug up to 3 months after the last injection (approximately 8 months)
Population: Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CSL312 | Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as Treatment Emergent Adverse Events (TEAEs) | 1 Participants |
| Placebo | Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as Treatment Emergent Adverse Events (TEAEs) | 2 Participants |
Secondary
Number of Participants With CSL312-induced Anti-CSL312 Antibodies
Time frame: Up to 8 months
Population: Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CSL312 | Number of Participants With CSL312-induced Anti-CSL312 Antibodies | 1 Participants |
| Placebo | Number of Participants With CSL312-induced Anti-CSL312 Antibodies | 0 Participants |
Secondary
Percentage Change in the Time-normalized Number of HAE Attacks Per Month During the Treatment Period Compared to the Run-in Period
Percentage change in the time-normalized number of HAE attacks was calculated within a participant as: 100 \* \[1 - (time-normalized number of HAE attacks per month during treatment period / time-normalized number of HAE attacks per month during run-in period)\]. Time-normalized number of HAE attacks per month during treatment period was calculated per participant as: \[number of HAE attacks / length of participant treatment in days\] \* 30.4375.
Time frame: 6 months, first 3-months and second 3-months of treatment period
Population: ITT analysis set included all the randomized participants who provided written informed consent and underwent study screening procedures. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL312 | Percentage Change in the Time-normalized Number of HAE Attacks Per Month During the Treatment Period Compared to the Run-in Period | 6 Months of Treatment | 90.67 percentage change in HAE attacks/month | Standard Deviation 22.433 |
| CSL312 | Percentage Change in the Time-normalized Number of HAE Attacks Per Month During the Treatment Period Compared to the Run-in Period | First 3-months of Treatment | 91.10 percentage change in HAE attacks/month | Standard Deviation 21.255 |
| CSL312 | Percentage Change in the Time-normalized Number of HAE Attacks Per Month During the Treatment Period Compared to the Run-in Period | Second 3-months of Treatment | 90.12 percentage change in HAE attacks/month | Standard Deviation 25.624 |
| Placebo | Percentage Change in the Time-normalized Number of HAE Attacks Per Month During the Treatment Period Compared to the Run-in Period | 6 Months of Treatment | 20.21 percentage change in HAE attacks/month | Standard Deviation 42.661 |
| Placebo | Percentage Change in the Time-normalized Number of HAE Attacks Per Month During the Treatment Period Compared to the Run-in Period | First 3-months of Treatment | 18.89 percentage change in HAE attacks/month | Standard Deviation 53.837 |
| Placebo | Percentage Change in the Time-normalized Number of HAE Attacks Per Month During the Treatment Period Compared to the Run-in Period | Second 3-months of Treatment | 29.87 percentage change in HAE attacks/month | Standard Deviation 55.529 |
Comparison: 6 Months of treatmentp-value: <0.001Two-sided Wilcoxon test
Secondary
Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART)
SGART is a self-assessment by the participant and measures the subject's overall treatment response to the investigational product using the following ratings: 0 (none: worse or no response at all, not acceptable), 1 (poor: very little response, not acceptable), 2 (fair: some response, acceptable but could be better), 3 (good: good response, acceptable), and 4 (excellent: excellent response, as good as can be imagined).
Time frame: Up to 6 months
Population: ITT analysis set included all the randomized participants who provided written informed consent and underwent study screening procedures. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CSL312 | Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) | Excellent | 65.8 percentage of participants |
| CSL312 | Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) | None | 2.6 percentage of participants |
| CSL312 | Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) | Poor | 7.9 percentage of participants |
| CSL312 | Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) | Fair | 7.9 percentage of participants |
| CSL312 | Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) | Good | 15.8 percentage of participants |
| Placebo | Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) | Good | 20.8 percentage of participants |
| Placebo | Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) | Fair | 8.3 percentage of participants |
| Placebo | Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) | None | 41.7 percentage of participants |
| Placebo | Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) | Excellent | 12.5 percentage of participants |
| Placebo | Percentage of Participants With a Response to Subject's Global Assessment of Response to Therapy (SGART) | Poor | 16.7 percentage of participants |
Secondary
Percentage of Participants With at Least One AE, SAE, and AESI
AE is any untoward medical occurrence in a participant administered with an investigational product which does not necessarily have a causal relationship with treatment, can be any unfavorable and unintended sign, symptom, or disease temporally associated with use of an investigational product, whether or not considered related to product. SAE is any untoward medical occurrence that results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, or is a medically significant event. An AESI is an AE of scientific and medical concern specific to sponsor's product or program, for which ongoing monitoring and rapid communication by investigator to sponsor is appropriate.
Time frame: From first dose of study drug up to 3 months after the last injection (approximately 8 months)
Population: Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product. The percentage of participants are rounded off to the single decimal point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CSL312 | Percentage of Participants With at Least One AE, SAE, and AESI | AE | 64.1 percentage of participants |
| CSL312 | Percentage of Participants With at Least One AE, SAE, and AESI | SAE | 2.6 percentage of participants |
| CSL312 | Percentage of Participants With at Least One AE, SAE, and AESI | AESI | 0 percentage of participants |
| Placebo | Percentage of Participants With at Least One AE, SAE, and AESI | AE | 60.0 percentage of participants |
| Placebo | Percentage of Participants With at Least One AE, SAE, and AESI | SAE | 0 percentage of participants |
| Placebo | Percentage of Participants With at Least One AE, SAE, and AESI | AESI | 0 percentage of participants |
Secondary
Percentage of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as TEAEs
Laboratory assessments included: Hematology, biochemistry, urinalysis, and coagulation parameters.
Time frame: From first dose of study drug up to 3 months after the last injection (approximately 8 months)
Population: Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product. The percentage of participants are rounded off to the single decimal point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL312 | Percentage of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as TEAEs | 2.6 percentage of participants |
| Placebo | Percentage of Participants With Clinically Significant Abnormalities in Laboratory Assessments Reported as TEAEs | 8.0 percentage of participants |
Secondary
Percentage of Participants With CSL312-induced Anti-CSL312 Antibodies
Time frame: Up to 6 months
Population: Safety analysis set included all the randomized participants who provided written informed consent, underwent study screening procedures and received at least 1 dose of the investigational product. The percentage of participants are rounded off to the single decimal point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CSL312 | Percentage of Participants With CSL312-induced Anti-CSL312 Antibodies | 2.6 percentage of participants |
| Placebo | Percentage of Participants With CSL312-induced Anti-CSL312 Antibodies | 0 percentage of participants |
Secondary
Relative Difference in Means in the Time-Normalized Number of HAE Attacks Per Month Between CSL312 to Placebo
Relative difference in means in the time-normalized number of HAE attacks per month CSL312 to Placebo was calculated as: 100 \* \[(mean time-normalized number of HAE attacks for CSL312 - mean time-normalized number of HAE attacks for placebo) / mean time-normalized number of HAE attacks for placebo\]. Time-normalized number of HAE attacks per month during treatment was calculated per participant as: \[number of HAE attacks / length of participant treatment in days\] \* 30.4375.
Time frame: 6 months, first 3-months and second 3-months of treatment period
Population: ITT analysis set included all randomized participants who provided written informed consent and underwent study screening procedures. 'Overall number of participants analyzed' indicates number of participants with data available for outcome measure (OM) analysis. 'Number analyzed' indicates number of participants with data available for analysis at specified time point. As pre-specified in protocol and SAP, data for this OM was reported for participants of CSL312 and Placebo Comparison group.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| CSL312 | Relative Difference in Means in the Time-Normalized Number of HAE Attacks Per Month Between CSL312 to Placebo | 6 Months of Treatment | -86.51 number of HAE attacks per month |
| CSL312 | Relative Difference in Means in the Time-Normalized Number of HAE Attacks Per Month Between CSL312 to Placebo | First 3-months of Treatment | -86.64 number of HAE attacks per month |
| CSL312 | Relative Difference in Means in the Time-Normalized Number of HAE Attacks Per Month Between CSL312 to Placebo | Second 3-months of Treatment | -85.01 number of HAE attacks per month |
p-value: <0.001Two-sided Wilcoxon test
Secondary
Time-normalized Number of HAE Attacks Per Month in the First 3-months and Second 3-months of Treatment Period
Time-normalized number of HAE attacks per month during treatment was calculated per participant as: \[number of HAE attacks / length of participant treatment in days\] \* 30.4375.
Time frame: First 3-months and second 3-months of treatment period
Population: ITT analysis set included all the randomized participants who provided written informed consent and underwent study screening procedures. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL312 | Time-normalized Number of HAE Attacks Per Month in the First 3-months and Second 3-months of Treatment Period | First 3-months of Treatment | 0.26 number of HAE attacks per month | Standard Deviation 0.749 |
| CSL312 | Time-normalized Number of HAE Attacks Per Month in the First 3-months and Second 3-months of Treatment Period | Second 3-months of Treatment | 0.28 number of HAE attacks per month | Standard Deviation 0.652 |
| Placebo | Time-normalized Number of HAE Attacks Per Month in the First 3-months and Second 3-months of Treatment Period | First 3-months of Treatment | 1.97 number of HAE attacks per month | Standard Deviation 1.287 |
| Placebo | Time-normalized Number of HAE Attacks Per Month in the First 3-months and Second 3-months of Treatment Period | Second 3-months of Treatment | 1.86 number of HAE attacks per month | Standard Deviation 1.603 |
Comparison: First 3-months of treatmentp-value: <0.001Two-sided Wilcoxon test
Comparison: Second 3-months of treatmentp-value: <0.001Two-sided Wilcoxon test
Secondary
Time-Normalized Number of HAE Attacks Per Month Requiring On-Demand Treatment
Time-normalized number of HAE attacks per month requiring on-demand treatment was calculated per participant as: \[number of HAE attacks requiring on-demand treatment / length of participant in days\] \* 30.4375.
Time frame: 6 months, first 3-months and second 3-months of treatment period
Population: ITT analysis set included all the randomized participants who provided written informed consent and underwent study screening procedures. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL312 | Time-Normalized Number of HAE Attacks Per Month Requiring On-Demand Treatment | 6 Months of Treatment | 0.23 number of HAE attacks per month | Standard Deviation 0.663 |
| CSL312 | Time-Normalized Number of HAE Attacks Per Month Requiring On-Demand Treatment | First 3-months of Treatment | 0.24 number of HAE attacks per month | Standard Deviation 0.748 |
| CSL312 | Time-Normalized Number of HAE Attacks Per Month Requiring On-Demand Treatment | Second 3-months of Treatment | 0.23 number of HAE attacks per month | Standard Deviation 0.61 |
| Placebo | Time-Normalized Number of HAE Attacks Per Month Requiring On-Demand Treatment | 6 Months of Treatment | 1.86 number of HAE attacks per month | Standard Deviation 1.412 |
| Placebo | Time-Normalized Number of HAE Attacks Per Month Requiring On-Demand Treatment | First 3-months of Treatment | 1.76 number of HAE attacks per month | Standard Deviation 1.378 |
| Placebo | Time-Normalized Number of HAE Attacks Per Month Requiring On-Demand Treatment | Second 3-months of Treatment | 1.80 number of HAE attacks per month | Standard Deviation 1.626 |
Comparison: 6 Months of treatmentp-value: <0.001Two-sided Wilcoxon test
Comparison: First 3-months of treatmentp-value: <0.001Two-sided Wilcoxon test
Comparison: Second 3-months of treatmentp-value: <0.001Two-sided Wilcoxon test
Secondary
Time-Normalized Number of Moderate or Severe HAE Attacks Per Month
Time-normalized number of moderate or severe HAE attacks per month during treatment period was calculated per participant as: \[number of moderate or severe HAE attacks / length of participant treatment in days\] \* 30.4375.
Time frame: 6 months, first 3-months and second 3-months of treatment period
Population: ITT analysis set included all the randomized participants who provided written informed consent and underwent study screening procedures. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants with data available for analysis at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CSL312 | Time-Normalized Number of Moderate or Severe HAE Attacks Per Month | 6 Months of Treatment | 0.13 number of HAE attacks per month | Standard Deviation 0.296 |
| CSL312 | Time-Normalized Number of Moderate or Severe HAE Attacks Per Month | First 3-months of Treatment | 0.12 number of HAE attacks per month | Standard Deviation 0.305 |
| CSL312 | Time-Normalized Number of Moderate or Severe HAE Attacks Per Month | Second 3-months of Treatment | 0.13 number of HAE attacks per month | Standard Deviation 0.32 |
| Placebo | Time-Normalized Number of Moderate or Severe HAE Attacks Per Month | First 3-months of Treatment | 1.25 number of HAE attacks per month | Standard Deviation 1.091 |
| Placebo | Time-Normalized Number of Moderate or Severe HAE Attacks Per Month | 6 Months of Treatment | 1.35 number of HAE attacks per month | Standard Deviation 1.166 |
| Placebo | Time-Normalized Number of Moderate or Severe HAE Attacks Per Month | Second 3-months of Treatment | 1.24 number of HAE attacks per month | Standard Deviation 1.296 |
Comparison: 6 Months of treatmentp-value: <0.001Two-sided Wilcoxon test
Comparison: First 3-months of treatmentp-value: <0.001Two-sided Wilcoxon test
Comparison: Second 3-months of treatmentp-value: <0.001Two-sided Wilcoxon test