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| ID | Type | Description | Link |
|---|---|---|---|
| 0624-209 | Other Identifier | Shire |
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The purpose of this study is to determine if an investigational treatment is safe and well tolerated when administered by intravenous (IV) infusion in Japanese subjects with HAE.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Subjects 2 to 5 years of age | Experimental | 500 U of CINRYZE will be administered by IV infusion twice weekly for 12 weeks |
|
| Subjects 6 years of age and older | Experimental | 1000 U of CINRYZE will be administered by IV infusion twice weekly for 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CINRYZE 500 U | Drug | IV infusion administered twice weekly |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered an investigational product and that did not necessarily have a causal relationship with the treatment. TEAEs were defined as all AEs that started during the treatment period and up to 7 days after the last dose of investigational product, or AEs that were seen at baseline but worsened in frequency and/or severity during the treatment period and up to 7 days after the last dose of investigational product. | From start of study drug administration up to Week 12 |
| Number of Participants With Clinically Significant Abnormalities in Physical Examination Reported as Adverse Events (AEs) | Physical examinations included measurement of body weight and height. Clinically significant abnormalities related to physical examination as determined by investigator were recorded and reported as AE. | From start of study drug administration up to Week 12 |
| Number of Participants With Potentially Clinically Important (PCI) Vital Signs Reported as Adverse Events (AEs) | Vital sign assessments included systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate. Investigator used both absolute values and change from baseline values to determine if the vital sign was potentially clinically important. Criteria for the potential clinical importance of both absolute and change from baseline values were pre-specified as: SBP (less than [<] 90 millimeter of mercury [mmHg]; greater than or equal to [>=] 140 mmHg), DBP (< 60 mmHg; >=90 mmHg) and pulse (less than or equal to [<=] 50 beats per minute [bpm]; >= 100 bpm. A participant's vital sign had to meet both the absolute and change from baseline criteria to be considered as potentially clinically important. | Baseline up to Week 12 |
| Number of Participants With Potentially Clinically Important (PCI) Clinical Laboratory Assessments Reported as Adverse Events (AEs) |
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Inclusion Criteria:
Be of Japanese descent, defined as born in Japan and having Japanese parents and Japanese maternal and paternal grandparents.
Be ≥2 years of age.
Meet the following minimum body weight criteria:
Have a confirmed diagnosis of Type I or Type II HAE. NOTE: Diagnosis may be based on historical data including family history, clinical symptoms (characteristic attacks), or documentation of low level of C1 INH protein and/or C1 INH activity.
Have a history of at least one angioedema attack per month (on average) during the 3 consecutive months immediately before enrollment.
Agree to adhere to the protocol-defined schedule of assessments and procedures.
Agree to avoid his/her known angioedema attack triggers during the study to the best of his/her ability.
If a female of reproductive age, be postmenopausal (≥12 months following cessation of menstruation), surgically sterile, or following an acceptable method of birth control (and agree to continue its use through 1 month after the last dose of study drug):
If a male of reproductive age, be surgically sterile or agree to follow an acceptable method of birth control (eg, abstinence, barrier control) from the Screening Visit through 2 months after the last dose of study drug.
If an adult, be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.
OR If a child or minor (<20 years of age), have a parent/legal guardian who is informed of the nature of the study provide written informed consent (ie, permission) for the child to participate in the study before any study-specific procedures are performed. Assent will be obtained from children ≥14 years of age.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Toyohashi Municipal Hospital | Toyohashi | Aiti | 441-8570 | Japan | ||
| Asahi General Hospital |
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
A total of 8 participants were screened and enrolled. Investigational product administrations were planned according to participants' age; 500 units (U) for participants 2 to 5 years and 1000 U for participants 6 years and older. However, as no participants under the age of 6 years were enrolled, only the higher dose of 1000 U was administered.
The study was conducted in 9 study centers in Japan between 13 Sep 2016 (First participant first visit) and 23 June 2017 (Last participant last visit).
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| ID | Title | Description |
|---|---|---|
| FG000 | CINRYZE 500 U | Participants received 500 U CINRYZE intravenous (IV) injection twice weekly for 12 weeks. |
| FG001 | CINRYZE 1000 U | Participants received 1000 U CINRYZE IV injection twice weekly for 12 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 30, 2016 | Jun 20, 2018 |
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| CINRYZE 1000 U |
| Drug |
IV infusion administered twice weekly |
|
Number of participants with potentially clinically important (PCI) clinical laboratory assessments reported as adverse events were reported.
| Baseline up to Week 12 |
| Concentration of C1 Esterase Inhibitor (C1 INH) Antigen (Protein Volume) at Week 1 | C1 INH antigen concentration in plasma was determined using an automated nephelometric assay. | Week 1: Pre-dose, 0.5, 1, 2, 6, 24, 48, 72 and 96 hours (h) post-dose |
| Concentration of C1 Esterase Inhibitor (C1 INH) Antigen (Protein Volume) at Week 12 | C1 INH antigen concentration in plasma was determined using an automated nephelometric assay. | Week 12: Pre-dose, 0.5, 1, 2, 6, 24, 48, 72 and 96 h post-dose |
| Concentration of Plasma Complement C4 at Week 1 | Concentration of plasma complement C4 was reported. | Week 1: Pre-dose, 0.5, 1, 2, 6, 24, 48, 72 and 96 h post-dose |
| Concentration of Plasma Complement C4 at Week 12 | Concentration of plasma complement C4 was reported. | Week 12: Pre-dose, 0.5, 1, 2, 6, 24, 48, 72 and 96 h post-dose |
| Concentration of Plasma Complement C1q at Week 1 | Concentration of plasma complement C1q was reported. | Baseline (Week 1) |
| Normalized Number of Angioedema Attacks (NNA) Per Month | Angioedema attack was defined as any participant-reported (or caregiver-reported) indication of swelling or pain at any location following a report of no swelling or pain on the previous day (that is, there must have been a full symptom-free calendar day preceding the onset of symptoms for an attack to be considered a new attack). NNA was calculated as the overall number of angioedema attacks recorded during the period divided by the number of days in the period and multiplied by 30.4.Number of attacks was normalized for the number of days participants participated in a given period and expressed as the monthly frequency as compared to the historical data where, NNA was the number of angioedema attacks during 3 months prior to study drug administration. Historical data was obtained from medical or angioedema history electronic case report forms (eCRF). | Baseline up to Week 12 |
| Number of Participants With Angioedema Attacks in Different Anatomic Locations | Anatomic locations where there was a presence of pain or swelling of any level of severity; mild, moderate or severe at any day during the attack were reported. Mild: the attack symptoms were noticeable but were easily tolerated by the participant and did not interfere with the participant's daily activities. Moderate: the attack symptoms interfered with the participant's ability to attend work/school or participate in family life and social/recreational activities and severe: the attack symptoms significantly limited the participant's ability to attend work/school or participate in family life and social/recreational activities. Number of participants with angioedema attacks in different anatomic locations in treatment period was compared to NNA for historical data. Historical data was based on the typical location of angioedema attacks in the 3 months prior to study drug administration. Here, H refers to historical and T refers to treatment. | Baseline up to Week 12 |
| Average Severity (Intensity) of Angioedema Attacks | All attacks in each therapy period were assigned a value of 1 (mild), 2 (moderate), or 3 (severe). Attack severity was considered the highest value assigned by the participant to any swelling location on any day during the attack. The average severity was derived by dividing the cumulative severity score by the total number of attacks. Average severity was set to 0 if there was no attack in a period. Average severity of angioedema attacks in treatment period compared to the NNA of angioedema attacks for historical data was reported. Historical data was based on the typical severity of angioedema attacks in the 3 months prior to study drug administration. Historical data was obtained from medical or angioedema history electronic case report forms (eCRF). | Baseline up to Week 12 |
| Average Duration of Angioedema Attacks | Average duration of attacks was calculated by dividing the cumulative duration of attacks by the total number of attacks during the treatment period. Historical data was based on the typical severity of angioedema attacks in the 3 months prior to study drug administration. Average duration of angioedema attacks in treatment period was compared to the NNA for historical data. Historical data was obtained from medical or angioedema history eCRF. | Baseline up to Week 12 |
| Normalized Number of Angioedema Attacks (NNA) Per Month Treated With Rescue Medication | The normalized number of angioedema attacks was calculated as the overall number of angioedema attacks recorded during the period divided by the number of days in the period and multiplied by 30.4. NNA treated with rescue medications were reported for CINRYZE, non-CINRYZE C1-INH or not treated with C1-INH (including attacks treated with any medications other than C1-INH or untreated attacks). CINRYZE was only considered as a rescue medication when treated for breakthrough attack treatment. For historical data, only medications taken prior to the start of drug study drug administration and had an indication of "hereditary angioedema (HAE) management - acute treatment" selected on the prior and concomitant medications and therapy were considered as rescue medications. Historical data was obtained from medical or angioedema history eCRF. | Baseline up to Week 12 |
| Number of Participants Achieving Clinical Responder Rate Relative to Historical Data | Number of participants achieving at least 50 percent (%), 70% or 90% reduction in NNA relative to NNA for historical data was reported. | Baseline up to Week 12 |
| Change From Baseline in Angioedema Quality of Life (AE-QoL) in Treatment Period | Angioedema quality of life (AE-QoL) questionnaire was a self-administered validated angioedema disease-specific quality of life instrument. It consisted of 17 specific questions that were associated with work, physical activity, free time, social relations, and diet. Each of the 17 items had a 5-point response scale ranging from 1 (Never) to 5 (Very Often). The questionnaire was scored according to the developers' guidelines to produce a total score and 4 domain scores (functioning, fatigue/mood, fear/shame, nutrition). Raw domain scores (mean of the item scores within each scale) and the raw total score (mean of all item scores) were rescaled using linear transformations into final percentage scores ranging 0 to 100, based on the maximum possible score, where the higher the score the greater the QoL impairment. | Baseline, Week 12 |
| Number of Participants With Breakthrough Angioedema Attacks | A breakthrough attack was defined as an angioedema attack that occurs during long-term prevention therapy with CINRYZE (that is, between first study drug and last study drug dose). Number of participants with 1, 2, 3 or more angioedema attacks and who achieved initial improvement and complete resolution were also reported. Breakthrough angioedema attacks assessed by CINRYZE treatment, non-CINRYZE C1 INH treatment and untreated with C1-INH were reported. Here BAA refers to breakthrough angioedema attacks. | Baseline up to Week 12 |
| Time From Attack Onset to Initial Improvement and Complete Resolution | Time to initial improvement (TII) was calculated from the time of study drug administration to initial symptom improvement. Time to complete resolution was defined as the time from the onset of attack to complete resolution of all symptoms. Time to initial improvement and time to complete resolution as assessed by CINRYZE, non-CINRYZE and untreated were reported. | Baseline up to Week 12 |
| Time From Onset of Attack to Time Treated by CINRYZE | The median time from onset of attack to time treated with CINRYZE was reported. | Baseline up to Week 12 |
| Time From Treatment With CINRYZE to Initial Improvement | Time to initial improvement was calculated from the time of study drug administration to initial symptom improvement. Median time from treatment with CINRYZE to initial improvement was reported. | Baseline up to Week 12 |
| Asahi |
| Chiba |
| 289-2511 |
| Japan |
| Gunma University Hospital | Maebashi | Gunma | 371-8511 | Japan |
| Kobe University Hospital | Kobe | Hyōgo | 650-0017 | Japan |
| Heart Life Hospital | Nakagusuku | Nakagami | 901-2417 | Japan |
| Naha City Hospital | Naha | Okinawa | 902-8511 | Japan |
| Shiman University Hospital | Izumo | Shimane | 693-8501 | Japan |
| Adachi kyosai Hospital | Adachi City | Tokyo | 120-0022 | Japan |
| Hiroshima University Hospital | Hiroshima | 734-8551 | Japan |
| Tomakomai City Hospital | Tomakomai | 053-8567 | Japan |
| COMPLETED |
|
| NOT COMPLETED |
|
Intent-to-treat safety (ITT-S) set included participants who received any amount of investigational product.
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| ID | Title | Description |
|---|---|---|
| BG000 | CINRYZE 500 U | Participants received 500 U CINRYZE IV injection twice weekly for 12 weeks. |
| BG001 | CINRYZE 1000 U | Participants received 1000 U CINRYZE IV injection twice weekly for 12 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | year |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered an investigational product and that did not necessarily have a causal relationship with the treatment. TEAEs were defined as all AEs that started during the treatment period and up to 7 days after the last dose of investigational product, or AEs that were seen at baseline but worsened in frequency and/or severity during the treatment period and up to 7 days after the last dose of investigational product. | ITT-S set included participants who received any amount of investigational product. | Posted | Count of Participants | Participants | From start of study drug administration up to Week 12 |
|
|
| ||||||||||||||||||||||||||
| Primary | Number of Participants With Clinically Significant Abnormalities in Physical Examination Reported as Adverse Events (AEs) | Physical examinations included measurement of body weight and height. Clinically significant abnormalities related to physical examination as determined by investigator were recorded and reported as AE. | ITT-S set included participants who received any amount of investigational product. | Posted | Count of Participants | Participants | From start of study drug administration up to Week 12 |
|
| |||||||||||||||||||||||||||
| Primary | Number of Participants With Potentially Clinically Important (PCI) Vital Signs Reported as Adverse Events (AEs) | Vital sign assessments included systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate. Investigator used both absolute values and change from baseline values to determine if the vital sign was potentially clinically important. Criteria for the potential clinical importance of both absolute and change from baseline values were pre-specified as: SBP (less than [<] 90 millimeter of mercury [mmHg]; greater than or equal to [>=] 140 mmHg), DBP (< 60 mmHg; >=90 mmHg) and pulse (less than or equal to [<=] 50 beats per minute [bpm]; >= 100 bpm. A participant's vital sign had to meet both the absolute and change from baseline criteria to be considered as potentially clinically important. | ITT-S set included participants who received any amount of investigational product. | Posted | Count of Participants | Participants | Baseline up to Week 12 |
|
| |||||||||||||||||||||||||||
| Primary | Number of Participants With Potentially Clinically Important (PCI) Clinical Laboratory Assessments Reported as Adverse Events (AEs) | Number of participants with potentially clinically important (PCI) clinical laboratory assessments reported as adverse events were reported. | ITT-S set included participants who received any amount of investigational product. | Posted | Count of Participants | Participants | Baseline up to Week 12 |
|
| |||||||||||||||||||||||||||
| Primary | Concentration of C1 Esterase Inhibitor (C1 INH) Antigen (Protein Volume) at Week 1 | C1 INH antigen concentration in plasma was determined using an automated nephelometric assay. | Pharmacokinetic (PK) set included all participants with evaluable PK profiles. | Posted | Mean | Standard Deviation | Gram per liter (g/L) | Week 1: Pre-dose, 0.5, 1, 2, 6, 24, 48, 72 and 96 hours (h) post-dose |
|
| ||||||||||||||||||||||||||
| Primary | Concentration of C1 Esterase Inhibitor (C1 INH) Antigen (Protein Volume) at Week 12 | C1 INH antigen concentration in plasma was determined using an automated nephelometric assay. | PK set included all participants with evaluable PK profiles. | Posted | Mean | Standard Deviation | gram per liter (g/L) | Week 12: Pre-dose, 0.5, 1, 2, 6, 24, 48, 72 and 96 h post-dose |
|
| ||||||||||||||||||||||||||
| Primary | Concentration of Plasma Complement C4 at Week 1 | Concentration of plasma complement C4 was reported. | Pharmacodynamic (PD) set included all participants with evaluable PD profiles. | Posted | Mean | Standard Deviation | Milligram per liter (mg/L) | Week 1: Pre-dose, 0.5, 1, 2, 6, 24, 48, 72 and 96 h post-dose |
|
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| Primary | Concentration of Plasma Complement C4 at Week 12 | Concentration of plasma complement C4 was reported. | PD set included all participants with evaluable PD profiles. | Posted | Mean | Standard Deviation | mg/L | Week 12: Pre-dose, 0.5, 1, 2, 6, 24, 48, 72 and 96 h post-dose |
|
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| Primary | Concentration of Plasma Complement C1q at Week 1 | Concentration of plasma complement C1q was reported. | PD set included all participants with evaluable PD profiles. | Posted | Mean | Standard Deviation | International units per milliliter | Baseline (Week 1) |
|
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| Primary | Normalized Number of Angioedema Attacks (NNA) Per Month | Angioedema attack was defined as any participant-reported (or caregiver-reported) indication of swelling or pain at any location following a report of no swelling or pain on the previous day (that is, there must have been a full symptom-free calendar day preceding the onset of symptoms for an attack to be considered a new attack). NNA was calculated as the overall number of angioedema attacks recorded during the period divided by the number of days in the period and multiplied by 30.4.Number of attacks was normalized for the number of days participants participated in a given period and expressed as the monthly frequency as compared to the historical data where, NNA was the number of angioedema attacks during 3 months prior to study drug administration. Historical data was obtained from medical or angioedema history electronic case report forms (eCRF). | Full analysis set (FAS) included all participants who had at least 1 post-baseline efficacy assessment. | Posted | Mean | Standard Deviation | Angioedema attacks per month | Baseline up to Week 12 |
|
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| Primary | Number of Participants With Angioedema Attacks in Different Anatomic Locations | Anatomic locations where there was a presence of pain or swelling of any level of severity; mild, moderate or severe at any day during the attack were reported. Mild: the attack symptoms were noticeable but were easily tolerated by the participant and did not interfere with the participant's daily activities. Moderate: the attack symptoms interfered with the participant's ability to attend work/school or participate in family life and social/recreational activities and severe: the attack symptoms significantly limited the participant's ability to attend work/school or participate in family life and social/recreational activities. Number of participants with angioedema attacks in different anatomic locations in treatment period was compared to NNA for historical data. Historical data was based on the typical location of angioedema attacks in the 3 months prior to study drug administration. Here, H refers to historical and T refers to treatment. | FAS included all participants who had at least 1 post-baseline efficacy assessment. | Posted | Count of Participants | Participants | Baseline up to Week 12 |
|
| |||||||||||||||||||||||||||
| Primary | Average Severity (Intensity) of Angioedema Attacks | All attacks in each therapy period were assigned a value of 1 (mild), 2 (moderate), or 3 (severe). Attack severity was considered the highest value assigned by the participant to any swelling location on any day during the attack. The average severity was derived by dividing the cumulative severity score by the total number of attacks. Average severity was set to 0 if there was no attack in a period. Average severity of angioedema attacks in treatment period compared to the NNA of angioedema attacks for historical data was reported. Historical data was based on the typical severity of angioedema attacks in the 3 months prior to study drug administration. Historical data was obtained from medical or angioedema history electronic case report forms (eCRF). | FAS included all participants who had at least 1 postbaseline efficacy assessment. | Posted | Mean | Standard Deviation | Units on a scale | Baseline up to Week 12 |
|
| ||||||||||||||||||||||||||
| Primary | Average Duration of Angioedema Attacks | Average duration of attacks was calculated by dividing the cumulative duration of attacks by the total number of attacks during the treatment period. Historical data was based on the typical severity of angioedema attacks in the 3 months prior to study drug administration. Average duration of angioedema attacks in treatment period was compared to the NNA for historical data. Historical data was obtained from medical or angioedema history eCRF. | FAS included all participants who had at least 1 post-baseline efficacy assessment. | Posted | Mean | Standard Deviation | Days | Baseline up to Week 12 |
|
| ||||||||||||||||||||||||||
| Primary | Normalized Number of Angioedema Attacks (NNA) Per Month Treated With Rescue Medication | The normalized number of angioedema attacks was calculated as the overall number of angioedema attacks recorded during the period divided by the number of days in the period and multiplied by 30.4. NNA treated with rescue medications were reported for CINRYZE, non-CINRYZE C1-INH or not treated with C1-INH (including attacks treated with any medications other than C1-INH or untreated attacks). CINRYZE was only considered as a rescue medication when treated for breakthrough attack treatment. For historical data, only medications taken prior to the start of drug study drug administration and had an indication of "hereditary angioedema (HAE) management - acute treatment" selected on the prior and concomitant medications and therapy were considered as rescue medications. Historical data was obtained from medical or angioedema history eCRF. | FAS included all participants who had at least 1 post-baseline efficacy assessment. | Posted | Mean | Standard Deviation | Angioedema attacks per month | Baseline up to Week 12 |
|
| ||||||||||||||||||||||||||
| Primary | Number of Participants Achieving Clinical Responder Rate Relative to Historical Data | Number of participants achieving at least 50 percent (%), 70% or 90% reduction in NNA relative to NNA for historical data was reported. | FAS included all participants who had at least 1 post-baseline efficacy assessment. | Posted | Count of Participants | Participants | Baseline up to Week 12 |
|
| |||||||||||||||||||||||||||
| Primary | Change From Baseline in Angioedema Quality of Life (AE-QoL) in Treatment Period | Angioedema quality of life (AE-QoL) questionnaire was a self-administered validated angioedema disease-specific quality of life instrument. It consisted of 17 specific questions that were associated with work, physical activity, free time, social relations, and diet. Each of the 17 items had a 5-point response scale ranging from 1 (Never) to 5 (Very Often). The questionnaire was scored according to the developers' guidelines to produce a total score and 4 domain scores (functioning, fatigue/mood, fear/shame, nutrition). Raw domain scores (mean of the item scores within each scale) and the raw total score (mean of all item scores) were rescaled using linear transformations into final percentage scores ranging 0 to 100, based on the maximum possible score, where the higher the score the greater the QoL impairment. | FAS included all participants who had at least 1 post-baseline efficacy assessment. | Posted | Mean | Standard Deviation | Score on a scale | Baseline, Week 12 |
|
| ||||||||||||||||||||||||||
| Primary | Number of Participants With Breakthrough Angioedema Attacks | A breakthrough attack was defined as an angioedema attack that occurs during long-term prevention therapy with CINRYZE (that is, between first study drug and last study drug dose). Number of participants with 1, 2, 3 or more angioedema attacks and who achieved initial improvement and complete resolution were also reported. Breakthrough angioedema attacks assessed by CINRYZE treatment, non-CINRYZE C1 INH treatment and untreated with C1-INH were reported. Here BAA refers to breakthrough angioedema attacks. | FAS included all participants who had at least 1 post-baseline efficacy assessment. Number of participants evaluable for this outcome measure was reported. | Posted | Count of Participants | Participants | Baseline up to Week 12 |
|
| |||||||||||||||||||||||||||
| Primary | Time From Attack Onset to Initial Improvement and Complete Resolution | Time to initial improvement (TII) was calculated from the time of study drug administration to initial symptom improvement. Time to complete resolution was defined as the time from the onset of attack to complete resolution of all symptoms. Time to initial improvement and time to complete resolution as assessed by CINRYZE, non-CINRYZE and untreated were reported. | FAS included all participants who had at least 1 post-baseline efficacy assessment. Number of participants evaluable for this outcome were reported. | Posted | Median | 95% Confidence Interval | Hours | Baseline up to Week 12 |
|
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| Primary | Time From Onset of Attack to Time Treated by CINRYZE | The median time from onset of attack to time treated with CINRYZE was reported. | FAS included all participants who had at least 1 postbaseline efficacy assessment. | Posted | Median | 95% Confidence Interval | Hours | Baseline up to Week 12 |
|
| ||||||||||||||||||||||||||
| Primary | Time From Treatment With CINRYZE to Initial Improvement | Time to initial improvement was calculated from the time of study drug administration to initial symptom improvement. Median time from treatment with CINRYZE to initial improvement was reported. | FAS included all participants who had at least 1 post-baseline efficacy assessment. | Posted | Median | 95% Confidence Interval | Hours | Baseline up to Week 12 |
|
|
From start of study drug administration up to Week 12
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | CINRYZE 1000 U | Participants received 1000 U CINRYZE IV injection twice weekly for 12 weeks. | 0 | 8 | 2 | 8 | 7 | 8 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hereditary angioedema | Congenital, familial and genetic disorders | MedDRA 19.0 | Non-systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA 19.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Non-systematic Assessment |
| |
| Intervertebral disc disorder | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 19.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 19.0 | Non-systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 19.0 | Non-systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA 19.0 | Non-systematic Assessment |
| |
| Seasonal allergy | Immune system disorders | MedDRA 19.0 | Non-systematic Assessment |
| |
| Herpes virus infection | Infections and infestations | MedDRA 19.0 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 19.0 | Non-systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 19.0 | Non-systematic Assessment |
| |
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 19.0 | Non-systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 19.0 | Non-systematic Assessment |
| |
| Cervicobrachial syndrome | Nervous system disorders | MedDRA 19.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 19.0 | Non-systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 19.0 | Non-systematic Assessment |
| |
| Device failure | Product Issues | MedDRA 19.0 | Non-systematic Assessment |
| |
| Breast disorder | Reproductive system and breast disorders | MedDRA 19.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Non-systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 19.0 | Non-systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 21, 2017 | Jun 20, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D054179 | Angioedemas, Hereditary |
| ID | Term |
|---|---|
| D000799 | Angioedema |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000081208 | Hereditary Complement Deficiency Diseases |
| D000081207 | Primary Immunodeficiency Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D007153 | Immunologic Deficiency Syndromes |
Not provided
Not provided
| ID | Term |
|---|---|
| C469952 | SERPING1 protein, human |
Not provided
Not provided
Not provided
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| Pre-dose |
|
| ||||
| 0.5 h post-dose |
|
| ||||
| 1 h post-dose |
|
| ||||
| 2 h post-dose |
|
| ||||
| 6 h post-dose |
|
| ||||
| 24 h post-dose |
|
| ||||
| 48 h post-dose |
|
| ||||
| 72 h post-dose |
|
| ||||
| 96 h post-dose |
|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| Pre-dose |
|
| ||||
| 0.5 h post-dose |
|
| ||||
| 1 h post-dose |
|
| ||||
| 2 h post-dose |
|
| ||||
| 6 h post-dose |
|
| ||||
| 24 h post-dose |
|
| ||||
| 48 h post-dose |
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| ||||
| 72 h post-dose |
|
| ||||
| 96 h post-dose |
|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| Pre-dose |
|
| ||||
| 0.5 h post-dose |
|
| ||||
| 1 h post-dose |
|
| ||||
| 2 h post-dose |
|
| ||||
| 6 h post-dose |
|
| ||||
| 24 h post-dose |
|
| ||||
| 48 h post-dose |
|
| ||||
| 72 h post-dose |
|
| ||||
| 96 h post-dose |
|
|
| Title | Denominators | Categories |
|---|
| Pre-dose |
|
| ||||
| 0.5 h post-dose |
|
| ||||
| 1 h post-dose |
|
| ||||
| 2 h post-dose |
|
| ||||
| 6 h post-dose |
|
| ||||
| 24 h post-dose |
|
| ||||
| 48 h post-dose |
|
| ||||
| 72 h post-dose |
|
| ||||
| 96 h post-dose |
|
|
| Title | Denominators | Categories |
|---|
|
|
|
|
|
|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
| Achieving >= 50% reduction in NNA |
| |||||
| Achieving >= 70% reduction in NNA |
| |||||
| Achieving >= 90% reduction in NNA |
|
|
|
|
| Title | Denominators | Categories | ||||
|---|---|---|---|---|---|---|
|
|