Hereditary Angioedema (HAE)Phase 3NCT02865720
Study of C1 Inhibitor (Human) for the Prevention of Angioedema Attacks and Treatment of Breakthrough Attacks in Japanese Subjects With Hereditary Angioedema (HAE)
A Phase 3 study testing CINRYZE 500 U and CINRYZE 1000 U in people with Hereditary Angioedema (HAE), run by Shire at 10 sites in Japan.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Hereditary Angioedema (HAE)
- What is being tested?
- CINRYZE 500 U and CINRYZE 1000 U
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 10 sitesJapan
- Study dates
- 8 Sep 2016to 23 Jun 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
- Subjects 2 to 5 years of age must weigh at least 12.5 kg; and
- Subjects 6 years of age and above must weigh at least 25 kg.
- 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.
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- 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):
- Non-hormonal methods (eg, abstinence, barrier control) for at least 1 complete menstrual cycle before the Screening Visit.
- Stable doses of estrogen and/or progestin containing products for at least 2 months before the Screening Visit.
- 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.
Who cannot join
- Have a history of hypercoagulability (abnormal blood clotting).
- Have a diagnosis of acquired angioedema or be known to have C1 INH antibodies.
- Have a history of allergic reaction to C1 INH products, including CINRYZE (or any of the components of CINRYZE) or other blood products.
- Have received C1 INH therapy or any blood products within 3 days before the first dose of study drug.
- Have had signs or symptoms of an angioedema attack within 2 days before the first dose of study drug.
- Have any change (start, stop, or change in dose) in androgen therapy (eg, danazol, oxandrolone, stanozolol, testosterone), tranexamic acid, epsilon-aminocaproic acid (EACA), or other antifibrinolytics within 14 days before the first dose of study drug.
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- If female, have started taking or changed the dose of any hormonal contraceptive regimen or hormone replacement therapy (eg, estrogen/progestin containing products) within 2 months before the first dose of study drug.
- Be pregnant or breastfeeding.
- Have received an investigational drug other than those required for prevention or treatment of angioedema attacks within 30 days before the first dose of study drug.
- Have, as determined by the Investigator and/or the Sponsor's Medical Monitor, any surgical or medical condition that could interfere with the administration of study drug or interpretation of study results.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Japan10 sites
Adachi kyosai Hospital
Adachi City, Tokyo, 120-0022
Asahi General Hospital
Asahi, Chiba, 289-2511
Hiroshima University Hospital
Hiroshima, 734-8551
Shiman University Hospital
Izumo, Shimane, 693-8501
Kobe University Hospital
Kobe, Hyōgo, 650-0017
Gunma University Hospital
Maebashi, Gunma, 371-8511
Naha City Hospital
Naha, Okinawa, 902-8511
Heart Life Hospital
Nakagusuku, Nakagami, 901-2417
Tomakomai City Hospital
Tomakomai, 053-8567
Toyohashi Municipal Hospital
Toyohashi, Aiti, 441-8570
About this study
Official title: A Phase 3, Open-label, Single-period Study to Evaluate the Safety and Treatment Effect of Intravenous Administration of C1 Inhibitor (Human) for the Prevention of Angioedema Attacks and Treatment of Breakthrough Attacks in Japanese Subjects With Hereditary Angioedema (HAE)
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.
- Conditions
- Hereditary Angioedema (HAE)
- Being tested
- CINRYZE 500 U, CINRYZE 1000 U
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CINRYZE 500 UDrug
IV infusion administered twice weekly
CINRYZE 1000 UDrug
IV infusion administered twice weekly
| Study group | Role | What they receive |
|---|---|---|
| Subjects 2 to 5 years of age | Experimental | 500 U of CINRYZE will be administered by IV infusion twice weekly for 12 weeks Receives: Drug: CINRYZE 500 U |
| Subjects 6 years of age and older | Experimental | 1000 U of CINRYZE will be administered by IV infusion twice weekly for 12 weeks. Receives: Drug: CINRYZE 1000 U |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Baseline up to Week 12
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline up to Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2016 (estimated)
- Study start8 Sep 2016
- Primary completion23 Jun 2017
- Study completion23 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hereditary Angioedema (HAE)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02865720
- Sponsor's protocol ID
- SHP616-209
- Other IDs
- 0624-209
- Status last verified
- May 2021
- First submitted
- 9 Aug 2016
- Last updated
- 2 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Open-label, Single-period Study to Evaluate the Safety and Treatment Effect of Intravenous Administration of C1 Inhibitor (Human) for the Prevention of Angioedema Attacks and Treatment of Breakthrough Attacks in Japanese Subjects With Hereditary Angioedema (HAE)
- ClinicalTrials.gov ID
- NCT02865720
- Acronym / sponsor ID
- SHP616-209
- Conditions
- Hereditary Angioedema (HAE)
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 8 Sep 2016 (actual)
- Primary completion
- 23 Jun 2017 (actual)
- Study completion
- 23 Jun 2017 (actual)
- First posted
- 12 Aug 2016 (estimated)
- Results
- Posted 31 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Subjects 2 to 5 years of age | Experimental | Drug: CINRYZE 500 U500 U of CINRYZE will be administered by IV infusion twice weekly for 12 weeks |
| Subjects 6 years of age and older | Experimental | Drug: CINRYZE 1000 U1000 U of CINRYZE will be administered by IV infusion twice weekly for 12 weeks. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (10 listed)
- Have a history of hypercoagulability (abnormal blood clotting).
- Have a diagnosis of acquired angioedema or be known to have C1 INH antibodies.
- Have a history of allergic reaction to C1 INH products, including CINRYZE (or any of the components of CINRYZE) or other blood products.
- Have received C1 INH therapy or any blood products within 3 days before the first dose of study drug.
- Have had signs or symptoms of an angioedema attack within 2 days before the first dose of study drug.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CINRYZE 500 UIV infusion administered twice weekly | Drug | Subjects 2 to 5 years of age |
| CINRYZE 1000 UIV infusion administered twice weekly | Drug | Subjects 6 years of age and older |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From start of study drug administration up to Week 12
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.
Number of Participants With Clinically Significant Abnormalities in Physical Examination Reported as Adverse Events (AEs)
Time frame: From start of study drug administration up to Week 12
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.
Number of Participants With Potentially Clinically Important (PCI) Vital Signs Reported as Adverse Events (AEs)
Time frame: Baseline up to Week 12
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.
Number of Participants With Potentially Clinically Important (PCI) Clinical Laboratory Assessments Reported as Adverse Events (AEs)
Time frame: Baseline up to Week 12
Number of participants with potentially clinically important (PCI) clinical laboratory assessments reported as adverse events were reported.
Concentration of C1 Esterase Inhibitor (C1 INH) Antigen (Protein Volume) at Week 1
Time frame: Week 1: Pre-dose, 0.5, 1, 2, 6, 24, 48, 72 and 96 hours (h) post-dose
C1 INH antigen concentration in plasma was determined using an automated nephelometric assay.
Concentration of C1 Esterase Inhibitor (C1 INH) Antigen (Protein Volume) at Week 12
Time frame: Week 12: Pre-dose, 0.5, 1, 2, 6, 24, 48, 72 and 96 h post-dose
C1 INH antigen concentration in plasma was determined using an automated nephelometric assay.
Concentration of Plasma Complement C4 at Week 1
Time frame: Week 1: Pre-dose, 0.5, 1, 2, 6, 24, 48, 72 and 96 h post-dose
Concentration of plasma complement C4 was reported.
Concentration of Plasma Complement C4 at Week 12
Time frame: Week 12: Pre-dose, 0.5, 1, 2, 6, 24, 48, 72 and 96 h post-dose
Concentration of plasma complement C4 was reported.
Concentration of Plasma Complement C1q at Week 1
Time frame: Baseline (Week 1)
Concentration of plasma complement C1q was reported.
Normalized Number of Angioedema Attacks (NNA) Per Month
Time frame: Baseline up to Week 12
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).
Number of Participants With Angioedema Attacks in Different Anatomic Locations
Time frame: Baseline up to Week 12
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.
Average Severity (Intensity) of Angioedema Attacks
Time frame: Baseline up to Week 12
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).
Average Duration of Angioedema Attacks
Time frame: Baseline up to Week 12
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.
Normalized Number of Angioedema Attacks (NNA) Per Month Treated With Rescue Medication
Time frame: Baseline up to Week 12
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.
Number of Participants Achieving Clinical Responder Rate Relative to Historical Data
Time frame: Baseline up to Week 12
Number of participants achieving at least 50 percent (%), 70% or 90% reduction in NNA relative to NNA for historical data was reported.
Change From Baseline in Angioedema Quality of Life (AE-QoL) in Treatment Period
Time frame: Baseline, Week 12
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.
Number of Participants With Breakthrough Angioedema Attacks
Time frame: Baseline up to Week 12
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.
Time From Attack Onset to Initial Improvement and Complete Resolution
Time frame: Baseline up to Week 12
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.
Time From Onset of Attack to Time Treated by CINRYZE
Time frame: Baseline up to Week 12
The median time from onset of attack to time treated with CINRYZE was reported.
Time From Treatment With CINRYZE to Initial Improvement
Time frame: Baseline up to Week 12
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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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Active, not recruitingPhase 3
HAELO: A Phase 3 Study to Evaluate NTLA-2002 in Participants With Hereditary Angioedema (HAE)
Hereditary Angioedema
RecruitingPhase 3
Study of IV Human Plasma-derived C1 Esterase Inhibitor Concentrate in Patients With Congenital C1-INH Deficiency for Treatment and Pre-procedure Preventing of Acute Hereditary Angioedema Attacks
Acute Hereditary Angio Edema
Active, not recruitingPhase 1/2
NTLA-2002 in Adults With Hereditary Angioedema (HAE)
Hereditary Angioedema
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CINRYZE 500 U and CINRYZE 1000 U in people with Hereditary Angioedema (HAE), run by Shire at 10 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: From start of study drug administration up to Week 12). The study lists 20 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2021.