Hereditary AngioedemaPhase 4NCT00914966
A Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE
A Phase 4 study testing C1 inhibitor (human) [C1 INH] in people with Hereditary Angioedema, run by Shire at 11 sites in United States.
Trial summary
The objectives of the study were: 1. To assess the safety and tolerability of escalating doses of CINRYZE. 2. To assess the effect of an escalating dose algorithm for CINRYZE on hereditary angioedema (HAE) attack rates. 3. To assess the immunogenicity of CINRYZE. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Hereditary Angioedema
- What is being tested?
- C1 inhibitor (human) [C1 INH]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 11 sitesUnited States
- Study dates
- 31 Aug 2009to 24 May 2012
- Phase
- Phase 4
- 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 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- To be eligible for this protocol, subjects must:
- Be ≥6 years of age and ≥25 kg body weight.
- Have a confirmed diagnosis of HAE with a documented history of swelling of the face, extremities, gastrointestinal tract, genitalia, or larynx and a history of at least one of the following:
- C1 INH gene mutation
- C4 level below the lower limit of the reference range
- C1 INH antigen level below the lower limit of the reference range
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- Functional C1 INH level below the lower limit of the reference range
- Family history of HAE (i.e., grandparent, parent, sibling)
- Have a history of >1.0 HAE attack per month (average) of any severity during the 3 consecutive months prior to screening while receiving the recommended CINRYZE dosing of 1000 Units every 3 to 4 days via intravenous injection.
- 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, have a parent/legal guardian who is willing and able to provide written informed consent for the child to participate in the study (with assent from the child when appropriate).
Who cannot join
- To be eligible for this protocol, subjects must not:
- 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.
- Have a history of abnormal blood clotting or other coagulopathy.
- Be taking prescription anticoagulant medication.
- Have a history of allergic reaction to CINRYZE or other blood products.
- Have participated in any other investigational drug study within the past 30 days (other than CINRYZE protocols).
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- Have received any blood products (other than CINRYZE) within 60 days prior to screening.
- Have any of the following laboratory values at screening:
- Hemoglobin <8 g/dL
- White blood cell count <2 x 10^9/L or >20 x 10^9/L
- Platelet count <50 x 10^9/L or >400 x 10^9/L
- Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.0 x the upper limit of normal
- Blood urea nitrogen and/or creatinine >2.0 x the upper limit of normal
- Be pregnant or breastfeeding.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Family Allergy and Asthma Center
Atlanta, Georgia, 30342
Study site
Bryan, Texas, 77802
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267
AARA Research Center
Dallas, Texas, 75231
Allergy and Asthma Research Group
Eugene, Oregon, 97401
East Tennessee Center for Clinical Research
Knoxville, Tennessee, 37909
Baker Allergy, Asthma and Dermatology Research Center
Lake Oswego, Oregon, 97035
Winthrop University Hospital
Mineola, New York, 11501
Allergy, Asthma and Immunology Associates
Scottsdale, Arizona, 85251
Marycliff Allergy Specialist
Spokane, Washington, 99204
Institute for Asthma and Allergy
Wheaton, Maryland, 20902
About this study
Official title: A Phase 4 Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE® (C1 Inhibitor [Human]) as Prophylactic Therapy in Subjects With Inadequately Controlled Hereditary Angioedema Attacks
The objectives of the study were:
- To assess the safety and tolerability of escalating doses of CINRYZE.
- To assess the effect of an escalating dose algorithm for CINRYZE on hereditary angioedema (HAE) attack rates.
- To assess the immunogenicity of CINRYZE.
Read the detailed description
Qualifying subjects entered a 3-step dose escalation algorithm:
- Step 1: 1500 Units twice per week (starting dosing regimen for all subjects in the study)
- Step 2: 2000 Units twice per week
- Step 3: 2500 Units twice per week
Each step consisted of 12 weeks of safety monitoring, followed by calculation of average monthly angioedema attack rate based on subject reports of angioedema symptoms (regardless of intensity) and actual duration of therapy for that step.
If a subject was deemed a "success" at a given step and the investigator and medical monitor determined that it was safe for the subject to continue on that dose, the subject entered a 3 month follow-up period at that dose level with continued safety monitoring. The subject could not re-enter the study for purposes of dose escalation during the follow-up period.
If a subject was not deemed a "success," the subject initiated the next highest step of the dose escalation algorithm provided that the investigator and medical monitor agreed that dose escalation was appropriate. If at the end of Step 3 (2500 Units), a subject was not deemed a "success," then the Week 12 visit represented study completion and the subject was referred to the physician who manages their HAE care.
- Conditions
- Hereditary Angioedema
- Being tested
- C1 inhibitor (human) [C1 INH]
- Medical subject headings
- Angioedemas, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C1 inhibitor (human) [C1 INH]Biological
Also called CINRYZE, C1 esterase inhibitor (human)
| Study group | Role | What they receive |
|---|---|---|
| CINRYZE | Experimental | There were 3 potential dose escalation steps:
* Step 1: 1500 Units of CINRYZE (C1 inhibitor [human]) administered by IV infusion twice per week for 12 weeks
* Step 2: 2000 Units of CINRYZE (C1 inhibitor [human]) administered by IV infusion twice per week for 12 weeks
* Step 3: 2500 Units of CINRYZE (C1 inhibitor [human]) administered by IV infusion twice per week for 12 weeks Receives: Biological: C1 inhibitor (human) [C1 INH] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Adverse Events, Hospitalizations, Thrombotic Events, Treatment-emergent C1 INH Antibodies, Post-baseline Toxicity Grade Increases in Clinical Laboratory Parameters, and Post-dose Vital Signs Changes of Potential Clinical Importance
Events reported during the 3 month follow-up period are counted with the dose level at which they occurred.
Measured: 12 to 24 weeks at each dose level
Secondary outcomes (1)
Treatment Effect of Escalating Doses of CINRYZE on HAE Attack Rates
Two definitions of success were applied in this study: 1) Per-protocol success - Average angioedema attack rate of ≤1.0 per month at the end of any dose escalation step (Week 12). The a priori definition of study success was 4 or more subjects with per-protocol success. 2) Investigator-determined success - Based on the investigator's clinical judgment, an average monthly angioedema attack rate demonstrating improvement sufficient for progression to follow-up. In addition, subjects who were not a per-protocol or investigator-determined success, but who experienced a reduction of >1.0 attack per month from their historical angioedema attack rate at the end of any dose escalation step (Week 12), were summarized.
Measured: 12 weeks at each dose level
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2009 (estimated)
- Study start31 Aug 2009
- Primary completion24 May 2012
- Study completion24 May 2012
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 AngioedemaStudies 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 4
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 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
- NCT00914966
- Sponsor's protocol ID
- 0624-400
- Other IDs
- SHP616-400
- Status last verified
- Jun 2021
- First submitted
- 3 Jun 2009
- Last updated
- 23 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 4 Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE® (C1 Inhibitor [Human]) as Prophylactic Therapy in Subjects With Inadequately Controlled Hereditary Angioedema Attacks
- ClinicalTrials.gov ID
- NCT00914966
- Acronym / sponsor ID
- 0624-400
- Conditions
- Hereditary Angioedema
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 31 Aug 2009 (actual)
- Primary completion
- 24 May 2012 (actual)
- Study completion
- 24 May 2012 (actual)
- First posted
- 5 Jun 2009 (estimated)
- Results
- Posted 18 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objectives of the study were:
- To assess the safety and tolerability of escalating doses of CINRYZE.
- To assess the effect of an escalating dose algorithm for CINRYZE on hereditary angioedema (HAE) attack rates.
- To assess the immunogenicity of CINRYZE.
Detailed description
Qualifying subjects entered a 3-step dose escalation algorithm:
- Step 1: 1500 Units twice per week (starting dosing regimen for all subjects in the study)
- Step 2: 2000 Units twice per week
- Step 3: 2500 Units twice per week
Each step consisted of 12 weeks of safety monitoring, followed by calculation of average monthly angioedema attack rate based on subject reports of angioedema symptoms (regardless of intensity) and actual duration of therapy for that step.
If a subject was deemed a "success" at a given step and the investigator and medical monitor determined that it was safe for the subject to continue on that dose, the subject entered a 3 month follow-up period at that dose level with continued safety monitoring. The subject could not re-enter the study for purposes of dose escalation during the follow-up period.
If a subject was not deemed a "success," the subject initiated the next highest step of the dose escalation algorithm provided that the investigator and medical monitor agreed that dose escalation was appropriate. If at the end of Step 3 (2500 Units), a subject was not deemed a "success," then the Week 12 visit represented study completion and the subject was referred to the physician who manages their HAE care.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CINRYZE | Experimental | Biological: C1 inhibitor (human) [C1 INH]There were 3 potential dose escalation steps: * Step 1: 1500 Units of CINRYZE (C1 inhibitor [human]) administered by IV infusion twice per week for 12 weeks * Step 2: 2000 Units of CINRYZE (C1 inhibitor [human]) administered by IV infusion twice per week for 12 weeks * Step 3: 2500 Units of CINRYZE (C1 inhibitor [human]) administered by IV infusion twice per week for 12 weeks |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Be ≥6 years of age and ≥25 kg body weight.
- Have a confirmed diagnosis of HAE with a documented history of swelling of the face, extremities, gastrointestinal tract, genitalia, or larynx and a history of at least one of the following:
- Have a history of >1.0 HAE attack per month (average) of any severity during the 3 consecutive months prior to screening while receiving the recommended CINRYZE dosing of 1000 Units every 3 to 4 days via intravenous injection.
- If an adult, be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.
- OR
Key exclusion criteria (14 listed)
- 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.
- Have a history of abnormal blood clotting or other coagulopathy.
- Be taking prescription anticoagulant medication.
- Have a history of allergic reaction to CINRYZE or other blood products.
- Have participated in any other investigational drug study within the past 30 days (other than CINRYZE protocols).
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 |
|---|---|---|
| C1 inhibitor (human) [C1 INH]Also: CINRYZE, C1 esterase inhibitor (human) | Biological | CINRYZE |
Primary outcome
Number of Subjects With Adverse Events, Hospitalizations, Thrombotic Events, Treatment-emergent C1 INH Antibodies, Post-baseline Toxicity Grade Increases in Clinical Laboratory Parameters, and Post-dose Vital Signs Changes of Potential Clinical Importance
Time frame: 12 to 24 weeks at each dose level
Events reported during the 3 month follow-up period are counted with the dose level at which they occurred.
1 secondary outcome
Treatment Effect of Escalating Doses of CINRYZE on HAE Attack Rates
Time frame: 12 weeks at each dose level
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing C1 inhibitor (human) [C1 INH] in people with Hereditary Angioedema, run by Shire at 11 sites in United States.
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 12 inclusion and 14 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 23 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 11 sites in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 18 Jul 2013). 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 Subjects With Adverse Events, Hospitalizations, Thrombotic Events, Treatment-emergent C1 INH Antibodies, Post-baseline Toxicity Grade Increases in Clinical Laboratory Parameters, and Post-dose Vital Signs Changes of Potential Clinical Importance (time frame: 12 to 24 weeks at each dose level). 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 23 Jun 2021.