Hereditary Angioedema (HAE)Phase 2NCT01756157
Subcutaneous CINRYZE With Recombinant Human Hyaluronidase for Prevention of Angioedema Attacks
A Phase 2 study testing CINRYZE with rHuPH20 in people with Hereditary Angioedema (HAE), run by Shire at 23 sites in 4 countries.
Trial summary
The primary objectives of the study are to evaluate the safety, tolerability, and efficacy of two doses of CINRYZE with recombinant human hyaluronidase (rHuPH20) administered by subcutaneous (SC) injection to prevent angioedema attacks. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Hereditary Angioedema (HAE)
- What is being tested?
- CINRYZE with rHuPH20
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 23 sitesin 4 countries
- Study dates
- 4 Feb 2013to 13 Sep 2013
- Phase
- Phase 2
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Be ≥12 years of age.
- Have a confirmed diagnosis of Hereditary Angioedema.
Who cannot join
- Receipt of any C1 inhibitor (C1 INH) therapy or any blood products for treatment or prevention of an angioedema attack within 7 days before the first dose of study drug.
- Be receiving prophylactic intravenous CINRYZE that exceeds 1000 units every 3 or 4 days (maximum weekly dose 2000 units).
- Have received any androgen therapy (e.g., danazol, oxandrolone, stanozolol, testosterone) within 7 days prior to the first dose of study drug.
- If female, have started taking or changed the dose of any hormonal contraceptive regimen or hormone replacement therapy (i.e., estrogen/progestin containing products) within 3 months prior to the first dose of study drug.
- History of allergic reaction to C1 INH products, including CINRYZE or other blood products.
- History of abnormal blood clotting.
- Have a known allergy to hyaluronidase or any other ingredient in the study formulation.
Trial locations and contacts
23 sites in 4 countries.
23 sites in 4 countries
United States17 sites
ViroPharma Investigational Site
Bentonville, Arkansas, 72712
ViroPharma Investigational Site
Birmingham, Alabama, 35209
ViroPharma Investigational Site
Boston, Massachusetts, 02114
ViroPharma Investigational Site
Cincinnati, Ohio, 45267
ViroPharma Investigational Site
Colorado Springs, Colorado, 80907
ViroPharma Investigational Site
Columbus, Ohio, 43235
ViroPharma Investigational Site
Dallas, Texas, 75231
ViroPharma Investigational Site
Hershey, Pennsylvania, 17033
ViroPharma Investigational Site
Knoxville, Tennessee, 37909
ViroPharma Investigational Site
Lake Oswego, Oregon, 97035
ViroPharma Investigational Site
Las Vegas, Nevada, 89106
ViroPharma Investigational Site
Mineola, New York, 11501
ViroPharma Investigational Site
Pittsburgh, Pennsylvania, 15241
ViroPharma Investigational Site
Scottsdale, Arizona, 85251
ViroPharma Investigational Site
Spokane, Washington, 99204
ViroPharma Investigational Site
Tampa, Florida, 33613
ViroPharma Investigational Site
Walnut Creek, California, 94598
Germany4 sites
ViroPharma Investigational Site
Berlin
ViroPharma Investigational Site
Essen
ViroPharma Investigational Site
Mainz
ViroPharma Investigational Site
München
About this study
Official title: A Phase 2, Randomized, Double-Blind, Multicenter, Dose-Ranging, Crossover Study to Evaluate the Safety and Efficacy of Subcutaneous Administration of CINRYZE® (C1 Esterase Inhibitor [Human]) With Recombinant Human Hyaluronidase (rHuPH20) for the Prevention of Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema
The primary objectives of the study are to evaluate the safety, tolerability, and efficacy of two doses of CINRYZE with recombinant human hyaluronidase (rHuPH20) administered by subcutaneous (SC) injection to prevent angioedema attacks.
- Conditions
- Hereditary Angioedema (HAE)
- Being tested
- CINRYZE with rHuPH20
- Keywords
- Crossover, C1 esterase inhibitor, Prevention, C1 inhibitor, Hereditary Angioedema, Subcutaneous, Recombinant human hyaluronidase
- 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 with rHuPH20Biological
Also called C1 esterase inhibitor (human), Recombinant human hyaluronidase
| Study group | Role | What they receive |
|---|---|---|
| SC CINRYZE with rHuPH20 Dose Level 1 followed by Dose Level 2 | Experimental | SC CINRYZE with rHuPH20 Dose Level 1 twice weekly (every 3 or 4 days) for 8 weeks followed by SC CINRYZE with rHuPH20 Dose Level 2 twice weekly (every 3 or 4 days) for 8 weeks. Receives: Biological: CINRYZE with rHuPH20 |
| SC CINRYZE with rHuPH20 Dose Level 2 followed by Dose Level 1 | Experimental | SC CINRYZE with rHuPH20 Dose Level 2 twice weekly (every 3 or 4 days) for 8 weeks followed by SC CINRYZE with rHuPH20 Dose Level 1 twice weekly (every 3 or 4 days) for 8 weeks. Receives: Biological: CINRYZE with rHuPH20 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Normalized Number of Angioedema Attacks During the Treatment Period
Angioedema attack was defined as the participant-reported indication of symptoms or signs such as swelling or pain at any location following a report of no swelling or pain on the previous day. Manifestations of an attack that progress from one site to another, prior to complete resolution, was considered a single attack. Attacks that began to regress and then worsened before complete resolution was also considered one attack. Participants who were dosed but did not have any attacks in the period were assigned a value of zero. The number of attacks was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.
Measured: From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Secondary outcomes (4)
Cumulative Attack-severity During the Treatment Period
Cumulative Attack-severity score was the sum of maximum symptom severity recorded for each angioedema attack, determined on the last day of symptoms and recorded as None=0, Mild=1, Moderate=2, and Severe=3 and summing over the unique attacks, yields a Cumulative Attack-severity score. None: no angioedema attack symptom; Mild: the angioedema attack symptom was noticeable to the participant but was easily tolerated and did not interfere with routine activities; Moderate: the angioedema attack symptom interfered with work/school or the ability to participate in family life and social activities; Severe: the angioedema attack symptom significantly limited the participant's ability to attend work/school or participate in family life and social activities. Cumulative attack-severity was normalized for the number of days participants participated in a given period and expressed as the monthly frequency. The scores ranged from 0 to 168 and higher scores represent worse symptoms.
Measured: From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Cumulative Daily-severity During the Treatment Period
Cumulative Daily-severity score was the sum of the severity scores recorded for every day of reported symptoms during the treatment period. Severity scores were recorded as None=0, Mild=1, Moderate=2, and Severe=3. None: no angioedema attack symptom; Mild: the angioedema attack symptom was noticeable to the participant but was easily tolerated and did not interfere with routine activities; Moderate: the angioedema attack symptom interfered with work/school or the ability to participate in family life and social activities; Severe: the angioedema attack symptom significantly limited the participant's ability to attend work/school or participate in family life and social activities. Cumulative daily severity was normalized for the number of days participants participated in a given period and expressed as the monthly frequency. The scores ranged from 0 to 168 and higher scores represent worse symptoms.
Measured: From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Cumulative Symptomatic Days During the Treatment Period
Cumulative symptomatic days was defined as the sum of the symptomatic days of each angioedema attack reported during the treatment period. Participants who were dosed but did not have any attacks in the period were assigned a value of zero. Cumulative symptomatic days was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.
Measured: From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Number of Angioedema Attacks Requiring Acute Treatment During the Treatment Period
Angioedema attack was defined as the participant-reported indication of symptoms or signs such as swelling or pain at any location following a report of no swelling or pain on the previous day. Manifestations of an attack that progress from one site to another, prior to complete resolution, was considered a single attack. Attacks that began to regress and then worsened before complete resolution was also considered one attack. Participants who were dosed but did not have any attacks in the period were assigned a value of zero. The number of attacks was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.
Measured: From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Dec 2012 (estimated)
- Study start4 Feb 2013
- Primary completion13 Sep 2013
- Study completion13 Sep 2013
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.
- Publications (2)Papers the sponsor has linked to this study.
- 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 47 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
- NCT01756157
- Sponsor's protocol ID
- 0624-206
- Other IDs
- 2012-000083-24
- Status last verified
- May 2021
- First submitted
- 29 Jun 2012
- Last updated
- 3 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Riedl MA, Lumry WR, Li HH, Banerji A, Bernstein JA, Ba M, Bjrkander J, Magerl M, Maurer M, Rockich K, Chen H, Schranz J. Subcutaneous administration of human C1 inhibitor with recombinant human hyaluronidase in patients with hereditary angioedema. Allergy Asthma Proc. 2016 Nov;37(6):489-500. doi: 10.2500/aap.2016.37.4006.
PubMed 27931305Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.
PubMed 36326435
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-Blind, Multicenter, Dose-Ranging, Crossover Study to Evaluate the Safety and Efficacy of Subcutaneous Administration of CINRYZE® (C1 Esterase Inhibitor [Human]) With Recombinant Human Hyaluronidase (rHuPH20) for the Prevention of Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema
- ClinicalTrials.gov ID
- NCT01756157
- Acronym / sponsor ID
- 0624-206
- Conditions
- Hereditary Angioedema (HAE)
- Keywords
- Crossover, C1 esterase inhibitor, Prevention, C1 inhibitor, Hereditary Angioedema, Subcutaneous, Recombinant human hyaluronidase
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- ShireIndustry (pharma, biotech, devices)
- Study start
- 4 Feb 2013 (actual)
- Primary completion
- 13 Sep 2013 (actual)
- Study completion
- 13 Sep 2013 (actual)
- First posted
- 25 Dec 2012 (estimated)
- Results
- Posted 12 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objectives of the study are to evaluate the safety, tolerability, and efficacy of two doses of CINRYZE with recombinant human hyaluronidase (rHuPH20) administered by subcutaneous (SC) injection to prevent angioedema attacks.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SC CINRYZE with rHuPH20 Dose Level 1 followed by Dose Level 2 | Experimental | Biological: CINRYZE with rHuPH20SC CINRYZE with rHuPH20 Dose Level 1 twice weekly (every 3 or 4 days) for 8 weeks followed by SC CINRYZE with rHuPH20 Dose Level 2 twice weekly (every 3 or 4 days) for 8 weeks. |
| SC CINRYZE with rHuPH20 Dose Level 2 followed by Dose Level 1 | Experimental | Biological: CINRYZE with rHuPH20SC CINRYZE with rHuPH20 Dose Level 2 twice weekly (every 3 or 4 days) for 8 weeks followed by SC CINRYZE with rHuPH20 Dose Level 1 twice weekly (every 3 or 4 days) for 8 weeks. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Be ≥12 years of age.
- Have a confirmed diagnosis of Hereditary Angioedema.
Key exclusion criteria (7 listed)
- Receipt of any C1 inhibitor (C1 INH) therapy or any blood products for treatment or prevention of an angioedema attack within 7 days before the first dose of study drug.
- Be receiving prophylactic intravenous CINRYZE that exceeds 1000 units every 3 or 4 days (maximum weekly dose 2000 units).
- Have received any androgen therapy (e.g., danazol, oxandrolone, stanozolol, testosterone) within 7 days prior to the first dose of study drug.
- If female, have started taking or changed the dose of any hormonal contraceptive regimen or hormone replacement therapy (i.e., estrogen/progestin containing products) within 3 months prior to the first dose of study drug.
- History of allergic reaction to C1 INH products, including CINRYZE or other blood products.
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 with rHuPH20Also: C1 esterase inhibitor (human), Recombinant human hyaluronidase | Biological | SC CINRYZE with rHuPH20 Dose Level 1 followed by Dose Level 2, SC CINRYZE with rHuPH20 Dose Level 2 followed by Dose Level 1 |
Primary outcome
Normalized Number of Angioedema Attacks During the Treatment Period
Time frame: From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Angioedema attack was defined as the participant-reported indication of symptoms or signs such as swelling or pain at any location following a report of no swelling or pain on the previous day. Manifestations of an attack that progress from one site to another, prior to complete resolution, was considered a single attack. Attacks that began to regress and then worsened before complete resolution was also considered one attack. Participants who were dosed but did not have any attacks in the period were assigned a value of zero. The number of attacks was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.
4 secondary outcomes
Cumulative Attack-severity During the Treatment Period
Time frame: From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Cumulative Daily-severity During the Treatment Period
Time frame: From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Cumulative Symptomatic Days During the Treatment Period
Time frame: From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Number of Angioedema Attacks Requiring Acute Treatment During the Treatment Period
Time frame: From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27931305Riedl MA, Lumry WR, Li HH, Banerji A, Bernstein JA, Ba M, Bjrkander J, Magerl M, Maurer M, Rockich K, Chen H, Schranz J. Subcutaneous administration of human C1 inhibitor with recombinant human hyaluronidase in patients with hereditary angioedema. Allergy Asthma Proc. 2016 Nov;37(6):489-500. doi: 10.2500/aap.2016.37.4006.
- Derived from this study: PubMed 36326435Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2.
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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
23 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CINRYZE with rHuPH20 in people with Hereditary Angioedema (HAE), run by Shire at 23 sites in 4 countries.
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 2 inclusion and 7 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 3 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 23 sites in United States, Germany, Spain, Sweden. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 12 Jun 2015). 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?
Normalized Number of Angioedema Attacks During the Treatment Period (time frame: From Visit 1 (Week 1) up to Visit 16 (Week 8) during each treatment period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01756157, which also lists 2 linked publications.
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 3 Jun 2021.