CompletedNCT00914966Updated Jun 23, 2021Results posted

A Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE

A Phase 4 interventional study of C1 inhibitor (human) [C1 INH] in Hereditary Angioedema, sponsored by Shire. Completed at 11 sites in United States. Open to participants aged 6 Years and older. Per ClinicalTrials.gov, last updated 2021-06-23.

Sponsored by Shire · Phase 4, Interventional, and Prevention

Phase: Phase 4
Study type: Interventional
Enrollment: 20
Allocation: Not applicable
Ages: 6 Years and older
Sex: All

Study summary

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 studied

Hereditary Angioedema

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In context

Angioedema

164 studies on the registry are indexed under Angioedema; 19 are open to participants now.

This study's enrollment of 20 is below the median of 44 across 111 interventional studies indexed under Angioedema.

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Lead sponsor

Shire is the lead sponsor of 346 studies on the registry; 2 are open to participants now.

Of its 47 completed or terminated interventional studies of FDA-regulated products, 47 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 6 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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
- 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).

Exclusion criteria

Exclusion Criteria:

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).
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.

Study design

Phase: Phase 4
Primary purpose: Prevention
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 20 participants (actual)

Study arms

Experimental
CINRYZE
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
Biological: C1 inhibitor (human) [C1 INH]

Interventions

BiologicalC1 inhibitor (human) [C1 INH]
Also known as: CINRYZE, C1 esterase inhibitor (human)

What researchers measure

Primary outcomes

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.
Time frame: 12 to 24 weeks at each dose level

Secondary outcomes

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.
Time frame: 12 weeks at each dose level

Results

Posted Jul 18, 2013

Limitations and caveats

Per Changes in the Planned Analyses: The clinical presentation of disease manifestations and response to therapy are highly variable among patients with HAE and as such, the efficacy results from this study are presented in this report by individual participant in narrative summaries rather than as summary statistics. Thus, one outcome measure (Use of rescue therapy and/or other therapy for treatment of HAE symptoms) is not presented.

Participant flow

Step 1: 1500 Units

Participant flow — Step 1: 1500 Units
Milestone	CINRYZE
Started	20
Completed	18
Not completed	2
Withdrew: Withdrawal by subject	1
Withdrew: Physician decision	1

Step 2: 2000 Units

Participant flow — Step 2: 2000 Units
Milestone	CINRYZE
Started	13
Completed	12
Not completed	1
Withdrew: Withdrawal by subject	1

Step 3: 2500 Units

Participant flow — Step 3: 2500 Units
Milestone	CINRYZE
Started	12
Completed	12
Not completed	0

Outcome measures

PrimaryNumber 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.

Time frame:: 12 to 24 weeks at each dose level
Reported as:: Number · participants

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
participants	Step 1: 1500 Units	Step 2: 2000 Units	Step 3: 2500 Units
Adverse events	15	11	11
Hospitalizations	0	1	0
Systemic thrombotic events	0	0	0
Local/catheter-related thrombotic events	1	0	0
Treatment-emergent C1 INH antibodies	0	0	1
Toxicity grade increases in laboratory parameters	6	2	3
Potential clinically important vital signs changes	3	1	1

SecondaryTreatment 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.

Time frame:: 12 weeks at each dose level
Reported as:: Number · participants

Treatment Effect of Escalating Doses of CINRYZE on HAE Attack Rates
participants	Step 1: 1500 Units	Step 2: 2000 Units	Step 3: 2500 Units
Per-protocol Success	4	0	5
Investigator-determined Success	1	0	1
Reduction of >1 attack/month from historical rate	1	0	2
Non-responder	1	1	4

Adverse events

Collected over 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.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Step 1: 1500 Units	—	1/20 (5%)	12/20 (60%)
Step 2: 2000 Units	—	1/13 (7.7%)	5/13 (38.5%)
Step 3: 2500 Units	—	1/12 (8.3%)	6/12 (50%)
All Subjects	—	2/20 (10%)	13/20 (65%)

Most frequent serious events

Most frequent serious events
Event	Step 1: 1500 Units	Step 2: 2000 Units	Step 3: 2500 Units	All Subjects
Cerebral hygromaNeoplasms benign, malignant and unspecified (incl cysts and polyps)	0/20	0/13	1/12	1/20
AnemiaBlood and lymphatic system disorders	0/20	1/13	0/12	1/20
Bile duct stoneHepatobiliary disorders	0/20	1/13	0/12	1/20
Hereditary angioedemaCongenital, familial and genetic disorders	1/20	0/13	0/12	1/20

Most frequent other events

Showing 10 of 12

Most frequent other events
Event	Step 1: 1500 Units	Step 2: 2000 Units	Step 3: 2500 Units	All Subjects
Upper respiratory tract infectionInfections and infestations	3/20	4/13	3/12	5/20
Urinary tract infectionInfections and infestations	1/20	0/13	2/12	2/20
NasopharyngitisInfections and infestations	3/20	0/13	0/12	3/20
Abdominal discomfortGastrointestinal disorders	1/20	0/13	1/12	2/20
ArthralgiaMusculoskeletal and connective tissue disorders	1/20	0/13	1/12	2/20
DiarrheaGastrointestinal disorders	2/20	0/13	0/12	2/20
Ligament sprainInjury, poisoning and procedural complications	1/20	1/13	1/12	2/20
Medical device complicationGeneral disorders	2/20	0/13	0/12	2/20
Peripheral edemaGeneral disorders	2/20	0/13	0/12	2/20
Pain in extremityMusculoskeletal and connective tissue disorders	1/20	1/13	1/12	2/20

Baseline characteristics

Age, Continuous
Age, Continuous(years)	CINRYZE
Mean	41.7 ± 15.28

Sex: Female, Male
Sex: Female, Male(Participants)	CINRYZE
Female	14
Male	6

Study locations

11 sites

Allergy, Asthma and Immunology Associates
Scottsdale, Arizona 85251, United States
Family Allergy and Asthma Center
Atlanta, Georgia 30342, United States
Institute for Asthma and Allergy
Wheaton, Maryland 20902, United States
Winthrop University Hospital
Mineola, New York 11501, United States
University of Cincinnati Medical Center
Cincinnati, Ohio 45267, United States
Allergy and Asthma Research Group
Eugene, Oregon 97401, United States
Baker Allergy, Asthma and Dermatology Research Center
Lake Oswego, Oregon 97035, United States
East Tennessee Center for Clinical Research
Knoxville, Tennessee 37909, United States
Bryan, Texas 77802, United States
AARA Research Center
Dallas, Texas 75231, United States
Marycliff Allergy Specialist
Spokane, Washington 99204, United States

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 23, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00914966
Lead sponsor: Shire
Responsible party: Sponsor
First posted: Jun 5, 2009
Start date: Aug 31, 2009
Primary completion: May 24, 2012
Completion: May 24, 2012
Results posted: Jul 18, 2013
Last update: Jun 23, 2021

Study contacts

Study Director

study director · Takeda

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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