Trial Outcomes & Findings for A Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE (NCT NCT00914966)
NCT ID: NCT00914966
Last Updated: 2021-06-23
Results Overview
Events reported during the 3 month follow-up period are counted with the dose level at which they occurred.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
20 participants
Primary outcome timeframe
12 to 24 weeks at each dose level
Results posted on
2021-06-23
Participant Flow
Participant milestones
| Measure |
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 (starting dosing regimen for all subjects in the study) - 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
|
|---|---|
|
Step 1: 1500 Units
STARTED
|
20
|
|
Step 1: 1500 Units
COMPLETED
|
18
|
|
Step 1: 1500 Units
NOT COMPLETED
|
2
|
|
Step 2: 2000 Units
STARTED
|
13
|
|
Step 2: 2000 Units
COMPLETED
|
12
|
|
Step 2: 2000 Units
NOT COMPLETED
|
1
|
|
Step 3: 2500 Units
STARTED
|
12
|
|
Step 3: 2500 Units
COMPLETED
|
12
|
|
Step 3: 2500 Units
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
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 (starting dosing regimen for all subjects in the study) - 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
|
|---|---|
|
Step 1: 1500 Units
Withdrawal by Subject
|
1
|
|
Step 1: 1500 Units
Physician Decision
|
1
|
|
Step 2: 2000 Units
Withdrawal by Subject
|
1
|
Baseline Characteristics
A Study to Evaluate the Safety and Effect of Escalating Doses of CINRYZE
Baseline characteristics by cohort
| Measure |
CINRYZE
n=20 Participants
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 (starting dosing regimen for all subjects in the study) - 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
|
|---|---|
|
Age, Continuous
|
41.7 years
STANDARD_DEVIATION 15.28 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 to 24 weeks at each dose levelEvents reported during the 3 month follow-up period are counted with the dose level at which they occurred.
Outcome measures
| Measure |
Step 1: 1500 Units
n=20 Participants
1500 Units of CINRYZE (C1 inhibitor \[human\]) administered by IV infusion twice per week for 12 weeks.
|
Step 2: 2000 Units
n=13 Participants
2000 Units of CINRYZE (C1 inhibitor \[human\]) administered by IV infusion twice per week for 12 weeks.
|
Step 3: 2500 Units
n=12 Participants
2500 Units of CINRYZE (C1 inhibitor \[human\]) administered by IV infusion twice per week for 12 weeks.
|
|---|---|---|---|
|
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
Toxicity grade increases in laboratory parameters
|
6 participants
|
2 participants
|
3 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
Adverse events
|
15 participants
|
11 participants
|
11 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
Hospitalizations
|
0 participants
|
1 participants
|
0 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
Systemic thrombotic events
|
0 participants
|
0 participants
|
0 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
Local/catheter-related thrombotic events
|
1 participants
|
0 participants
|
0 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
Treatment-emergent C1 INH antibodies
|
0 participants
|
0 participants
|
1 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
Potential clinically important vital signs changes
|
3 participants
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: 12 weeks at each dose levelTwo 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.
Outcome measures
| Measure |
Step 1: 1500 Units
n=20 Participants
1500 Units of CINRYZE (C1 inhibitor \[human\]) administered by IV infusion twice per week for 12 weeks.
|
Step 2: 2000 Units
n=13 Participants
2000 Units of CINRYZE (C1 inhibitor \[human\]) administered by IV infusion twice per week for 12 weeks.
|
Step 3: 2500 Units
n=12 Participants
2500 Units of CINRYZE (C1 inhibitor \[human\]) administered by IV infusion twice per week for 12 weeks.
|
|---|---|---|---|
|
Treatment Effect of Escalating Doses of CINRYZE on HAE Attack Rates
Reduction of >1 attack/month from historical rate
|
1 participants
|
0 participants
|
2 participants
|
|
Treatment Effect of Escalating Doses of CINRYZE on HAE Attack Rates
Per-protocol Success
|
4 participants
|
0 participants
|
5 participants
|
|
Treatment Effect of Escalating Doses of CINRYZE on HAE Attack Rates
Investigator-determined Success
|
1 participants
|
0 participants
|
1 participants
|
|
Treatment Effect of Escalating Doses of CINRYZE on HAE Attack Rates
Non-responder
|
1 participants
|
1 participants
|
4 participants
|
Adverse Events
Step 1: 1500 Units
Serious events: 1 serious events
Other events: 12 other events
Deaths: 0 deaths
Step 2: 2000 Units
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Step 3: 2500 Units
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
All Subjects
Serious events: 2 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Step 1: 1500 Units
n=20 participants at risk
1500 Units of CINRYZE (C1 inhibitor \[human\]) administered by IV infusion twice per week for 12 weeks
|
Step 2: 2000 Units
n=13 participants at risk
2000 Units of CINRYZE (C1 inhibitor \[human\]) administered by IV infusion twice per week for 12 weeks
|
Step 3: 2500 Units
n=12 participants at risk
2500 Units of CINRYZE (C1 inhibitor \[human\]) administered by IV infusion twice per week for 12 weeks
|
All Subjects
n=20 participants at risk
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/20 • 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.
|
7.7%
1/13 • 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.
|
0.00%
0/12 • 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.
|
5.0%
1/20 • 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.
|
|
Congenital, familial and genetic disorders
Hereditary angioedema
|
5.0%
1/20 • 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.
|
0.00%
0/13 • 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.
|
0.00%
0/12 • 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.
|
5.0%
1/20 • 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.
|
|
Hepatobiliary disorders
Bile duct stone
|
0.00%
0/20 • 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.
|
7.7%
1/13 • 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.
|
0.00%
0/12 • 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.
|
5.0%
1/20 • 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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cerebral hygroma
|
0.00%
0/20 • 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.
|
0.00%
0/13 • 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.
|
8.3%
1/12 • 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.
|
5.0%
1/20 • 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.
|
Other adverse events
| Measure |
Step 1: 1500 Units
n=20 participants at risk
1500 Units of CINRYZE (C1 inhibitor \[human\]) administered by IV infusion twice per week for 12 weeks
|
Step 2: 2000 Units
n=13 participants at risk
2000 Units of CINRYZE (C1 inhibitor \[human\]) administered by IV infusion twice per week for 12 weeks
|
Step 3: 2500 Units
n=12 participants at risk
2500 Units of CINRYZE (C1 inhibitor \[human\]) administered by IV infusion twice per week for 12 weeks
|
All Subjects
n=20 participants at risk
|
|---|---|---|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
15.0%
3/20 • 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.
|
30.8%
4/13 • 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.
|
25.0%
3/12 • 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.
|
25.0%
5/20 • 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.
|
|
Infections and infestations
Nasopharyngitis
|
15.0%
3/20 • 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.
|
0.00%
0/13 • 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.
|
0.00%
0/12 • 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.
|
15.0%
3/20 • 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.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
5.0%
1/20 • 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.
|
0.00%
0/13 • 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.
|
8.3%
1/12 • 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.
|
10.0%
2/20 • 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.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.0%
1/20 • 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.
|
0.00%
0/13 • 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.
|
8.3%
1/12 • 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.
|
10.0%
2/20 • 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.
|
|
Gastrointestinal disorders
Diarrhea
|
10.0%
2/20 • 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.
|
0.00%
0/13 • 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.
|
0.00%
0/12 • 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.
|
10.0%
2/20 • 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.
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
5.0%
1/20 • 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.
|
7.7%
1/13 • 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.
|
8.3%
1/12 • 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.
|
10.0%
2/20 • 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.
|
|
General disorders
Medical device complication
|
10.0%
2/20 • 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.
|
0.00%
0/13 • 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.
|
0.00%
0/12 • 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.
|
10.0%
2/20 • 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.
|
|
General disorders
Peripheral edema
|
10.0%
2/20 • 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.
|
0.00%
0/13 • 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.
|
0.00%
0/12 • 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.
|
10.0%
2/20 • 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.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.0%
1/20 • 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.
|
7.7%
1/13 • 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.
|
8.3%
1/12 • 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.
|
10.0%
2/20 • 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.
|
|
Infections and infestations
Rhinitis
|
0.00%
0/20 • 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.
|
7.7%
1/13 • 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.
|
8.3%
1/12 • 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.
|
10.0%
2/20 • 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.
|
|
Infections and infestations
Sinusitis
|
5.0%
1/20 • 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.
|
0.00%
0/13 • 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.
|
8.3%
1/12 • 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.
|
10.0%
2/20 • 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.
|
|
Infections and infestations
Urinary tract infection
|
5.0%
1/20 • 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.
|
0.00%
0/13 • 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.
|
16.7%
2/12 • 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.
|
10.0%
2/20 • 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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Clinical Study Agreement. Most restrictive provision - PI will not publish results until after first of: multicenter publication is published or 24 months from study end. Thereafter, PI may publish his results. PI must provide copy of proposed publication to Sponsor for pre-review. If Sponsor requests, PI must delete Sponsor confidential information before publication and/or delay publication for 60 days so Sponsor can file for patents or take other action to protect its patent rights.
- Publication restrictions are in place
Restriction type: OTHER