Hereditary Angioedema (HAE)
Conditions
Keywords
CINRYZE, C1 INH, HAE, C1 inhibitor, Pediatric, PK/PD
Brief summary
The objectives of this study were to evaluate: (1) the dose response and (2) the pharmacokinetics (PK) and pharmacodynamics (PD) of intravenous (IV) administration of CINRYZE for the treatment of acute angioedema attacks in children above and below 25 kg and less than 12 years of age with hereditary angioedema (HAE); and (3) to determine the safety and tolerability following IV administration of CINRYZE in this study population.
Detailed description
Each subject received CINRYZE for treatment of a single acute angioedema attack.
Interventions
BIOLOGICALCINRYZE
Sponsors
Shire
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
To be eligible for this protocol, subjects must: 1. Be at least 10 kg of body weight. 2. Have a confirmed diagnosis of HAE. 3. Have an acute HAE attack and be able to initiate treatment within 8 hours after onset of symptoms.
Exclusion criteria
To be eligible for this protocol, subjects must not: 1. Have any active infectious illness. 2. Have had a prior HAE attack and/or received any C1 INH product within 7 days prior to dosing with study drug. 3. Have received therapy with antifibrinolytics (e.g., tranexamic acid), androgens (e.g., danazol, oxandrolone, stanozolol, or testosterone), ecallantide (Kalbitor®), or icatibant (Firazyr®) within 7 days prior to dosing with study drug. 4. Have a history of allergic reaction to C1 INH products, including CINRYZE (or any of the components of CINRYZE), or other blood products. 5. Have participated in any other investigational drug evaluation within 30 days prior to dosing with study drug, or have previously received treatment with CINRYZE in this study at any time.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Presence of Unequivocal Beginning of Relief of the Defining Attack Symptom | Within 4 hours following treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Unequivocal Beginning of Relief of the Defining Attack Symptom | Within 4 hours following treatment | — |
| Time to Complete Resolution of the Attack | Within 1 week following treatment | — |
| Change in C1 Inhibitor (C1 INH) Antigen and Functional C1 INH Concentrations | Pre-dose, 2, 4, 8 hours post dose on Day 1; Day 2, 3, 5, 8 | Data was not reported due to change in planned analysis. |
Countries
Germany, Hungary, United States
Participant flow
Recruitment details
Participants were not enrolled in the lower body weight category (10-25 kilograms \[kg\]) 1000 Units (U) dose group despite substantial recruitment efforts.
Pre-assignment details
Of 12 participants screened, 9 participants were enrolled and treated. The reason for 3 participants were screen failures as they did not meet the inclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| 500 U CINRYZE (10-25 kg Body Weight) Single IV dose of 500 U CINRYZE | 3 |
| 1000 U CINRYZE (>25 kg Body Weight) Single IV dose of 1000 U CINRYZE | 3 |
| 1500 U CINRYZE (>25 kg Body Weight) Single IV dose of 1500 U CINRYZE | 3 |
| Total | 9 |
Baseline characteristics
| Characteristic | 500 U CINRYZE (10-25 kg Body Weight) | 1000 U CINRYZE (>25 kg Body Weight) | 1500 U CINRYZE (>25 kg Body Weight) | Total |
|---|---|---|---|---|
| Age, Continuous | 7 years | 9 years | 10 years | 9 years |
| Region of Enrollment United States | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 3 | 0 / 3 | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 3 |
Outcome results
Primary
Presence of Unequivocal Beginning of Relief of the Defining Attack Symptom
Time frame: Within 4 hours following treatment
Population: Intent-to-treat efficacy (ITT-E) population included all participants with baseline and at least one post-infusion investigator assessment of the hereditary angioedema (HAE) attack.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 500 U CINRYZE (10-25 kg Body Weight) | Presence of Unequivocal Beginning of Relief of the Defining Attack Symptom | No | 0 participants |
| 500 U CINRYZE (10-25 kg Body Weight) | Presence of Unequivocal Beginning of Relief of the Defining Attack Symptom | Yes | 3 participants |
| 1000 U CINRYZE (>25 kg Body Weight) | Presence of Unequivocal Beginning of Relief of the Defining Attack Symptom | No | 0 participants |
| 1000 U CINRYZE (>25 kg Body Weight) | Presence of Unequivocal Beginning of Relief of the Defining Attack Symptom | Yes | 3 participants |
| 1500 U CINRYZE (>25 kg Body Weight) | Presence of Unequivocal Beginning of Relief of the Defining Attack Symptom | No | 0 participants |
| 1500 U CINRYZE (>25 kg Body Weight) | Presence of Unequivocal Beginning of Relief of the Defining Attack Symptom | Yes | 3 participants |
Secondary
Change in C1 Inhibitor (C1 INH) Antigen and Functional C1 INH Concentrations
Data was not reported due to change in planned analysis.
Time frame: Pre-dose, 2, 4, 8 hours post dose on Day 1; Day 2, 3, 5, 8
Population: No participant agreed to obtain pharmacokinetic (PK) blood sampling for antigenic and functional C1 INH levels. Hence, it was planned not to be analyzed.
Secondary
Time to Complete Resolution of the Attack
Time frame: Within 1 week following treatment
Population: ITT-E population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 500 U CINRYZE (10-25 kg Body Weight) | Time to Complete Resolution of the Attack | 13.58 hours |
| 1000 U CINRYZE (>25 kg Body Weight) | Time to Complete Resolution of the Attack | 10.00 hours |
| 1500 U CINRYZE (>25 kg Body Weight) | Time to Complete Resolution of the Attack | 29.07 hours |
Secondary
Time to Unequivocal Beginning of Relief of the Defining Attack Symptom
Time frame: Within 4 hours following treatment
Population: ITT-E population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 500 U CINRYZE (10-25 kg Body Weight) | Time to Unequivocal Beginning of Relief of the Defining Attack Symptom | 1.25 hours |
| 1000 U CINRYZE (>25 kg Body Weight) | Time to Unequivocal Beginning of Relief of the Defining Attack Symptom | 0.25 hours |
| 1500 U CINRYZE (>25 kg Body Weight) | Time to Unequivocal Beginning of Relief of the Defining Attack Symptom | 0.50 hours |