Hereditary Angioedema (HAE)
Conditions
Keywords
Pediatric, C1 inhibitor, HAE, Cinryze, C1 INH, Prevention
Brief summary
Primary Objective - To assess the relative efficacy of two dose levels of CINRYZE (500 Units and 1000 Units) administered by intravenous (IV) injection every 3 or 4 days to prevent angioedema attacks in children 6 to 11 years of age with hereditary angioedema (HAE). Secondary Objectives - To assess the safety and tolerability, characterize the pharmacokinetics (PK) and pharmacodynamics (PD), and assess the immunogenicity of two dose levels of CINRYZE administered by IV injection in children 6 to 11 years of age with HAE.
Interventions
BIOLOGICALCINRYZE 500
500 Units of CINRYZE administered by IV injection
BIOLOGICALCINRYZE 1000
1000 Units of CINRYZE administered by IV injection
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
6 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Type I or Type II HAE. * History of angioedema attacks.
Exclusion criteria
* History of bleeding or clotting abnormality. * Diagnosis of acquired angioedema or known to have C1 INH antibodies. * History of allergic reaction to C1 esterase inhibitor or other blood products. * Receipt of any experimental agents other than those required for prevention or treatment of angioedema attacks within 30 days prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Normalized Number of Angioedema Attacks Per Month in a Treatment Period | From start of treatment up to 12 weeks 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. Attacks that began then appeared to resolve and then reappeared without a symptom-free calendar day reported after the appearance of resolution were considered 1 attack. Any events of swelling due to trauma or symmetrical nonpainful swelling of the lower extremities were not considered an angioedema attack. The number of attacks was normalized for the number of days participants participated in a given period and expressed as the monthly frequency. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With C1 Esterase Inhibitor (C1 INH) Antibodies in Plasma | Pre-dose, 1 week post treatment (Week 13, Week 25) and 1 month post treatment follow-up (Week 28) | The presence of C1 INH antibodies in plasma samples was determined using a proprietary enzyme-linked-immunosorbent-assay. Number of participants with C1 INH Antibodies was reported. |
| Cumulative Daily-severity Score of Angioedema Attacks Normalized Per Month in a Treatment Period | From start of treatment up to 12 weeks during each intervention period | Severity of the angioedema attack sign/symptom was characterized as None: no symptom; Mild: noticeable but easily tolerated by the participant and did not interfere with routine activities; Moderate: interfered with the participant's ability to attend school or participate in family life and social/recreational activities; Severe: significantly limited the participant's ability to attend school or participate in family life and social/recreational activities. Symptom severity score was assigned as Mild = 1, Moderate = 2 and Severe = 3. Cumulative daily-severity score was the sum of the severity scores recorded for every day of reported symptoms in a treatment period. Cumulative daily-severity score normalized per month \[(raw score/number of days of participation in that treatment period)\*30.4\] was reported here. Cumulative daily-severity score normalized per month ranged from 0 to 15.6 and higher scores represent worse symptoms. |
| Normalized Number of Angioedema Attacks Per Month Requiring Acute Treatment in a Treatment Period | From start of treatment up to 12 weeks during each intervention 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. Attacks that began then appeared to resolve and then reappeared without a symptom-free calendar day reported after the appearance of resolution were considered 1 attack. Any events of swelling due to trauma or symmetrical nonpainful swelling of the lower extremities were not considered an angioedema attack. The number of attacks requiring acute treatment was normalized for the number of days participants participated in a given period and expressed as the monthly frequency. |
| Cumulative Attack-severity Score of Angioedema Attacks Normalized Per Month in a Treatment Period | From start of treatment up to 12 weeks during each treatment period | Severity of the angioedema attack sign/symptom was characterized as None: no symptom; Mild: noticeable symptom but easily tolerated by the participant and did not interfere with routine activities; Moderate: symptom interfered with the participant's ability to attend school or participate in family life and social/recreational activities; Severe: symptom significantly limited the participant's ability to attend school or participate in family life and social/recreational activities. Symptom severity score was assigned as Mild = 1, Moderate = 2 and Severe = 3. Cumulative attack severity score was the sum of the maximum symptom severity scores recorded for each angioedema attack in a treatment period. Cumulative attack-severity score normalized per month \[(raw score/number of days of participation in that treatment period)\*30.4\] was reported here. Cumulative attack-severity score normalized per month ranged from 0 to 10.4 and higher scores represent worse symptoms. |
| Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Pre-dose and 1 hour (h) post-dose at Week 1 (Dose 1) and Week 6 (Dose 12); Pre-dose, 1, 2, 4 and 8 h post-dose at Week 12 (Dose 24) of each intervention period | C1 INH antigen concentration in plasma was determined using an automated nephelometric assay. |
| C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Pre-dose and 1 h post-dose at Week 1 (Dose 1) and Week 6 (Dose 12); Pre-dose, 1, 2, 4 and 8 h post-dose at Week 12 (Dose 24) of each intervention period | The functional activity of C1 INH in plasma samples was determined by a chromogenic assay. |
| Plasma Concentration of Complement C4 | Pre-dose and 1 h post-dose at Week 1 (Dose 1) and Week 6 (Dose 12); Pre-dose, 1, 2, 4 and 8 h post-dose at Week 12 (Dose 24) of each intervention period | Concentration of Complement C4 in plasma was determined using an automated nephelometric assay. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Dose Group | From start of study treatment up to 25 weeks | An adverse event (AE) was any untoward, undesired, unplanned clinical event in the form of signs, symptoms, disease, or laboratory or physiological observations occurring in a participant participating in a clinical study with the sponsor's product, regardless of causal relationship. TEAEs were defined as events that started or worsened on or after the date and time of the first dose of investigational product and up to 7 days after the last dose of investigational product. |
Countries
Germany, Israel, Mexico, Romania, United States
Participant flow
Recruitment details
The study was conducted in 10 study centers in the United States, European Union, Mexico, and Israel between 20 March 2014 (first participant first visit) and 04 May 2017 (last participant last visit).
Pre-assignment details
A total of 16 participants were screened and of them, 12 were enrolled into the baseline observational period (12 weeks) and were randomized to receive the treatment in sequence A-B and B-A during this crossover study without a washout period.
Participants by arm
| Arm | Count |
|---|---|
| Treatment A-B (500 U/1000 U CINRYZE) Participants received 500 units (U) of CINRYZE intravenous (IV) injection twice weekly (every 3 or 4 days) for 12 weeks (Treatment A) in Intervention period 1 followed by 1000 U CINRYZE IV injection twice weekly (every 3 or 4 days) for 12 weeks (Treatment B) in Intervention period 2. There was no washout period between two intervention periods. | 5 |
| Treatment B-A (1000 U/500 U CINRYZE) Participants received 1000 U CINRYZE IV injection twice weekly (every 3 or 4 days) for 12 weeks (Treatment B) in Intervention period 1 followed by 500 U CINRYZE IV injection twice weekly (every 3 or 4 days) for 12 weeks (Treatment A) in Intervention period 2. There was no washout period between two intervention periods. | 7 |
| Total | 12 |
Baseline characteristics
| Characteristic | Treatment A-B (500 U/1000 U CINRYZE) | Treatment B-A (1000 U/500 U CINRYZE) | Total |
|---|---|---|---|
| Age, Continuous | 10.2 Years STANDARD_DEVIATION 0.84 | 9.4 Years STANDARD_DEVIATION 1.51 | 9.8 Years STANDARD_DEVIATION 1.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 10 / 12 | 11 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Normalized Number of Angioedema Attacks Per Month in a 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. Attacks that began then appeared to resolve and then reappeared without a symptom-free calendar day reported after the appearance of resolution were considered 1 attack. Any events of swelling due to trauma or symmetrical nonpainful swelling of the lower extremities were not considered an angioedema attack. The number of attacks was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.
Time frame: From start of treatment up to 12 weeks during each treatment period
Population: Full Analysis Set (FAS) included all participants in the safety set who had at least 1 post-baseline primary efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A (500 U CINRYZE) | Normalized Number of Angioedema Attacks Per Month in a Treatment Period | 1.2 Angioedema attacks per month | Standard Deviation 1.53 |
| Treatment B (1000 U CINRYZE) | Normalized Number of Angioedema Attacks Per Month in a Treatment Period | 0.7 Angioedema attacks per month | Standard Deviation 1.35 |
p-value: 0.0390% CI: [-0.71, -0.1]Paired t-test
Secondary
C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma
The functional activity of C1 INH in plasma samples was determined by a chromogenic assay.
Time frame: Pre-dose and 1 h post-dose at Week 1 (Dose 1) and Week 6 (Dose 12); Pre-dose, 1, 2, 4 and 8 h post-dose at Week 12 (Dose 24) of each intervention period
Population: PK set consisted of all pariticipants in the safety set with no major deviations related to investigational product intake and evaluable PK profiles.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A (500 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 1 (Pre-dose 1) | 0.290 Units per milliliter (U/mL) | Standard Deviation 0.0914 |
| Treatment A (500 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 6 (Pre-dose 12) | 0.297 Units per milliliter (U/mL) | Standard Deviation 0.1375 |
| Treatment A (500 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 6 (1 h post-dose 12) | 0.570 Units per milliliter (U/mL) | Standard Deviation 0.119 |
| Treatment A (500 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 12 (Pre-dose 24) | 0.255 Units per milliliter (U/mL) | Standard Deviation 0.1108 |
| Treatment A (500 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 12 (1 h post-dose 24) | 0.531 Units per milliliter (U/mL) | Standard Deviation 0.133 |
| Treatment A (500 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 12 (2 h post-dose 24) | 0.497 Units per milliliter (U/mL) | Standard Deviation 0.0635 |
| Treatment A (500 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 12 (4 h post-dose 24) | 0.497 Units per milliliter (U/mL) | Standard Deviation 0.0058 |
| Treatment A (500 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 12 (8 h post-dose 24) | 0.430 Units per milliliter (U/mL) | Standard Deviation 0.0458 |
| Treatment A (500 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 1 (1 h post-dose 1) | 0.575 Units per milliliter (U/mL) | Standard Deviation 0.1358 |
| Treatment B (1000 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 12 (8 h post-dose 24) | 0.643 Units per milliliter (U/mL) | Standard Deviation 0.0723 |
| Treatment B (1000 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 12 (2 h post-dose 24) | 0.613 Units per milliliter (U/mL) | Standard Deviation 0.2601 |
| Treatment B (1000 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 6 (Pre-dose 12) | 0.336 Units per milliliter (U/mL) | Standard Deviation 0.0933 |
| Treatment B (1000 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 1 (Pre-dose 1) | 0.210 Units per milliliter (U/mL) | Standard Deviation 0.1282 |
| Treatment B (1000 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 6 (1 h post-dose 12) | 0.865 Units per milliliter (U/mL) | Standard Deviation 0.155 |
| Treatment B (1000 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 12 (4 h post-dose 24) | 0.590 Units per milliliter (U/mL) | Standard Deviation 0.1803 |
| Treatment B (1000 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 12 (Pre-dose 24) | 0.362 Units per milliliter (U/mL) | Standard Deviation 0.1897 |
| Treatment B (1000 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 1 (1 h post-dose 1) | 0.725 Units per milliliter (U/mL) | Standard Deviation 0.31 |
| Treatment B (1000 U CINRYZE) | C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma | Week 12 (1 h post-dose 24) | 0.803 Units per milliliter (U/mL) | Standard Deviation 0.1906 |
Secondary
Cumulative Attack-severity Score of Angioedema Attacks Normalized Per Month in a Treatment Period
Severity of the angioedema attack sign/symptom was characterized as None: no symptom; Mild: noticeable symptom but easily tolerated by the participant and did not interfere with routine activities; Moderate: symptom interfered with the participant's ability to attend school or participate in family life and social/recreational activities; Severe: symptom significantly limited the participant's ability to attend school or participate in family life and social/recreational activities. Symptom severity score was assigned as Mild = 1, Moderate = 2 and Severe = 3. Cumulative attack severity score was the sum of the maximum symptom severity scores recorded for each angioedema attack in a treatment period. Cumulative attack-severity score normalized per month \[(raw score/number of days of participation in that treatment period)\*30.4\] was reported here. Cumulative attack-severity score normalized per month ranged from 0 to 10.4 and higher scores represent worse symptoms.
Time frame: From start of treatment up to 12 weeks during each treatment period
Population: FAS included all participants in the safety set who had at least 1 post-baseline primary efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A (500 U CINRYZE) | Cumulative Attack-severity Score of Angioedema Attacks Normalized Per Month in a Treatment Period | 2.0 Score on a scale | Standard Deviation 2.91 |
| Treatment B (1000 U CINRYZE) | Cumulative Attack-severity Score of Angioedema Attacks Normalized Per Month in a Treatment Period | 1.4 Score on a scale | Standard Deviation 2.68 |
p-value: 0.0590% CI: [-1.2, -0.11]Paired t-test
Secondary
Cumulative Daily-severity Score of Angioedema Attacks Normalized Per Month in a Treatment Period
Severity of the angioedema attack sign/symptom was characterized as None: no symptom; Mild: noticeable but easily tolerated by the participant and did not interfere with routine activities; Moderate: interfered with the participant's ability to attend school or participate in family life and social/recreational activities; Severe: significantly limited the participant's ability to attend school or participate in family life and social/recreational activities. Symptom severity score was assigned as Mild = 1, Moderate = 2 and Severe = 3. Cumulative daily-severity score was the sum of the severity scores recorded for every day of reported symptoms in a treatment period. Cumulative daily-severity score normalized per month \[(raw score/number of days of participation in that treatment period)\*30.4\] was reported here. Cumulative daily-severity score normalized per month ranged from 0 to 15.6 and higher scores represent worse symptoms.
Time frame: From start of treatment up to 12 weeks during each intervention period
Population: FAS included all participants in the safety set who had at least 1 post-baseline primary efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A (500 U CINRYZE) | Cumulative Daily-severity Score of Angioedema Attacks Normalized Per Month in a Treatment Period | 4.1 Score on a scale | Standard Deviation 5.01 |
| Treatment B (1000 U CINRYZE) | Cumulative Daily-severity Score of Angioedema Attacks Normalized Per Month in a Treatment Period | 2.2 Score on a scale | Standard Deviation 3.5 |
p-value: 0.0490% CI: [-3.31, -0.38]Paired t-test
Secondary
Normalized Number of Angioedema Attacks Per Month Requiring Acute Treatment in a 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. Attacks that began then appeared to resolve and then reappeared without a symptom-free calendar day reported after the appearance of resolution were considered 1 attack. Any events of swelling due to trauma or symmetrical nonpainful swelling of the lower extremities were not considered an angioedema attack. The number of attacks requiring acute treatment was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.
Time frame: From start of treatment up to 12 weeks during each intervention period
Population: FAS included all participants in the safety set who had at least 1 post-baseline primary efficacy assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A (500 U CINRYZE) | Normalized Number of Angioedema Attacks Per Month Requiring Acute Treatment in a Treatment Period | 0.7 Angioedema attacks per month | Standard Deviation 1.5 |
| Treatment B (1000 U CINRYZE) | Normalized Number of Angioedema Attacks Per Month Requiring Acute Treatment in a Treatment Period | 0.4 Angioedema attacks per month | Standard Deviation 1.27 |
p-value: 0.0790% CI: [-0.41, -0.03]Paired t-test
Secondary
Number of Participants With C1 Esterase Inhibitor (C1 INH) Antibodies in Plasma
The presence of C1 INH antibodies in plasma samples was determined using a proprietary enzyme-linked-immunosorbent-assay. Number of participants with C1 INH Antibodies was reported.
Time frame: Pre-dose, 1 week post treatment (Week 13, Week 25) and 1 month post treatment follow-up (Week 28)
Population: Safety set included all participants who received at least 1 dose of investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A (500 U CINRYZE) | Number of Participants With C1 Esterase Inhibitor (C1 INH) Antibodies in Plasma | 0 Participants |
| Treatment B (1000 U CINRYZE) | Number of Participants With C1 Esterase Inhibitor (C1 INH) Antibodies in Plasma | 0 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Dose Group
An adverse event (AE) was any untoward, undesired, unplanned clinical event in the form of signs, symptoms, disease, or laboratory or physiological observations occurring in a participant participating in a clinical study with the sponsor's product, regardless of causal relationship. TEAEs were defined as events that started or worsened on or after the date and time of the first dose of investigational product and up to 7 days after the last dose of investigational product.
Time frame: From start of study treatment up to 25 weeks
Population: Safety set included all participants who received at least 1 dose of investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment A (500 U CINRYZE) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Dose Group | 10 Participants |
| Treatment B (1000 U CINRYZE) | Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Dose Group | 11 Participants |
Secondary
Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen
C1 INH antigen concentration in plasma was determined using an automated nephelometric assay.
Time frame: Pre-dose and 1 hour (h) post-dose at Week 1 (Dose 1) and Week 6 (Dose 12); Pre-dose, 1, 2, 4 and 8 h post-dose at Week 12 (Dose 24) of each intervention period
Population: Pharmacokinetic (PK) set consisted of all pariticipants in the safety set with no major deviations related to investigational product intake and evaluable PK profiles.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A (500 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 12 (2 h post-dose 24) | 0.1440 Gram per liter (g/L) | Standard Deviation 0.004 |
| Treatment A (500 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 6 (1 h post-dose 12) | 0.1631 Gram per liter (g/L) | Standard Deviation 0.04188 |
| Treatment A (500 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 12 (4 h post-dose 24) | 0.1440 Gram per liter (g/L) | Standard Deviation 0.01131 |
| Treatment A (500 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 6 (Pre-dose 12) | 0.0965 Gram per liter (g/L) | Standard Deviation 0.03129 |
| Treatment A (500 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 12 (8 h post-dose 24) | 0.1280 Gram per liter (g/L) | Standard Deviation 0.0099 |
| Treatment A (500 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 12 (Pre-dose 24) | 0.0823 Gram per liter (g/L) | Standard Deviation 0.02758 |
| Treatment A (500 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 1 (Pre-dose 1) | 0.0945 Gram per liter (g/L) | Standard Deviation 0.03294 |
| Treatment A (500 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 12 (1 h post-dose 24) | 0.1621 Gram per liter (g/L) | Standard Deviation 0.0299 |
| Treatment A (500 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 1 (1 h post-dose 1) | 0.1819 Gram per liter (g/L) | Standard Deviation 0.04331 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 12 (1 h post-dose 24) | 0.2396 Gram per liter (g/L) | Standard Deviation 0.04511 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 1 (1 h post-dose 1) | 0.2084 Gram per liter (g/L) | Standard Deviation 0.08757 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 6 (Pre-dose 12) | 0.1068 Gram per liter (g/L) | Standard Deviation 0.03098 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 6 (1 h post-dose 12) | 0.2543 Gram per liter (g/L) | Standard Deviation 0.05499 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 12 (Pre-dose 24) | 0.1002 Gram per liter (g/L) | Standard Deviation 0.0442 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 12 (2 h post-dose 24) | 0.2070 Gram per liter (g/L) | Standard Deviation 0.01838 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 12 (4 h post-dose 24) | 0.1770 Gram per liter (g/L) | Standard Deviation 0.0297 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 12 (8 h post-dose 24) | 0.1790 Gram per liter (g/L) | Standard Deviation 0.031 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen | Week 1 (Pre-dose 1) | 0.0736 Gram per liter (g/L) | Standard Deviation 0.02885 |
Secondary
Plasma Concentration of Complement C4
Concentration of Complement C4 in plasma was determined using an automated nephelometric assay.
Time frame: Pre-dose and 1 h post-dose at Week 1 (Dose 1) and Week 6 (Dose 12); Pre-dose, 1, 2, 4 and 8 h post-dose at Week 12 (Dose 24) of each intervention period
Population: PK set consisted of all pariticipants in the safety set with no major deviations related to investigational product intake and evaluable PK profiles.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment A (500 U CINRYZE) | Plasma Concentration of Complement C4 | Week 1 (1 h post-dose 1) | 99.7 Milligram per liter (mg/L) | Standard Deviation 36.73 |
| Treatment A (500 U CINRYZE) | Plasma Concentration of Complement C4 | Week 12 (1 h post-dose 24) | 79.2 Milligram per liter (mg/L) | Standard Deviation 20.21 |
| Treatment A (500 U CINRYZE) | Plasma Concentration of Complement C4 | Week 6 (1 h post-dose 12) | 88.0 Milligram per liter (mg/L) | Standard Deviation 27.75 |
| Treatment A (500 U CINRYZE) | Plasma Concentration of Complement C4 | Week 12 (2 h post-dose 24) | 86.7 Milligram per liter (mg/L) | Standard Deviation 4.93 |
| Treatment A (500 U CINRYZE) | Plasma Concentration of Complement C4 | Week 6 (Pre-dose 12) | 97.3 Milligram per liter (mg/L) | Standard Deviation 37.26 |
| Treatment A (500 U CINRYZE) | Plasma Concentration of Complement C4 | Week 12 (4 h post-dose 24) | 89.3 Milligram per liter (mg/L) | Standard Deviation 12.66 |
| Treatment A (500 U CINRYZE) | Plasma Concentration of Complement C4 | Week 12 (Pre-dose 24) | 83.3 Milligram per liter (mg/L) | Standard Deviation 21.63 |
| Treatment A (500 U CINRYZE) | Plasma Concentration of Complement C4 | Week 12 (8 h post-dose 24) | 99.3 Milligram per liter (mg/L) | Standard Deviation 11.02 |
| Treatment A (500 U CINRYZE) | Plasma Concentration of Complement C4 | Week 1 (Pre-dose 1) | 105.1 Milligram per liter (mg/L) | Standard Deviation 39.38 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of Complement C4 | Week 12 (8 h post-dose 24) | 114.7 Milligram per liter (mg/L) | Standard Deviation 30.75 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of Complement C4 | Week 1 (Pre-dose 1) | 71.2 Milligram per liter (mg/L) | Standard Deviation 29.63 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of Complement C4 | Week 1 (1 h post-dose 1) | 71.4 Milligram per liter (mg/L) | Standard Deviation 33.2 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of Complement C4 | Week 6 (Pre-dose 12) | 121.3 Milligram per liter (mg/L) | Standard Deviation 41.5 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of Complement C4 | Week 6 (1 h post-dose 12) | 111.7 Milligram per liter (mg/L) | Standard Deviation 41.75 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of Complement C4 | Week 12 (Pre-dose 24) | 111.6 Milligram per liter (mg/L) | Standard Deviation 50.28 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of Complement C4 | Week 12 (1 h post-dose 24) | 90.7 Milligram per liter (mg/L) | Standard Deviation 27.72 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of Complement C4 | Week 12 (2 h post-dose 24) | 94.3 Milligram per liter (mg/L) | Standard Deviation 32.04 |
| Treatment B (1000 U CINRYZE) | Plasma Concentration of Complement C4 | Week 12 (4 h post-dose 24) | 103.7 Milligram per liter (mg/L) | Standard Deviation 32.35 |