Genetic Disorders, Hereditary Angioedema
Conditions
Brief summary
Hereditary angioedema (HAE) is a disease characterized by recurrent tissue swelling affecting various body locations. Recent literature shows that patients with frequent attacks may benefit from long-term prophylaxis. This study aims to evaluate the safety and prophylactic effect of weekly administrations of 50 IU/kg recombinant C1 Inhibitor (rhC1INH).
Interventions
50 IU/kg rhC1INH, IV injection over 4 to 5 minutes, once weekly over an 8-week treatment period.
Sponsors
Pharming Technologies B.V.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged at least 18 years * Signed informed consent * Comfirmed diagnosis of HAE with baseline plasma level of functional C1INH activity of less than 50% of normal, and/or proven HAE ,mutation in C1INH gene.
Exclusion criteria
* A history of anaphylaxis or severe allergy (i.e. requiring medication) to food, proteins and/or drugs. * A history of allergic reactions to C1INH products or rabbit protein. * Any reported SAE related to study drug administration (withdrawal criterium) * Elevated IgE against rabbit dander (\>0.35 kU/L; ImmunoCap assay; Phadia) * A diagnosis of acquired C1INH deficiency. * Woman of child bearing potential, pregnancy or breast-feeding * previous treatment within the last 3 months with plasma-derived C1INH * Any clinically significant abnormality in the routine haematology, biochemistry and urinalysis * Any condition or treatment that in the opinion of the investigator might interfere with the evaluation of the study objectives. * Any changes since screening that would exclude subject based on above
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HAE Attacks/Week | 8 weeks | Prior to the treatment period, patients enrolled in the study, were asked about the amount of HAE attacks in the past 2 years, (calculated to attacks/week), this number is defined as Historical. During the treatment period, patients received a dose of 50 IU/kg of rhC1INH administered by slow IV injection over 4 to 5 minutes, once a week during an eight week period. The amount of attacks during this period is defined as Prophylaxis (calculated to attacks/week). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Evaluation of Pharmacokinetic/ Pharmacodynamic (PK/PD)Parameters. | 8 weeks | PK/PD parameters will be based on concentration time curves after the 1st and 8th rhC1INH administration.(ratio visit 8/ visit 1, based on the area under the curve from baseline up to 4 hours after administration (AUC 0-4) |
Countries
Netherlands, Romania
Participant flow
Recruitment details
Patients with a history of frequent attacks, defined as HAE attacks occurring at least every two weeks were included in the study.
Participants by arm
| Arm | Count |
|---|---|
| Recombinant Human C1 Inhibitor Weekly administration of 50 IU/kg recombinant human C1 inhibitor
Recombinant Human C1 Inhibitor : 50 IU/kg rhC1INH, IV injection over 4 to 5 minutes, once weekly over an 8-week treatment period. | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | Recombinant Human C1 Inhibitor |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 25 |
| serious Total, serious adverse events | 2 / 25 |
Outcome results
Primary
HAE Attacks/Week
Prior to the treatment period, patients enrolled in the study, were asked about the amount of HAE attacks in the past 2 years, (calculated to attacks/week), this number is defined as Historical. During the treatment period, patients received a dose of 50 IU/kg of rhC1INH administered by slow IV injection over 4 to 5 minutes, once a week during an eight week period. The amount of attacks during this period is defined as Prophylaxis (calculated to attacks/week).
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Recombinant Human C1 Inhibitor | HAE Attacks/Week | Historical | 0.9 attacks/week |
| Recombinant Human C1 Inhibitor | HAE Attacks/Week | Prophylaxis | 0.4 attacks/week |
Secondary
The Evaluation of Pharmacokinetic/ Pharmacodynamic (PK/PD)Parameters.
PK/PD parameters will be based on concentration time curves after the 1st and 8th rhC1INH administration.(ratio visit 8/ visit 1, based on the area under the curve from baseline up to 4 hours after administration (AUC 0-4)
Time frame: 8 weeks
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Recombinant Human C1 Inhibitor | The Evaluation of Pharmacokinetic/ Pharmacodynamic (PK/PD)Parameters. | Functional C1 Inhibitor level | 1.06 ratio |
| Recombinant Human C1 Inhibitor | The Evaluation of Pharmacokinetic/ Pharmacodynamic (PK/PD)Parameters. | Antigenic C1 Inhibitor level | 1.02 ratio |
| Recombinant Human C1 Inhibitor | The Evaluation of Pharmacokinetic/ Pharmacodynamic (PK/PD)Parameters. | C4 level | 1.00 ratio |