Hereditary Angioedema
Conditions
Keywords
Hereditary Angioedema, HAE, Angioedema, Recombinant C1 Inhibitor, rhC1INH, Pediatrics
Brief summary
This open-label study is being conducted to confirm the safety, pharmacokinetic profile and efficacy of Ruconest at a dose of 50 U/kg when used for the treatment of acute angioedema attacks in patients, from 2 up to and including 13 years of age.
Detailed description
This study was an open-label, Phase 2, non-comparative, multinational, multicenter clinical study in pediatric patients from 2 up to and including 13 years of age, with a confirmed diagnosis of HAE. Patients were eligible for treatment with recombinant human C1-inhibitor (rhC1INH) if they presented to the clinic within 5 hours of onset with an acute attack of at least moderate severity without signs of spontaneous regression. Patients received rhC1INH at a dose of 50 U/kg body weight up to a maximum of 4200 U. The reconstituted solution was administered as a slow intravenous (iv) injection over approximately 5 minutes. The patients remained in hospital and were closely monitored in the study center for at least 4 hours after study medication administration.
Interventions
DRUGrhC1INH
Patients up to 84 kg will receive one i.v. injection of Ruconest at a dose of 50 U/kg. The reconstituted solution should be administered as a slow i.v. injection over approximately 5 minutes. Patients of 84 kg body weight or greater will receive one i.v. injection of Ruconest at the dose of 4200 U (2 vials).
Sponsors
Pharming Technologies B.V.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 13 Years
Healthy volunteers
No
Inclusion criteria
* From 2 up to and including 13 years of age * Clinical and laboratory confirmed diagnosis of HAE (baseline C1INH activity \<50% of normal) * Signed written Informed Consent Form (ICF)(parental permission) signed by the legal guardian(s) * Clinical symptoms of an acute HAE attack * Onset of eligible symptoms within 5 hours from the moment at which medical evaluation to determine eligibility has occurred * Attack severity moderate or greater, as rated by the investigator
Exclusion criteria
* A diagnosis of acquired C1INH deficiency (AAE) * A medical history of allergy to rabbits or rabbit-derived products or positive anti-rabbit epithelium (dander) immunoglobuline E (IgE) test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Beginning of Relief Based on Visual Analogue Scale (VAS) Was Defined as the Time, in Minutes, From Time of Infusion to the Beginning of Relief. | The assessment of the angioedema signs by the VAS and TEQ will be performed just before start of infusion, and at T30m, T1h, T2h, T4h, T8h and T24h after study medication infusion VAS score decrease of ≥ 20 mm from baseline. | Time to beginning of relief of symptoms that showed the response to treatment based on the overall VAS score decrease of ≥ 20 mm from baseline. Separate VAS forms will be given to express the current feelings considering the severity of angioedema symptoms for five possible anatomical locations. The form will be completed by placing vertical marks on each of the 100 mm horizontal lines. The Abdominal VAS measures the patient's perceptions relating to illness, pain, bloodedness, and nausea; the oro-pharyngeal-laryngeal (OPL) VAS measures illness, pain, swelling, breathing, speech, and swallowing; the facial VAS instrument measure illness, pain and swelling; the Peripheral VAS measures swelling, pain, and use of extremity; and the Urogenital VAS measures illness, pain, swelling, nausea, and urination. Time to beginning of relief will also be calculated based on the Investigator Score (IS) and Treatment Effect Questionnaire (TEQ). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Minimal Symptoms Based on Patient's VAS Scores; Time From the Start of the Infusion of Study Medication to the First Assessment Time at Which the Overall Severity VAS Reaches a Value of Less Than 20 mm for All Locations | The assessment of the angioedema signs by the VAS and TEQ will be performed just before start of infusion, and at T30m, T1h, T2h, T4h, T8h and T24h after study medication infusion all locations where VAS Scores were recorded. | Time to minimal symptoms was defined as the time at which the Overall VAS score fell below 20 mm for all locations where VAS Scores were recorded. Separate VAS forms will be given to express the current feelings considering the severity of angioedema symptoms for five possible anatomical locations. The form will be completed by placing vertical marks on each of the 100 mm horizontal lines provided to answer each question related to the severity of symptoms and the patient's condition. The Abdominal VAS measures the patient's perceptions relating to illness, pain, bloodedness, and nausea; the OPL VAS measures illness, pain, swelling, breathing, speech, and swallowing; the facial VAS instrument measure illness, pain and swelling; the Peripheral VAS measures swelling, pain, and use of extremity; and the Urogenital VAS measures illness, pain, swelling, nausea, and urination. |
Countries
Czechia, Germany, Hungary, Israel, Italy, North Macedonia, Poland, Romania, Slovakia, United States
Participant flow
Recruitment details
Male and female patients, from 2 up to and including 13 years of age with a clinically suspected and/or confirmed diagnosis of HAE will be recruited for this study. Patients will be identified and invited to participate by the investigators at the respective study centers.
Pre-assignment details
Screening details: Pts with a med hist of HAE (age 2-13 yrs) were invited for a screening visit. At screening the diagnosis HAE was confirmed via Central lab testing. If the diagnosis was confirmed, pts were eligible for treatment if an acute attack would occur and they presented to study center within 5 hrs of onset of attack. In total 57 pts signed ICF and 20 pts had one or more HAE attacks treated.
Participants by arm
| Arm | Count |
|---|---|
| Recombinant Human C1 Inhibitor Patients presented to the clinic within 5 hours of onset received rhC1INH 50 U/kg body weight up to a maximum of 4200 U.
rhC1INH: Patients up to 84 kg will receive one i.v. injection of Ruconest at a dose of 50 U/kg. The reconstituted solution should be administered as a slow i.v. injection over approximately 5 minutes. Patients of 84 kg body weight or greater will receive one i.v. injection of Ruconest at the dose of 4200 U (2 vials). | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study continued until at least 20 patients had been treated for at least one treatment. | 37 |
Baseline characteristics
| Characteristic | Recombinant Human C1 Inhibitor |
|---|---|
| Age, Categorical <=18 years | 20 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 9.55 years STANDARD_DEVIATION 3.304 |
| Height at screening | 125.6 centimeters STANDARD_DEVIATION 25.78 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Region of Enrollment Czechia | 2 participants |
| Region of Enrollment Germany | 1 participants |
| Region of Enrollment Hungary | 1 participants |
| Region of Enrollment Israel | 9 participants |
| Region of Enrollment North Macedonia | 2 participants |
| Region of Enrollment Poland | 2 participants |
| Region of Enrollment Romania | 2 participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 11 Participants |
| Weight at presentation | 34.81 kilograms STANDARD_DEVIATION 20.554 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 11 / 20 |
| serious Total, serious adverse events | 3 / 20 |
Outcome results
Primary
Time to Beginning of Relief Based on Visual Analogue Scale (VAS) Was Defined as the Time, in Minutes, From Time of Infusion to the Beginning of Relief.
Time to beginning of relief of symptoms that showed the response to treatment based on the overall VAS score decrease of ≥ 20 mm from baseline. Separate VAS forms will be given to express the current feelings considering the severity of angioedema symptoms for five possible anatomical locations. The form will be completed by placing vertical marks on each of the 100 mm horizontal lines. The Abdominal VAS measures the patient's perceptions relating to illness, pain, bloodedness, and nausea; the oro-pharyngeal-laryngeal (OPL) VAS measures illness, pain, swelling, breathing, speech, and swallowing; the facial VAS instrument measure illness, pain and swelling; the Peripheral VAS measures swelling, pain, and use of extremity; and the Urogenital VAS measures illness, pain, swelling, nausea, and urination. Time to beginning of relief will also be calculated based on the Investigator Score (IS) and Treatment Effect Questionnaire (TEQ).
Time frame: The assessment of the angioedema signs by the VAS and TEQ will be performed just before start of infusion, and at T30m, T1h, T2h, T4h, T8h and T24h after study medication infusion VAS score decrease of ≥ 20 mm from baseline.
Population: No statistical analyses have been specified for this primary end point. As this was an open-label single arm study, no statistical analyses could be provided.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Recombinant Human C1 Inhibitor | Time to Beginning of Relief Based on Visual Analogue Scale (VAS) Was Defined as the Time, in Minutes, From Time of Infusion to the Beginning of Relief. | 60 minutes |
Secondary
Time to Minimal Symptoms Based on Patient's VAS Scores; Time From the Start of the Infusion of Study Medication to the First Assessment Time at Which the Overall Severity VAS Reaches a Value of Less Than 20 mm for All Locations
Time to minimal symptoms was defined as the time at which the Overall VAS score fell below 20 mm for all locations where VAS Scores were recorded. Separate VAS forms will be given to express the current feelings considering the severity of angioedema symptoms for five possible anatomical locations. The form will be completed by placing vertical marks on each of the 100 mm horizontal lines provided to answer each question related to the severity of symptoms and the patient's condition. The Abdominal VAS measures the patient's perceptions relating to illness, pain, bloodedness, and nausea; the OPL VAS measures illness, pain, swelling, breathing, speech, and swallowing; the facial VAS instrument measure illness, pain and swelling; the Peripheral VAS measures swelling, pain, and use of extremity; and the Urogenital VAS measures illness, pain, swelling, nausea, and urination.
Time frame: The assessment of the angioedema signs by the VAS and TEQ will be performed just before start of infusion, and at T30m, T1h, T2h, T4h, T8h and T24h after study medication infusion all locations where VAS Scores were recorded.
Population: No statistical analyses for this end point
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Recombinant Human C1 Inhibitor | Time to Minimal Symptoms Based on Patient's VAS Scores; Time From the Start of the Infusion of Study Medication to the First Assessment Time at Which the Overall Severity VAS Reaches a Value of Less Than 20 mm for All Locations | 122.5 minutes |