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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-000987-92 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Recombinant Human C1 Inhibitor | Experimental | Patients presented to the clinic within 5 hours of onset received rhC1INH 50 U/kg body weight up to a maximum of 4200 U. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rhC1INH | Drug | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Anurag Relan, MD | VP Clinical Research & Medical Affairs at Pharming | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Portland Clinical Research/AAIM Care, LLC | Portland | Oregon | 97015 | United States | ||
| UIA FN Plzen ( Institute of Immunology and Allergology), Faculty Hospital Plzen |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30993784 | Result | Reshef A, Grivcheva-Panovska V, Kessel A, Kivity S, Klimaszewska-Rembiasz M, Moldovan D, Farkas H, Gutova V, Fritz S, Relan A, Giannetti B, Magerl M. Recombinant human C1 esterase inhibitor treatment for hereditary angioedema attacks in children. Pediatr Allergy Immunol. 2019 Aug;30(5):562-568. doi: 10.1111/pai.13065. Epub 2019 May 29. |
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | 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. | Posted | Median | 95% Confidence Interval | minutes | 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. |
Investigators are required to document all AEs occurring during the clinical study, commencing with the signing of the ICF through the last follow-up visit (Day 90 after the last treatment).
The reported values are based on the treatment-emergent (serious) adverse events (TE(S)AE), which are the (S)AEs with an onset at any time between the start of treatment and 97 days after treatment for any treated attack. The AEs are only analyzed for the 20 treated patients. The TLFs are based on these 20 treated and analyzed patients. A total of 11 patients experienced 30 TEAEs after treatment with rhC1INH. A total of 3 patients experienced 9 TESAEs after treatment with rhC1INH.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphocyte morphology abnormal | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Anurag Relan, MD, VP Clinical Research & Medical Affairs | Pharming Technologies BV | +31 715247400 | a.relan@pharming.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 10, 2014 | Sep 15, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 17, 2017 | Sep 15, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D054179 | Angioedemas, Hereditary |
| D000799 | Angioedema |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000081208 | Hereditary Complement Deficiency Diseases |
| D000081207 | Primary Immunodeficiency Diseases |
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| ID | Term |
|---|---|
| C571093 | conestat alfa |
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|
|
| 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. |
| Pilsen |
| Alej Svobody 80 |
| 304 60 Plzen |
| Czechia |
| University Hospital Motol, Institute of Immunology | Prague | V Úvalu 84 | 150 06 Prague | Czechia |
| Charité - Universitätsmedizin Berlin | Berlin | Charitéplatz 1 | 10117 | Germany |
| Klinikum Rechts der Isar, Technical University Munich | Munich | Germany |
| Heim Pál Gyermekkórház, II. számú Gyermek Belgyógyászati Osztály | Budapest | Madarász Utca 22-24 | 1131 | Hungary |
| Bnei Zion Hospital | Haifa | Israel |
| Souraski Medical Center | Tel Aviv | Israel |
| Sheba Medical Center | Tel Litwinsky | Israel |
| Hospital Luigi Sacco | Milan | Italy |
| Azienda Ospedaliera Universitaria S. Giovanni di Dio e Ruggi d'Aragona | Salerno | 84131 | Italy |
| University Clinic Of Dermatology Skopje | Skopje | 1000 | North Macedonia |
| Pediatric Hospital | Krakow | Poland |
| Pediatric Hospital | Lublin | Poland |
| Mures County Clinical Hospital | Târgu Mureş | Romania |
| Klinika detà a dorastu, Univerzitna nemocnica Martin | Martin | Kollárova 2 | 036 59 Martin | Slovakia |
| Participants |
| No |
|
| Age, Continuous | Median | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Height at screening | Mean | Standard Deviation | centimeters |
|
| Weight at presentation | Mean | Standard Deviation | kilograms |
|
|
|
|
| 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. | No statistical analyses for this end point | Posted | Median | 95% Confidence Interval | minutes | 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. |
|
|
|
| 0 |
| 20 |
| 3 |
| 20 |
| 11 |
| 20 |
| Pharyngeal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Eye swelling | Eye disorders | MedDRA 20.0 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Pallor | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
|
| Body temperature increased | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
|
| Catarrh | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Pharyngeal oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Eye swelling | Eye disorders | MedDRA 20.0 | Systematic Assessment |
|
| Middle ear effusion | Ear and labyrinth disorders | MedDRA 20.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Pharyngitis streptococcal | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Pharyngotonsillitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Feeling cold | General disorders | MedDRA 20.0 | Systematic Assessment |
|
| Peripheral swelling | General disorders | MedDRA 20.0 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
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| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D007153 | Immunologic Deficiency Syndromes |