Hereditary AngioedemaPhase 2NCT01359969
Safety of Ruconest in 2-13 Year Old Hereditary Angioedema (HAE) Patients
A Phase 2 study testing rhC1INH in people with Hereditary Angioedema, run by Pharming Technologies B.V. at 16 sites in 10 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 13 years
- Conditions the study is for
- Hereditary Angioedema
- What is being tested?
- rhC1INH
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 16 sitesin 10 countries
- Study dates
- 17 Jan 2012to 17 Jul 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 13 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
16 sites in 10 countries.
16 sites in 10 countries
Israel3 sites
Bnei Zion Hospital
Haifa
Souraski Medical Center
Tel Aviv
Sheba Medical Center
Tel Litwinsky
Czechia2 sites
UIA FN Plzen ( Institute of Immunology and Allergology), Faculty Hospital Plzen
Pilsen, Alej Svobody 80, 304 60 Plzen
University Hospital Motol, Institute of Immunology
Prague, V Úvalu 84, 150 06 Prague
Germany2 sites
Charité - Universitätsmedizin Berlin
Berlin, Charitéplatz 1, 10117
Klinikum Rechts der Isar, Technical University Munich
Munich
Italy2 sites
Hospital Luigi Sacco
Milan
Azienda Ospedaliera Universitaria S. Giovanni di Dio e Ruggi d'Aragona
Salerno, 84131
United States1 site
Portland Clinical Research/AAIM Care, LLC
Portland, Oregon, 97015
Hungary1 site
Heim Pál Gyermekkórház, II. számú Gyermek Belgyógyászati Osztály
Budapest, Madarász Utca 22-24, 1131
North Macedonia1 site
University Clinic Of Dermatology Skopje
Skopje, 1000
Slovakia1 site
Klinika detí a dorastu, Univerzitna nemocnica Martin
Martin, Kollárova 2, 036 59 Martin
About this study
Official title: Open-label, Phase II, Single Arm Study to Evaluate the Safety, Immunogenicity, Pharmacokinetics and Efficacy of rhC1INH for the Treatment of Acute Attacks in Pediatric Patients With Hereditary Angioedema, From 2-13 Years of Age
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.
Read the 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.
- Conditions
- Hereditary Angioedema
- Being tested
- rhC1INH
- Keywords
- Hereditary Angioedema, HAE, Angioedema, Recombinant C1 Inhibitor, rhC1INH, Pediatrics
- Medical subject headings
- Angioedemas, Hereditary, Angioedema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rhC1INHDrug
Also called Ruconest
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: rhC1INH |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Secondary outcomes (1)
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2011 (estimated)
- Study start17 Jan 2012
- Primary completion17 Jul 2017
- Study completion17 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hereditary AngioedemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pharming Technologies B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Anurag Relan, MD, Study director, VP Clinical Research & Medical Affairs at Pharming
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01359969
- Sponsor's protocol ID
- C1 1209
- Other IDs
- 2011-000987-92
- Status last verified
- Mar 2024
- First submitted
- 19 May 2011
- Last updated
- 29 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 30993784
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Phase II, Single Arm Study to Evaluate the Safety, Immunogenicity, Pharmacokinetics and Efficacy of rhC1INH for the Treatment of Acute Attacks in Pediatric Patients With Hereditary Angioedema, From 2-13 Years of Age
- ClinicalTrials.gov ID
- NCT01359969
- Acronym / sponsor ID
- C1 1209
- Conditions
- Hereditary Angioedema
- Keywords
- Hereditary Angioedema, HAE, Angioedema, Recombinant C1 Inhibitor, rhC1INH, Pediatrics
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Pharming Technologies B.V.Industry (pharma, biotech, devices)
- Study start
- 17 Jan 2012 (actual)
- Primary completion
- 17 Jul 2017 (actual)
- Study completion
- 17 Jul 2017 (actual)
- First posted
- 25 May 2011 (estimated)
- Results
- Posted 29 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Recombinant Human C1 Inhibitor | Experimental | Drug: rhC1INHPatients presented to the clinic within 5 hours of onset received rhC1INH 50 U/kg body weight up to a maximum of 4200 U. |
Who may qualify
- Ages
- 2 to 13 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rhC1INHAlso: RuconestPatients 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). | Drug | Recombinant Human C1 Inhibitor |
Primary outcome
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 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.
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).
1 secondary outcome
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 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30993784Reshef 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anurag Relan, MD study director
VP Clinical Research & Medical Affairs at Pharming
16 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing rhC1INH in people with Hereditary Angioedema, run by Pharming Technologies B.V. at 16 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Israel, Czechia, Germany, Italy, Poland and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01359969, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2024.