Hereditary AngioedemaPhase 3NCT00262301
Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks in Patients With Hereditary Angioedema
A Phase 3 study testing recombinant human C1 inhibitor in people with Hereditary Angioedema and Angioneurotic Edema, run by Pharming Technologies B.V. at 2 sites in 2 countries.
Trial summary
Hereditary angioedema ("HAE") is a genetic disorder characterized by sudden recurrent attacks of local swelling (angioedema). These attacks are often painful and disabling, and, in some cases, life-threatening. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Hereditary Angioedema, Angioneurotic Edema, Genetic Disorders
- What is being tested?
- recombinant human C1 inhibitor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jun 2004to Oct 2009
- Phase
- Phase 3
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Clear clinical and laboratory diagnosis of HAE
- Baseline plasma level of functional C1INH of less than 50% of normal
- Evidence for exacerbation or development of a severe abdominal, oro-facial/ pharyngeal/ laryngeal, genito-urinary and/or peripheral HAE attack
Who cannot join
- Acquired angioedema
- Pregnancy or breastfeeding
- Participation in another clinical study within prior 3 months
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Netherlands1 site
For information on sites, please contact Pharming Medical Affairs Deparment
Leiden, 2300 AL
Romania1 site
Emergency County Hospital, Internal Medicin Clinica, Allergology-Immunology Department
Târgu Mureş, 541103
About this study
Official title: A Randomized, Placebo-controlled, Double-blind Phase III Study of the Efficacy and Safety of Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks in Patients With Hereditary Angioedema
Hereditary angioedema ("HAE") is a genetic disorder characterized by sudden recurrent attacks of local swelling (angioedema). These attacks are often painful and disabling, and, in some cases, life-threatening. "HAE" is caused by mutations in the "C1INH" gene that leads to a decrease in the blood level of functional "C1INH". This multi-center study was designed to assess the safety and tolerability, efficacy and pharmacodynamics/ pharmacokinetics of recombinant human C1 inhibitor ("rhC1INH") in the treatment of acute hereditary angioedema attacks.
Read the detailed description
A prospectively planned interim analysis will be performed on the double-blind data.
- Being tested
- recombinant human C1 inhibitor, Placebo
- Medical subject headings
- Angioedemas, Hereditary, Angioedema, Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant human C1 inhibitorDrug
Also called "rhC1INH", Ruconest, conestat alfa
IV
PlaceboDrug
Also called saline, physiological salt solution
IV
| Study group | Role | What they receive |
|---|---|---|
| 100 IU/kg "rhC1INH" | Experimental | 100 IU/kg recombinant human C1 inhibitor Receives: Drug: recombinant human C1 inhibitor |
| Saline | Placebo comparator | Saline solution Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Beginning of Relief of Symptoms
The time to beginning of relief of symptoms has been assessed by using a patient-reported visual analogue scale ("VAS") ranging from 0 mm (no symptoms at all) to 100 mm (extremely disabling). Time to beginning of relief of symptoms at the location that showed first "VAS" score decrease of at least 20 mm from baseline score (t= 0 min) to the next assessment time-point). Assessment time-points were taken on pre-scheduled time-points after drug administration: baseline (0 minutes), 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 48 hours. Time to beginning of relief has been calculated as median time, by using the exact time-points on which each assessment was performed.
Measured: up to 48 hours after study drug administration
Secondary outcomes (1)
Time to Minimal Symptoms
the time to minimal symptoms was the time to minimal symptoms for an attack, assessed using the Visual Analogue Scale ("VAS") score. Symptoms were said to be minimal when the "VAS" score at all locations was below 20 mm. Assessment time-points were: baseline (0 minutes), 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 48 hours. Time to minimal symptoms has been calculated by using the exact time-points on which each assessment was performed.
Measured: up to 48 hours after study drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2005 (estimated)
- Study startJun 2004
- Primary completionJul 2009
- Study completionOct 2009
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 (4)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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pharming Technologies B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jan Nuijens, MD, PhD, Study chair, Pharming Group N.V.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00262301
- Sponsor's protocol ID
- C1 1304-01
- Status last verified
- Sep 2012
- First submitted
- 1 Dec 2005
- Last updated
- 2 Oct 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Zuraw B, Cicardi M, Levy RJ, Nuijens JH, Relan A, Visscher S, Haase G, Kaufman L, Hack CE. Recombinant human C1-inhibitor for the treatment of acute angioedema attacks in patients with hereditary angioedema. J Allergy Clin Immunol. 2010 Oct;126(4):821-827.e14. doi: 10.1016/j.jaci.2010.07.021.
PubMed 20920772Moldovan D, Reshef A, Fabiani J, Kivity S, Toubi E, Shlesinger M, Triggiani M, Montinaro V, Cillari E, Realdi G, Cancian M, Visscher S, Zanichelli A, Relan A, Cicardi M. Efficacy and safety of recombinant human C1-inhibitor for the treatment of attacks of hereditary angioedema: European open-label extension study. Clin Exp Allergy. 2012 Jun;42(6):929-35. doi: 10.1111/j.1365-2222.2012.03984.x.
PubMed 22909164Riedl MA, Narsipur N, Jones D, Tachdjian R, Relan A, Kilvert H, Aiello E, Habimana K, Roskell N, Gough A, Harper JR, Li HH, Harrington A. Post Hoc Analysis of Recombinant C1 Inhibitor Clinical Data Using Contemporary Endpoints for Hereditary Angioedema. Adv Ther. 2026 Aug;43(8):3506-3520. doi: 10.1007/s12325-026-03625-0. Epub 2026 May 20.
PubMed 42159953Bernstein JA, Relan A, Harper JR, Riedl M. Sustained response of recombinant human C1 esterase inhibitor for acute treatment of hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2017 Apr;118(4):452-455. doi: 10.1016/j.anai.2017.01.029. Epub 2017 Mar 9.
PubMed 28284978
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-controlled, Double-blind Phase III Study of the Efficacy and Safety of Recombinant Human C1 Inhibitor for the Treatment of Acute Attacks in Patients With Hereditary Angioedema
- ClinicalTrials.gov ID
- NCT00262301
- Acronym / sponsor ID
- C1 1304-01
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Pharming Technologies B.V.Industry (pharma, biotech, devices)
- Study start
- Jun 2004
- Primary completion
- Jul 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 6 Dec 2005 (estimated)
- Results
- Posted 30 Aug 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hereditary angioedema ("HAE") is a genetic disorder characterized by sudden recurrent attacks of local swelling (angioedema). These attacks are often painful and disabling, and, in some cases, life-threatening. "HAE" is caused by mutations in the "C1INH" gene that leads to a decrease in the blood level of functional "C1INH". This multi-center study was designed to assess the safety and tolerability, efficacy and pharmacodynamics/ pharmacokinetics of recombinant human C1 inhibitor ("rhC1INH") in the treatment of acute hereditary angioedema attacks.
Detailed description
A prospectively planned interim analysis will be performed on the double-blind data.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 100 IU/kg "rhC1INH" | Experimental | Drug: recombinant human C1 inhibitor100 IU/kg recombinant human C1 inhibitor |
| Saline | Placebo comparator | Drug: PlaceboSaline solution |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Clear clinical and laboratory diagnosis of HAE
- Baseline plasma level of functional C1INH of less than 50% of normal
- Evidence for exacerbation or development of a severe abdominal, oro-facial/ pharyngeal/ laryngeal, genito-urinary and/or peripheral HAE attack
Key exclusion criteria (3 listed)
- Acquired angioedema
- Pregnancy or breastfeeding
- Participation in another clinical study within prior 3 months
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 |
|---|---|---|
| recombinant human C1 inhibitorAlso: "rhC1INH", Ruconest, conestat alfaIV | Drug | 100 IU/kg "rhC1INH" |
| PlaceboAlso: saline, physiological salt solutionIV | Drug | Saline |
Primary outcome
Time to Beginning of Relief of Symptoms
Time frame: up to 48 hours after study drug administration
The time to beginning of relief of symptoms has been assessed by using a patient-reported visual analogue scale ("VAS") ranging from 0 mm (no symptoms at all) to 100 mm (extremely disabling). Time to beginning of relief of symptoms at the location that showed first "VAS" score decrease of at least 20 mm from baseline score (t= 0 min) to the next assessment time-point). Assessment time-points were taken on pre-scheduled time-points after drug administration: baseline (0 minutes), 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours, 48 hours. Time to beginning of relief has been calculated as median time, by using the exact time-points on which each assessment was performed.
1 secondary outcome
Time to Minimal Symptoms
Time frame: up to 48 hours after study drug administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20920772Zuraw B, Cicardi M, Levy RJ, Nuijens JH, Relan A, Visscher S, Haase G, Kaufman L, Hack CE. Recombinant human C1-inhibitor for the treatment of acute angioedema attacks in patients with hereditary angioedema. J Allergy Clin Immunol. 2010 Oct;126(4):821-827.e14. doi: 10.1016/j.jaci.2010.07.021.
- Results publication: PubMed 22909164Moldovan D, Reshef A, Fabiani J, Kivity S, Toubi E, Shlesinger M, Triggiani M, Montinaro V, Cillari E, Realdi G, Cancian M, Visscher S, Zanichelli A, Relan A, Cicardi M. Efficacy and safety of recombinant human C1-inhibitor for the treatment of attacks of hereditary angioedema: European open-label extension study. Clin Exp Allergy. 2012 Jun;42(6):929-35. doi: 10.1111/j.1365-2222.2012.03984.x.
- Derived from this study: PubMed 42159953Riedl MA, Narsipur N, Jones D, Tachdjian R, Relan A, Kilvert H, Aiello E, Habimana K, Roskell N, Gough A, Harper JR, Li HH, Harrington A. Post Hoc Analysis of Recombinant C1 Inhibitor Clinical Data Using Contemporary Endpoints for Hereditary Angioedema. Adv Ther. 2026 Aug;43(8):3506-3520. doi: 10.1007/s12325-026-03625-0. Epub 2026 May 20.
- Derived from this study: PubMed 28284978Bernstein JA, Relan A, Harper JR, Riedl M. Sustained response of recombinant human C1 esterase inhibitor for acute treatment of hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2017 Apr;118(4):452-455. doi: 10.1016/j.anai.2017.01.029. Epub 2017 Mar 9.
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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.
Jan Nuijens, MD, PhD study chair
Pharming Group N.V.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing recombinant human C1 inhibitor in people with Hereditary Angioedema and Angioneurotic Edema, run by Pharming Technologies B.V. at 2 sites in 2 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 3 inclusion and 3 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 2 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands, Romania. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 30 Aug 2012). 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 of Symptoms (time frame: up to 48 hours after study drug administration). 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 NCT00262301, which also lists 4 linked publications.
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 2 Oct 2012.