Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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 lead to a decrease in the blood level of functional "C1INH". This multi-center study was designed to assess the safety and tolerability, efficacy, and pharmacokinetics/pharmacodynamics of recombinant human C1 inhibitor ("rhC1INH") in the treatment of acute hereditary angioedema attacks.
Funding Source - FDA OOPD
A prospectively planned interim analysis will be performed on the double-blind data.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 100 IU/kg rhC1INH | Experimental | 100 IU/kg Recombinant human C1 inhibitor |
|
| 50 IU/kg rhC1INH | Experimental | 50 IU/kg Recombinant human C1 inhibitor |
|
| Saline | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Recombinant Human C1 Inhibitor | Drug | IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Beginning of Relief of Symptoms | The time to beginning of relief of symptoms at the location that showed the first visual analogue scale ("VAS") score decrease of at least 20 mm from baseline score with persistence to the next timepoint, assessment timepoints were taken on pre-scheduled time-points after study drug administration: baseline (0 minutes), 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours and 48 hours. Time to beginning of relief has been calculated as median time, by using the exact timepoints on which each assessment was performed. | up to 48 hours after study drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| 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 timepoints were: baseline, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours and 48 hours. Time to minimal symtoms has been calculated by using the exact timepoints on which each assessment was performed. |
Not provided
Main Inclusion Criteria:
Main Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Anurag Relan, MD | Pharming Group N.V. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| For information on sites please contact Pharming Medical Affairs Department | Leiden | 2300 AL | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20920772 | Result | 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. | |
| 42159953 | Derived |
Not provided
Not provided
Patients could be enrolled into the open-label phase of the study after treatment in the double-blind phase of the study, including those enrolled but not treated in the double-blind phase.
During the double-blind phase of the study, patients were randomized once to receive 100 IU/kg "rhC1INH", 50 IU/kg "rhC1INH" or Saline in a ratio of 1:1:1. After treatment in the double-blind phase, patients with subsequent eligible attacks could be treated with open-label 50 IU/kg "rhC1INH".
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 100 IU/kg "rhC1INH" | Includes all subjects randomized and treated with 100 IU/kg Recombinant human C1 inhibitor in the double-blind phase |
| FG001 | 50 IU/kg "rhC1INH" | Includes all subjects randomized and treated with 50 IU/kg Recombinant human C1 inhibitor in the double-blind phase |
| FG002 | Placebo | Includes all subjects randomized and treated with Placebo in the double-blind phase |
| FG003 | 50 IU/kg Open-label "rhC1INH" | Includes all subjects treated with 50 IU/kg open-label "rhC1INH" in the open-label phase. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Double-blind Phase |
| |||||||||||||
| Open-label Phase |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 100 IU/kg "rhC1INH" | Baseline characteristics were calculated for the modified intention to treat ("mITT") and per protocol analysis populations, which included all subjects who received 100 IU/kg "rhC1INH". |
| BG001 | 50 IU/kg "rhC1INH" |
| 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 of Symptoms | The time to beginning of relief of symptoms at the location that showed the first visual analogue scale ("VAS") score decrease of at least 20 mm from baseline score with persistence to the next timepoint, assessment timepoints were taken on pre-scheduled time-points after study drug administration: baseline (0 minutes), 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours and 48 hours. Time to beginning of relief has been calculated as median time, by using the exact timepoints on which each assessment was performed. | The full analysis set ("FAS" or "mITT") was defined as the set of patients who provided Informed Consent, were randomized and took at least one dose of the study drug administration. | Posted | Median | Full Range | minutes | up to 48 hours after study drug administration |
|
Treatment-Emergent-Adverse-Events (TEAEs) were defined as events with start from onset of study drug administration. Serious Adverse events and Adverse events for each arm with onset dates within 7 days of study drug administration have been listed.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 100 IU/kg rhC1INH | Includes all subjects receiving 100 IU/kg Recombinant human C1 inhibitor |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| pneumonia - severe | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| back pain | Musculoskeletal and connective tissue disorders | MedDRA (9.1) | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Affairs Department | Pharming Technologies BV | +31715247400 | medicalinfo@pharming.com |
| ID | Term |
|---|---|
| D054179 | Angioedemas, Hereditary |
| D000799 | Angioedema |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000081208 | Hereditary Complement Deficiency Diseases |
| D000081207 | Primary Immunodeficiency Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D050718 | Complement C1 Inhibitor Protein |
| C571093 | conestat alfa |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D003174 | Complement C1 Inactivator Proteins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| placebo | Drug | saline solution |
|
|
| up to 48 hours after study drug administration |
| Riedl 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 May 20. doi: 10.1007/s12325-026-03625-0. Online ahead of print. |
| 28284978 | Derived | Bernstein 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. |
| 23535096 | Derived | Riedl MA, Levy RJ, Suez D, Lockey RF, Baker JW, Relan A, Zuraw BL. Efficacy and safety of recombinant C1 inhibitor for the treatment of hereditary angioedema attacks: a North American open-label study. Ann Allergy Asthma Immunol. 2013 Apr;110(4):295-9. doi: 10.1016/j.anai.2013.02.007. Epub 2013 Mar 6. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Baseline characteristics were calculated for the modified intention to treat ("mITT") and per protocol analysis populations, which included subjects who received 50 IU/kg "rhC1INH". One (1) subject was randomized to the 50 IU/kg "rhC1INH" arm, but did not receive study drug administration and was excluded from the "mITT" analysis population. |
| BG002 | Placebo | Baseline characteristics were calculated for the modified intention to treat ("mITT") analysis population, which included all subjects randomized to the placebo arm. |
| BG003 | 50 IU/kg Open-label "rhC1INH" | Baseline characteristics were calculated for the modified intention to treat ("mITT")analysis population, which included all subjects who received 50 IU/kg open-label "rhC1INH". |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
Includes all subjects enrolled and randomized to the 100 IU/kg body weight recombinant human C1 Inhibitor arm
| OG001 | 50 IU/kg "rhC1INH" | Includes all subjects enrolled and randomized to the 50 IU/kg body weight recombinant human C1 Inhibitor arm |
| OG002 | Placebo | Includes all subjects enrolled and randomized to the Saline arm |
| OG003 | 50 IU/kg Open-label "rhC1INH" | Includes all subjects who received 50 IU/kg open-label Recombinant human C1 inhibitor |
|
|
|
| Secondary | 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 timepoints were: baseline, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, 24 hours and 48 hours. Time to minimal symtoms has been calculated by using the exact timepoints on which each assessment was performed. | The full analysis set ("FAS" or "mITT") was defined as the set of patients who provided Informed Consent, were randomized and took at least one dose of the study drug administration. | Posted | Median | Full Range | minutes | up to 48 hours after study drug administration |
|
|
|
|
| 0 |
| 13 |
| 2 |
| 13 |
| EG001 | 50 IU/kg rhC1INH | Includes all subjects receiving 50 IU/kg Recombinant human C1 inhibitor | 0 | 12 | 2 | 12 |
| EG002 | Placebo | Includes all subjects receiving Saline solution | 0 | 13 | 3 | 13 |
| EG003 | 50 IU/kg Open-label "rhC1INH" | Includes all subjects receiving 50 IU/kg open-label recombinant human C1 inhibitor and subjects receiving an additional dose of 50 IU/kg "rhC1INH" within 4 hours after initial administration. | 4 | 62 | 18 | 62 |
| escherichia sepsis | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
| vertigo - severe | Nervous system disorders | MedDRA (9.1) | Systematic Assessment |
|
| hypersensitivity | Immune system disorders | MedDRA (9.1) | Systematic Assessment |
|
| headache | Nervous system disorders | MedDRA (9.1) | Systematic Assessment |
|
| injection site swelling | General disorders | MedDRA (9.1) | Systematic Assessment |
|
| myalgia | Musculoskeletal and connective tissue disorders | MedDRA (9.1) | Systematic Assessment |
|
| rash erythematous | Skin and subcutaneous tissue disorders | MedDRA (9.1) | Systematic Assessment |
|
| throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| vertigo | Nervous system disorders | MedDRA (9.1) | Systematic Assessment |
|
| diarrhea | Gastrointestinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| nausea | Gastrointestinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| erythema | Skin and subcutaneous tissue disorders | MedDRA (9.1) | Systematic Assessment |
|
| sinusitis | Respiratory, thoracic and mediastinal disorders | MedDRA (9.1) | Systematic Assessment |
|
| fatigue | General disorders | MedDRA (9.1) | Systematic Assessment |
|
| urinary tract infection | Infections and infestations | MedDRA (9.1) | Systematic Assessment |
|
The investigator must provide a copy of any results communication to the sponsor for review at least 30 days prior to its submission or disclosure. The sponsor may request to delete information identified by sponsor as confidential information prior to submitting such manuscript and/or abstract for publication. For a multi-center study, the investigator must wait (i) at least 24 months after the study is completed at all sites or (ii) until after the multi-center publication.
| 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 |
| D015843 |
| Serpins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D003169 | Complement Inactivator Proteins |
| D003165 | Complement System Proteins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
| 95 |
| No |
| Superiority or Other |