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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-001054-42 | EudraCT Number |
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The aim of this study is to assess the long-term safety of C1-esterase inhibitor (C1-INH) in preventing hereditary angioedema (HAE) attacks when it is administered under the skin of subjects with HAE. The safety of participating subjects will be assessed for up to 54 weeks. The long-term efficacy of C1-INH will also be assessed. Each eligible subject will enter the treatment phase, wherein subjects will be randomized to treatment with either low- or medium-volume C1-INH. Subjects who have an insufficient treatment response during the study will be given an opportunity to undergo a dose increase. The study aims to enroll eligible subjects who completed study CSL830_3001 (NCT01912456). Subjects who did not participate in study CSL830_3001 may also participate, if eligible and if space permits. Subjects from the United States (US) who complete Treatment Period 2 will be allowed to participate in an Extension Period. During the Extension Period participating US subjects will continue to receive treatment with open-label CSL830 for up to an additional 88 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| C1-INH - low-volume dose | Experimental | A low-volume dose of C1-INH will be administered subcutaneously twice a week for up to 52 weeks (up to 146 weeks extension period). |
|
| C1-INH - medium-volume dose | Experimental | A medium-volume dose of C1-INH will be administered subcutaneously twice a week for up to 52 weeks (up to 146 weeks extension period). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| C1-esterase inhibitor | Biological |
|
| Measure | Description | Time Frame |
|---|---|---|
| Person-time Incidence Rates (Subject Based) | Subject-based Analysis for Person-Time Incidence Rate = (the total number of subjects who experienced the event during the respective treatment) / (the sum of the date each subject experienced the event - the subject's start date + 1 day) / (365.25 days). The analysis population for this endpoint was the Safety Population: the Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. | Up to 146 weeks. |
| The Person-time Incidence Rates (Event Based) | Event-based Analysis for Person-Time Incidence Rate = (the total number of events documented during the respective treatment) / (the sum of each subject's end date - the subject's start date + 1 day) / (365.25 days). The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. | Up to 146 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Subjects Who Have Solicited Adverse Events (AEs) | The number of subjects having at least 1 solicited local AE during a treatment were divided by the number of subjects in the corresponding treatment. The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Global Clinical Program Director | CSL Behring | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Study Site | Birmingham | Alabama | 35209 | United States | ||
| Study Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36326435 | Derived | Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K. Interventions for the long-term prevention of hereditary angioedema attacks. Cochrane Database Syst Rev. 2022 Nov 3;11(11):CD013403. doi: 10.1002/14651858.CD013403.pub2. | |
| 33588897 | Derived | Lumry WR, Zuraw B, Cicardi M, Craig T, Anderson J, Banerji A, Bernstein JA, Caballero T, Farkas H, Gower RG, Keith PK, Levy DS, Li HH, Magerl M, Manning M, Riedl MA, Lawo JP, Prusty S, Machnig T, Longhurst H; on behalf of the COMPACT Investigators. Long-term health-related quality of life in patients treated with subcutaneous C1-inhibitor replacement therapy for the prevention of hereditary angioedema attacks: findings from the COMPACT open-label extension study. Orphanet J Rare Dis. 2021 Feb 15;16(1):86. doi: 10.1186/s13023-020-01658-4. |
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| ID | Title | Description |
|---|---|---|
| FG000 | CSL830 (40) | A low-volume dose of C1-INH (40 IU/kg) administered subcutaneously twice a week |
| FG001 | CSL830 (60) | A high-volume dose of C1-INH (60 IU/kg) administered subcutaneously twice a week |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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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 | Jul 10, 2015 | Sep 18, 2018 |
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| Up to 146 weeks |
| Percentage of Injections Followed by At Least One Solicited Adverse Event | The percent of injections followed by at least one solicited adverse event. The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. This was assessed across all participants, calculated as total number of events following injections / total number of injections across all participants, in each Arm. | Up to 146 weeks |
| Percentage of Subjects Who Become Seropositive for Human Immunodeficiency Virus (HIV-1/-2), Hepatitis B Virus, or Hepatitis C Virus. | Blood samples to be tested for HIV-1/-2, HBV, and HCV. The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. | Up to 146 weeks |
| Percentage of Subjects Who Experience a Time-normalized HAE Attack Frequency of <1 HAE Attack Per 4-Week Period | The percentage of subjects with a time-normalized merged HAE attack frequency of <1 HAE attack per 4-week period. The analysis population for this endpoint was the Intent-to-Treat (ITT) Population: The ITT Population comprised all subjects who provided informed consent / assent and were randomized, regardless of whether or not they received CSL 830. | Up to 146 weeks |
| Percentage of Subjects Who Are Responders | A responder was defined as a subject with a ≥ 50% reduction in the time-normalized number of HAE attacks on CSL830 relative to the time-normalized number of HAE attacks used to qualify for participation in the current study. The analysis population for this endpoint was the Intent-to-Treat (ITT) Population: The ITT Population comprised all subjects who provided informed consent / assent and were randomized, regardless of whether or not they received CSL830. Not all subjects in the ITT were available for this outcome measure. | Up to 146 weeks |
| Scottsdale |
| Arizona |
| 85251 |
| United States |
| Study Site | La Jolla | California | 92037 | United States |
| Study Site | Orange | California | 92868 | United States |
| Study Site | Walnut Creek | California | 94598 | United States |
| Study Site | Chevy Chase | Maryland | 20815 | United States |
| Study Site | Cincinnati | Ohio | 45231 | United States |
| Study Site | Tulsa | Oklahoma | 74136 | United States |
| Study Site | Portland | Oregon | 97223 | United States |
| Study Site | Hershey | Pennsylvania | 17033 | United States |
| Study Site | Dallas | Texas | 75231 | United States |
| Study Site | Richmond | Virginia | 23298 | United States |
| Study Site | Campbelltown | New South Wales | 2560 | Australia |
| Study Site | Hamilton | Ontario | L8N 3Z5 | Canada |
| Study Site | Ottawa | Ontario | K1Y 4G2 | Canada |
| Study Site | Toronto | Ontario | M4V 1R2 | Canada |
| Study Site | Québec | G1V 4M6 | Canada |
| Study Site | Pilsen | 30460 | Czechia |
| Study Site | Mörfelden-Walldorf | Hesse | 64546 | Germany |
| Study Site | Berlin | 10117 | Germany |
| Study Site | Frankfurt | 60596 | Germany |
| Study Site | Mainz | 55131 | Germany |
| Study Site | Budapest | 1125 | Hungary |
| Study Site | Tel Aviv | 64239 | Israel |
| Study Site | Tel Litwinsky | 52621 | Israel |
| Study Site | Catania | 95123 | Italy |
| Study Site | Milan | 20157 | Italy |
| Study Site | Cluj-Napoca | 400139 | Romania |
| Study Site | Madrid | 28007 | Spain |
| Study Site | Madrid | 28046 | Spain |
| Study Site | Valencia | 46026 | Spain |
| Study Site | London | E1 2ES | United Kingdom |
| 32042283 | Derived | Levy DS, Farkas H, Riedl MA, Hsu FI, Brooks JP, Cicardi M, Feuersenger H, Pragst I, Reshef A. Long-term efficacy and safety of subcutaneous C1-inhibitor in women with hereditary angioedema: subgroup analysis from an open-label extension of a phase 3 trial. Allergy Asthma Clin Immunol. 2020 Feb 4;16:8. doi: 10.1186/s13223-020-0409-3. eCollection 2020. |
| 30772477 | Derived | Craig T, Zuraw B, Longhurst H, Cicardi M, Bork K, Grattan C, Katelaris C, Sussman G, Keith PK, Yang W, Hebert J, Hanzlikova J, Staubach-Renz P, Martinez-Saguer I, Magerl M, Aygoren-Pursun E, Farkas H, Reshef A, Kivity S, Neri S, Crisan I, Caballero T, Baeza ML, Hernandez MD, Li H, Lumry W, Bernstein JA, Hussain I, Anderson J, Schwartz LB, Jacobs J, Manning M, Levy D, Riedl M, Christiansen S, Feuersenger H, Pragst I, Mycroft S, Pawaskar D, Jacobs I; COMPACT Investigators. Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks. J Allergy Clin Immunol Pract. 2019 Jul-Aug;7(6):1793-1802.e2. doi: 10.1016/j.jaip.2019.01.054. Epub 2019 Feb 15. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | CSL830 (40) | A low-volume dose of C1-INH (40 IU/kg) administered subcutaneously twice a week |
| BG001 | CSL830 (60) | A high-volume dose of C1-INH (60 IU/kg) administered subcutaneously twice a week |
| BG002 | Total | Total of all reporting groups |
| 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 | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | 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 | Person-time Incidence Rates (Subject Based) | Subject-based Analysis for Person-Time Incidence Rate = (the total number of subjects who experienced the event during the respective treatment) / (the sum of the date each subject experienced the event - the subject's start date + 1 day) / (365.25 days). The analysis population for this endpoint was the Safety Population: the Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. | Safety population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. | Posted | Number | participants with events/year | Up to 146 weeks. |
|
|
| ||||||||||||||||||||||||||||||||||||
| Primary | The Person-time Incidence Rates (Event Based) | Event-based Analysis for Person-Time Incidence Rate = (the total number of events documented during the respective treatment) / (the sum of each subject's end date - the subject's start date + 1 day) / (365.25 days). The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. | Safety population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. | Posted | Number | events/year | Up to 146 weeks. |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Subjects Who Have Solicited Adverse Events (AEs) | The number of subjects having at least 1 solicited local AE during a treatment were divided by the number of subjects in the corresponding treatment. The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. | Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. | Posted | Number | Percent of subjects | Up to 146 weeks |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Injections Followed by At Least One Solicited Adverse Event | The percent of injections followed by at least one solicited adverse event. The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. This was assessed across all participants, calculated as total number of events following injections / total number of injections across all participants, in each Arm. | Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. | Posted | Number | Percent of injections | Up to 146 weeks |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Subjects Who Become Seropositive for Human Immunodeficiency Virus (HIV-1/-2), Hepatitis B Virus, or Hepatitis C Virus. | Blood samples to be tested for HIV-1/-2, HBV, and HCV. The analysis population for this endpoint was the Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. | Safety Population: The Safety Population comprised all subjects who provided informed consent / assent, who were randomized, and who received at least 1 dose or a partial dose of CSL830. | Posted | Number | Percent of Subjects | Up to 146 weeks |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Subjects Who Experience a Time-normalized HAE Attack Frequency of <1 HAE Attack Per 4-Week Period | The percentage of subjects with a time-normalized merged HAE attack frequency of <1 HAE attack per 4-week period. The analysis population for this endpoint was the Intent-to-Treat (ITT) Population: The ITT Population comprised all subjects who provided informed consent / assent and were randomized, regardless of whether or not they received CSL 830. | Intent-to-Treat (ITT) Population: The ITT Population comprised all subjects who provided informed consent / assent and were randomized, regardless of whether or not they received CSL 830. | Posted | Number | Percent of Subjects | Up to 146 weeks |
|
| |||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Subjects Who Are Responders | A responder was defined as a subject with a ≥ 50% reduction in the time-normalized number of HAE attacks on CSL830 relative to the time-normalized number of HAE attacks used to qualify for participation in the current study. The analysis population for this endpoint was the Intent-to-Treat (ITT) Population: The ITT Population comprised all subjects who provided informed consent / assent and were randomized, regardless of whether or not they received CSL830. Not all subjects in the ITT were available for this outcome measure. | Intent-to-Treat (ITT) Population: The ITT Population comprised all subjects who provided informed consent / assent and were randomized, regardless of whether or not they received CSL830. | Posted | Number | 95% Confidence Interval | Percent of Subjects | Up to 146 weeks |
|
|
146 weeks per subject
n=70 because 7 subjects titrated up from the 40 IU/kg arm and will be displayed in both arms.
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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 | CSL830 (40) | A low-volume dose of C1-INH (40 IU/kg) administered subcutaneously twice a week | 0 | 63 | 4 | 63 | 33 | 63 |
| EG001 | CSL830 (60) | A high-volume dose of C1-INH (60 IU/kg) administered subcutaneously twice a week | 0 | 70 | 5 | 70 | 28 | 70 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Contusion | Injury, poisoning and procedural complications | MedDRA (18.0) | Systematic Assessment |
| |
| Diffuse large B-cell lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (18.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Diplopia | Eye disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Contusion | Injury, poisoning and procedural complications | MedDRA (18.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Injection site erythema | General disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Injection site bruising | General disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Injection site reaction | General disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Injection site haematoma | General disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Injection site induration | General disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Injection site swelling | General disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (18.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (18.0) | Systematic Assessment |
|
None reported
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michelle Hellstern | CSL Behring | 6102907515 | michelle.hellstern@cslbehring.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 12, 2017 | Sep 18, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D056829 | Hereditary Angioedema Types I and II |
| ID | Term |
|---|---|
| D054179 | Angioedemas, Hereditary |
| D000799 | Angioedema |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D050718 | Complement C1 Inhibitor Protein |
| ID | Term |
|---|---|
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D003174 | Complement C1 Inactivator Proteins |
| 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 |
Not provided
Not provided
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Romania |
|
| Hungary |
|
| United States |
|
| Czechia |
|
| Italy |
|
| United Kingdom |
|
| Israel |
|
| Australia |
|
| Germany |
|
| Spain |
|
| Anaphylaxis |
|
| HAE Attacks Resulting in In-Patient Hospitalizatio |
|
| Solicited AEs Graded as Severe |
|
| Related SAEs Other Than Specified Above |
|
| Antibodies to C1-INH (Inhibitory + Non-inhibitory) |
|
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| Participants |
|
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