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This study will evaluate the safety and efficacy of an oral treatment, BCX4161, in preventing acute attacks in participants with hereditary angioedema (HAE). Eligible participants will be randomized to receive one of two doses of BCX4161 or placebo for 12 weeks. The study will compare the number of acute attacks in each treatment group, as well as a number of other clinical outcomes, and the safety and tolerability of each dose of BCX4161 compared to placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BCX4161 300 mg three times daily | Experimental | Three BCX4161 capsules (100 mg) and two placebo capsules to be taken three times daily by mouth |
|
| BCX4161 500 mg three times daily | Experimental | Five BCX4161 capsules (100 mg) to be taken three times daily by mouth |
|
| Placebo three times daily | Placebo Comparator | Five placebo capsules to be taken three times daily by mouth |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BCX4161 | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| The Mean Acute Angioedema Attack Rate | An angioedema attack was defined as swelling at any location reported by participant, which had no swelling earlier. Total number of confirmed attacks during the treatment period standardized to a weekly attack-rate to adjust for the total duration of treatment. The attack rate was derived for each participant by treatment period. The weekly attack rate was equal to the total number of confirmed attacks during a treatment period divided by the duration of the treatment (in days) times 7 days. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Attack-free Days | The number of attack free days was the sum of the days during the treatment period for which participants reported no attacks. | 12 weeks |
| Number of Participants Who Are Attack-free |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marc Riedl, MD MS | UCSD | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Birmingham | Alabama | 35209 | United States | |||
| 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. |
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Participants were recruited from study sites in Belgium, Canada, France, Germany, Hungary, Italy, the United Kingdom and the United States, between December 2014 and October 2015
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| ID | Title | Description |
|---|---|---|
| FG000 | BCX4161 300 mg three times daily | Three BCX4161 capsules (100 mg) and two placebo capsules to be taken three times daily by mouth BCX4161 Placebo |
| FG001 | BCX4161 500 mg three times daily |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Drug |
|
The number of participants who reported no attacks during the 12-week treatment period.
| 12 weeks |
| Disease Activity, as Measured by the 84-day Angioedema Activity Score | Angioedema Activity Score (AAS) consists of 5 questions (period in which swelling occurred, physical discomfort, daily activity restriction, cosmetic disfigurement, and overall severity) to be answered for each day during which a subject experiences an HAE attack. A score between 0 (no symptoms) and 3 (Severe symptoms) was assigned to the responses for each question and the total daily score will be derived as the sum of the 5 question scores for each day during which the subject experiences a confirmed attack. Daily AAS ranged from 0 to 15 with higher scores indicating the greater disease severity. For participants who completed the study, the 84-day AAS was obtained by sum of AAS score during the treatment period and ranged from 0 (best) to 1,260 (worst).For participants who discontinued the study prematurely the 84-day AAS was obtained using the formula: Sum of AAS score of each day on treatment ∗ 84/Number of days on treatment. | 12 weeks |
| Change From Baseline at Week 12, in Quality of Life as Measured by the Angioedema Quality of Life Questionnaire | Angioedema Quality of Life questionnaire (AE-QoL) consisted of 4 domains (i.e., functioning, fatigue/mood, fear/shame, and nutrition) and a total score based on a total of 17 possible responses. The results of all the responses are summed up and transformed to a scale ranging from 0 (best) to 100 (worst). | Baseline (Day 1) and Week 12 |
| Number of Participants With Treatment Emergent Adverse Events | An adverse event (AE) is any untoward medical occurrence in a clinical study participant. No causal relationship with study drug or with the clinical study itself is implied. An AE could be an unfavorable and unintended sign, symptom (including an abnormal laboratory finding), syndrome, or illness that developed or worsened during the clinical study. A serious adverse event (SAE) is any untoward medical occurrence resulting in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or other medically important event. Any graded abnormality that occurred following the initiation of study drug and up to 30 days after the last dose of study drug, and represented at least a 1-grade increase from the baseline assessment, was defined as treatment emergent. | From first dose up to 14 weeks |
| Change From Baseline at Week 12 in Quality of Life, as Measured by the EuroQoL Five-dimensional, 5-level Questionnaire | The EuroQoL five-dimensional, 5-level (EQ-5D-5L) was used to assess overall wellbeing and comprised the following five domains: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each domain has 5 response levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. It included the EQ Visual Analogue scale (EQ VAS) to rate overall health on a scale of 0 (worst health) to 100 (best health). | Baseline (Day 1) and Week 12 |
| Scottsdale |
| Arizona |
| 85251 |
| United States |
| Granada Hills | California | 91344 | United States |
| San Diego | California | 92093 | United States |
| San Diego | California | 92112 | United States |
| Walnut Creek | California | 94598 | United States |
| Colorado Springs | Colorado | 80907 | United States |
| Shreveport | Louisiana | 71106 | United States |
| Chevy Chase | Maryland | 20815 | United States |
| Boston | Massachusetts | 02114 | United States |
| Plymouth | Minnesota | 55446 | United States |
| St Louis | Missouri | 63141 | United States |
| New York | New York | 10029 | United States |
| Charlotte | North Carolina | 28277 | United States |
| Cincinnati | Ohio | 45267 | United States |
| Oklahoma City | Oklahoma | 73131 | United States |
| Tulsa | Oklahoma | 74133 | United States |
| Lake Oswego | Oregon | 97035 | United States |
| Hershey | Pennsylvania | 17033 | United States |
| Pittsburgh | Pennsylvania | 15241 | United States |
| Dallas | Texas | 75231 | United States |
| Galveston | Texas | 77555 | United States |
| Fairfax | Virginia | 63141 | United States |
| Spokane | Washington | 99204 | United States |
| Tacoma | Washington | 98405 | United States |
| Leuven | Belgium |
| Ottawa | Canada |
| Grenoble | France |
| Lille | France |
| Paris | France |
| Berlin | Germany |
| Frankfurt | Germany |
| Mörfelden-Walldorf | Germany |
| Budapest | Hungary |
| Milan | Italy |
| Birmingham | United Kingdom |
| Bristol | United Kingdom |
| Cardiff | United Kingdom |
| London | United Kingdom |
| Manchester | United Kingdom |
Five BCX4161 capsules (100 mg) to be taken three times daily by mouth
BCX4161
| FG002 | Placebo three times daily | Five placebo capsules to be taken three times daily by mouth Placebo |
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | BCX4161 300 mg Three Times Daily | Three BCX4161 capsules (100 mg) and two placebo capsules to be taken three times daily by mouth BCX4161 Placebo |
| BG001 | BCX4161 500 mg Three Times Daily | Five BCX4161 capsules (100 mg) to be taken three times daily by mouth BCX4161 |
| BG002 | Placebo Three Times Daily | Five placebo capsules to be taken three times daily by mouth Placebo |
| BG003 | 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, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
| ||||||||||||||||
| Qualifying attack rate | The study qualifying attack rate is based on run-in period attack rate or historical attack rate where historical attack data was not available. Run-in Attack Rate = Total Number of attacks reported during run - in period ∗ 7/ Duration of run-in period in days. Duration of run-in period is the date of the last qualifying attack - date of screening+1 and is reported in days. Historical Attack Rate =Total Number of Historical attacks reported ∗ 7/ Duration of historical reporting period in days. An HAE attack defined by pink rings on the skin/erythema marginatum. | Mean | Standard Deviation | Attacks/ week |
|
| 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 | The Mean Acute Angioedema Attack Rate | An angioedema attack was defined as swelling at any location reported by participant, which had no swelling earlier. Total number of confirmed attacks during the treatment period standardized to a weekly attack-rate to adjust for the total duration of treatment. The attack rate was derived for each participant by treatment period. The weekly attack rate was equal to the total number of confirmed attacks during a treatment period divided by the duration of the treatment (in days) times 7 days. | The intent-to-treat (ITT) population included all participants who were randomized and received at least 1 dose of study intervention. | Posted | Least Squares Mean | Standard Error | Confirmed attacks per week | 12 weeks |
|
|
| |||||||||||||||||||||||||||||||
| Secondary | Number of Attack-free Days | The number of attack free days was the sum of the days during the treatment period for which participants reported no attacks. | The ITT population included all participants who were randomized and received at least 1 dose of study intervention. | Posted | Mean | Standard Deviation | Number of attack-free days | 12 weeks |
|
| ||||||||||||||||||||||||||||||||
| Secondary | Number of Participants Who Are Attack-free | The number of participants who reported no attacks during the 12-week treatment period. | The ITT population included all participants who were randomized and received at least 1 dose of study intervention. | Posted | Count of Participants | Participants | 12 weeks |
|
| |||||||||||||||||||||||||||||||||
| Secondary | Disease Activity, as Measured by the 84-day Angioedema Activity Score | Angioedema Activity Score (AAS) consists of 5 questions (period in which swelling occurred, physical discomfort, daily activity restriction, cosmetic disfigurement, and overall severity) to be answered for each day during which a subject experiences an HAE attack. A score between 0 (no symptoms) and 3 (Severe symptoms) was assigned to the responses for each question and the total daily score will be derived as the sum of the 5 question scores for each day during which the subject experiences a confirmed attack. Daily AAS ranged from 0 to 15 with higher scores indicating the greater disease severity. For participants who completed the study, the 84-day AAS was obtained by sum of AAS score during the treatment period and ranged from 0 (best) to 1,260 (worst).For participants who discontinued the study prematurely the 84-day AAS was obtained using the formula: Sum of AAS score of each day on treatment ∗ 84/Number of days on treatment. | The ITT population included all participants who were randomized and received at least 1 dose of study intervention. | Posted | Mean | Standard Deviation | score on a scale | 12 weeks |
| |||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline at Week 12, in Quality of Life as Measured by the Angioedema Quality of Life Questionnaire | Angioedema Quality of Life questionnaire (AE-QoL) consisted of 4 domains (i.e., functioning, fatigue/mood, fear/shame, and nutrition) and a total score based on a total of 17 possible responses. The results of all the responses are summed up and transformed to a scale ranging from 0 (best) to 100 (worst). | The ITT population included all participants who were randomized and received at least 1 dose of study intervention. Here 'Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline (Day 1) and Week 12 |
| |||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Treatment Emergent Adverse Events | An adverse event (AE) is any untoward medical occurrence in a clinical study participant. No causal relationship with study drug or with the clinical study itself is implied. An AE could be an unfavorable and unintended sign, symptom (including an abnormal laboratory finding), syndrome, or illness that developed or worsened during the clinical study. A serious adverse event (SAE) is any untoward medical occurrence resulting in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, or other medically important event. Any graded abnormality that occurred following the initiation of study drug and up to 30 days after the last dose of study drug, and represented at least a 1-grade increase from the baseline assessment, was defined as treatment emergent. | The safety population included all randomized participants who received at least 1 dose of study intervention. | Posted | Count of Participants | Participants | From first dose up to 14 weeks |
| ||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline at Week 12 in Quality of Life, as Measured by the EuroQoL Five-dimensional, 5-level Questionnaire | The EuroQoL five-dimensional, 5-level (EQ-5D-5L) was used to assess overall wellbeing and comprised the following five domains: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each domain has 5 response levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. It included the EQ Visual Analogue scale (EQ VAS) to rate overall health on a scale of 0 (worst health) to 100 (best health). | The ITT population included all participants who were randomized and received at least 1 dose of study intervention. Here 'Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline (Day 1) and Week 12 |
|
From first dose up to 14 weeks.
The safety population included all randomized participants who received at least 1 dose of study intervention.
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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 | BCX4161 300 mg three times daily | Three BCX4161 capsules (100 mg) and two placebo capsules to be taken three times daily by mouth BCX4161 Placebo | 0 | 36 | 2 | 36 | 31 | 36 |
| EG001 | BCX4161 500 mg three times daily | Five BCX4161 capsules (100 mg) to be taken three times daily by mouth BCX4161 | 0 | 38 | 3 | 38 | 35 | 38 |
| EG002 | Placebo three times daily | Five placebo capsules to be taken three times daily by mouth Placebo | 0 | 36 | 3 | 36 | 32 | 36 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hereditary angioedema | Congenital, familial and genetic disorders | MedDRA Version 18.1 | Systematic Assessment | HAE attack requiring hospitalization |
|
| Chest discomfort | General disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Abortion induced | Surgical and medical procedures | MedDRA Version 18.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal distension | Gastrointestinal disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Faeces soft | Gastrointestinal disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Frequent bowel movements | Gastrointestinal disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Hereditary angioedema | Congenital, familial and genetic disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA Version 18.1 | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA Version 18.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA Version 18.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA Version 18.1 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA Version 18.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA Version 18.1 | Systematic Assessment |
| |
| Tonsilitis | Infections and infestations | MedDRA Version 18.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA Version 18.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA Version 18.1 | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA Version 18.1 | Systematic Assessment |
| |
| Vulvovaginal candidiasis | Infections and infestations | MedDRA Version 18.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA Version 18.1 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA Version 18.1 | Systematic Assessment |
| |
| Blood urine present | Investigations | MedDRA Version 18.1 | Systematic Assessment |
| |
| GGT increased | Investigations | MedDRA Version 18.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Ovarian cyst | Reproductive system and breast disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA Version 18.1 | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA Version 18.1 | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| VP Clinical Development | BioCryst Pharmaceuticals, Inc | (+1) 919 859 1302 | clinicaltrials@biocryst.com |
| ID | Term |
|---|---|
| D054179 | Angioedemas, Hereditary |
| ID | Term |
|---|---|
| D000799 | Angioedema |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000081208 | Hereditary Complement Deficiency Diseases |
| D000081207 | Primary Immunodeficiency Diseases |
| 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 |
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| ID | Term |
|---|---|
| C000722673 | avoralstat |
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| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Hungary |
|
| Belgium |
|
| United States |
|
| Italy |
|
| United Kingdom |
|
| France |
|
| Germany |
|
|
|
| OG002 | Placebo three times daily | Five placebo capsules to be taken three times daily by mouth Placebo |
|
|
|
|
| OG002 | Placebo three times daily | Five placebo capsules to be taken three times daily by mouth Placebo |
|
|
Five placebo capsules to be taken three times daily by mouth
Placebo
|
|