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
The study objective was to determine the safety and efficacy of C1INH-nf for the prevention of acute HAE attacks.
Subjects were given diary cards and instructed to document all HAE attacks on a daily basis. Subjects evaluated their symptoms over the previous 24 hours, noting the severity and duration of swelling at each of 5 locations (abdominal, genitourinary, facial, respiratory [including laryngeal], and/or extremity).
The study design also allowed for administration of open-label C1INH-nf (1,000 U of C1INH-nf administered IV [repeated after 60 minutes, if necessary] for treatment of laryngeal angioedema or if deemed necessary by the investigator; 1,000 U of C1INH-nf administered IV [single dose] prior to emergency surgical procedures).
A total of 26 subjects were enrolled in the study. One subject received open-label C1INH-nf but withdrew prior to randomization. Another subject was randomized but withdrew prior to receiving study drug. Twenty-four (24) subjects were randomized and treated with blinded study drug. In total, 25 subjects received at least 1 dose of study drug and were analyzed for safety; all 25 subjects were exposed to C1INH-nf and 23 subjects were exposed to placebo.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| C1INH-nf First, then Placebo | Experimental | 1,000 Units (U) of C1INH-nf administered intravenously (IV) every 3 to 4 days (approximately twice weekly) for 12 weeks, followed by matching placebo (saline) administered IV every 3 to 4 days for 12 weeks. |
|
| Placebo First, then C1INH-nf | Experimental | Matching placebo (saline) administered IV every 3 to 4 days (approximately twice weekly) for 12 weeks, followed by 1,000 U of C1INH-nf administered IV every 3 to 4 days for 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| C1 esterase inhibitor [human] (C1INH-nf) | Biological |
| ||
| Measure | Description | Time Frame |
|---|---|---|
| Number of Hereditary Angioedema (HAE) Attacks During Each Prophylactic Therapy Period | An HAE attack was defined as the subject-reported indication of swelling at any location following a report of no swelling on the previous day. Analyses include observed attack counts and normalized attack counts (i.e., the number of attacks observed during each therapy period, normalized for the number of days the subject participated in that period). | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subject Withdrawals During Each Prophylactic Therapy Period | At the end of each therapy period, each subject was assigned a yes/no drop-out status. A drop-out was defined as a subject who did not have a Week 12 visit record. | 12 weeks |
| Average Severity of HAE Attacks During Each Prophylactic Therapy Period |
| Measure | Description | Time Frame |
|---|---|---|
| Total Number of Days of Swelling During Each Prophylactic Therapy Period | A day of swelling was defined as a day that a subject reported swelling at any of the five locations (abdominal, genitourinary, facial, respiratory [including laryngeal], or extremity). | 12 weeks |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Allergy and Immunology Associates | Scottsdale | Arizona | 85251 | United States | ||
| University of California, San Diego |
| 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. | |
| 25295804 | Derived | Lumry WR, Miller DP, Newcomer S, Fitts D, Dayno J. Quality of life in patients with hereditary angioedema receiving therapy for routine prevention of attacks. Allergy Asthma Proc. 2014 Sep-Oct;35(5):371-6. doi: 10.2500/aap.2014.35.3783. |
Not provided
Not provided
A total of 26 subjects were enrolled in the study (see Detailed Description). One subject received open-label C1 esterase inhibitor (C1INH-nf) but withdrew prior to randomization. Another subject was randomized but withdrew prior to receiving study drug. 24 subjects were randomized and began therapy with blinded study drug in Period 1.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | C1INH-nf First, Then Placebo | 1,000 Units (U) of C1INH-nf administered intravenously (IV) every 3 to 4 days (approximately twice weekly) for 12 weeks, followed by matching placebo (saline) administered IV every 3 to 4 days for 12 weeks. |
| FG001 | Placebo First, Then C1INH-nf |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| First Intervention |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo (saline) |
| Drug |
|
All attacks in each therapy period were assigned a value of 1 (mild), 2 (moderate), or 3 (severe). Attack severity was considered the highest value assigned by the subject to any swelling location during the attack. Average severity was set to 0 if there was no attack in a period. |
| 12 weeks |
| Average Duration of HAE Attacks During Each Prophylactic Therapy Period | The duration of an attack was measured from the first report of swelling at any one of the five locations (abdominal, genitourinary, facial, respiratory [including laryngeal], or extremity) until the first subsequent report of "no swelling" at all five locations. | 12 weeks |
| Number of Open-label C1INH-nf Infusions Required During Each Prophylactic Therapy Period | The study design allowed for subjects to be treated with open-label C1INH-nf for laryngeal angioedema, if deemed necessary by the investigator, or prior to emergency surgical procedures. | 12 weeks |
| Antigenic C1 Inhibitor (C1INH) Serum Levels | Change in antigenic C1INH serum levels from pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12. Pre-infusion samples obtained at Visit 1 of each therapy period (i.e., baseline) were used to determine change at 1 hour post-infusion for all visits. | Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12 |
| Functional C1INH Serum Levels | Percent change in functional C1INH serum levels from pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12. Pre-infusion samples obtained at Visit 1 of each therapy period (i.e., baseline) were used to determine change at 1 hour post-infusion for all visits. Functional C1INH serum levels are expressed as a percent of total detectable C1INH (i.e., functional C1INH/total detectable C1INH). | Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12 |
| San Diego |
| California |
| 92093-0732 |
| United States |
| Allergy and Asthma Clinical Research, Inc | Walnut Creek | California | 94598 | United States |
| Atlanta Allergy and Asthma Clinic | Suwanee | Georgia | 30024 | United States |
| Hawaii Pacific Health Research Institute | Honolulu | Hawaii | 96826 | United States |
| Welborn Clinic Allergy and Immunology | Evansville | Indiana | 47713 | United States |
| Lake Charles Memorial Hospital | Lake Charles | Louisiana | 70601 | United States |
| Institute for Asthma and Allergy | Wheaton | Maryland | 20902 | United States |
| Libby Clinic | Libby | Montana | 59923 | United States |
| Mount Sinai School of Medicine | New York | New York | 10029 | United States |
| Nationwide Childrens Hospital Clinical Research | Columbus | Ohio | 43205 | United States |
| Allergy Clinic of Tulsa | Tulsa | Oklahoma | 74133 | United States |
| Allergy Asthma and Dermatology Research Center | Lake Oswego | Oregon | 97035 | United States |
| AARA Research Center | Dallas | Texas | 75231 | United States |
| Tyler County Hospital | Woodville | Texas | 75979 | United States |
| St. Joseph's Hospital/Cornerstone Healthcare | Parkersburg | West Virginia | 26101 | United States |
| 23312695 | Derived | Lumry W, Manning ME, Hurewitz DS, Davis-Lorton M, Fitts D, Kalfus IN, Uknis ME. Nanofiltered C1-esterase inhibitor for the acute management and prevention of hereditary angioedema attacks due to C1-inhibitor deficiency in children. J Pediatr. 2013 May;162(5):1017-22.e1-2. doi: 10.1016/j.jpeds.2012.11.030. Epub 2013 Jan 11. |
| 20818886 | Derived | Zuraw BL, Busse PJ, White M, Jacobs J, Lumry W, Baker J, Craig T, Grant JA, Hurewitz D, Bielory L, Cartwright WE, Koleilat M, Ryan W, Schaefer O, Manning M, Patel P, Bernstein JA, Friedman RA, Wilkinson R, Tanner D, Kohler G, Gunther G, Levy R, McClellan J, Redhead J, Guss D, Heyman E, Blumenstein BA, Kalfus I, Frank MM. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. 2010 Aug 5;363(6):513-22. doi: 10.1056/NEJMoa0805538. |
Matching placebo (saline) administered IV every 3 to 4 days (approximately twice weekly) for 12 weeks, followed by 1,000 U of C1INH-nf administered IV every 3 to 4 days for 12 weeks. |
| COMPLETED |
|
| NOT COMPLETED |
|
| Second Intervention |
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | C1INH-nf First, Then Placebo | 1,000 U of C1INH-nf administered IV every 3 to 4 days (approximately twice weekly) for 12 weeks, followed by matching placebo (saline) administered IV every 3 to 4 days for 12 weeks. |
| BG001 | Placebo First, Then C1INH-nf | Matching placebo (saline) administered IV every 3 to 4 days (approximately twice weekly) for 12 weeks, followed by 1,000 U of C1INH-nf administered IV every 3 to 4 days for 12 weeks. |
| BG002 | Open-label C1INH-nf Only | One subject received open-label C1INH-nf but withdrew prior to randomization. |
| BG003 | Randomized, Not Treated | One subject was randomized but withdrew prior to receiving study drug. |
| BG004 | 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 |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | 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 | Number of Hereditary Angioedema (HAE) Attacks During Each Prophylactic Therapy Period | An HAE attack was defined as the subject-reported indication of swelling at any location following a report of no swelling on the previous day. Analyses include observed attack counts and normalized attack counts (i.e., the number of attacks observed during each therapy period, normalized for the number of days the subject participated in that period). | The Efficacy Dataset (N=22) consisted of all randomized subjects who completed 12 weeks of therapy in Period 1 and received at least one infusion of study drug in Period 2. | Posted | Mean | Standard Deviation | attacks | 12 weeks |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Subject Withdrawals During Each Prophylactic Therapy Period | At the end of each therapy period, each subject was assigned a yes/no drop-out status. A drop-out was defined as a subject who did not have a Week 12 visit record. | The Safety Dataset (N=24) consisted of all randomized subjects who received at least 1 complete or partial infusion of study drug. 24 subjects began Period 1 (12 C1INH-nf, 12 placebo) and received study drug. 22 subjects crossed over to Period 2 (11 placebo, 11 C1INH-nf) and received study drug. Thus, 23 randomized subjects received each therapy. | Posted | Number | participants | 12 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Average Severity of HAE Attacks During Each Prophylactic Therapy Period | All attacks in each therapy period were assigned a value of 1 (mild), 2 (moderate), or 3 (severe). Attack severity was considered the highest value assigned by the subject to any swelling location during the attack. Average severity was set to 0 if there was no attack in a period. | Efficacy Dataset. | Posted | Mean | Standard Deviation | units on a scale | 12 weeks |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Average Duration of HAE Attacks During Each Prophylactic Therapy Period | The duration of an attack was measured from the first report of swelling at any one of the five locations (abdominal, genitourinary, facial, respiratory [including laryngeal], or extremity) until the first subsequent report of "no swelling" at all five locations. | Efficacy Dataset. | Posted | Mean | Standard Deviation | days | 12 weeks |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Open-label C1INH-nf Infusions Required During Each Prophylactic Therapy Period | The study design allowed for subjects to be treated with open-label C1INH-nf for laryngeal angioedema, if deemed necessary by the investigator, or prior to emergency surgical procedures. | Efficacy Dataset. | Posted | Mean | Standard Deviation | infusions | 12 weeks |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Total Number of Days of Swelling During Each Prophylactic Therapy Period | A day of swelling was defined as a day that a subject reported swelling at any of the five locations (abdominal, genitourinary, facial, respiratory [including laryngeal], or extremity). | Efficacy Dataset. | Posted | Mean | Standard Deviation | days | 12 weeks |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Antigenic C1 Inhibitor (C1INH) Serum Levels | Change in antigenic C1INH serum levels from pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12. Pre-infusion samples obtained at Visit 1 of each therapy period (i.e., baseline) were used to determine change at 1 hour post-infusion for all visits. | Efficacy Dataset subjects with data at both sampling time points (N=19 C1INH-nf, N=22 placebo). | Posted | Mean | Standard Deviation | mg/dL | Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Functional C1INH Serum Levels | Percent change in functional C1INH serum levels from pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12. Pre-infusion samples obtained at Visit 1 of each therapy period (i.e., baseline) were used to determine change at 1 hour post-infusion for all visits. Functional C1INH serum levels are expressed as a percent of total detectable C1INH (i.e., functional C1INH/total detectable C1INH). | Efficacy Dataset subjects with data at both sampling time points (N=20 C1INH-nf, N=22 placebo). | Posted | Mean | Standard Deviation | percent of functional C1INH | Pre-infusion to 1 hour post-infusion at Visit 1 and Weeks 4, 8, and 12 |
|
|
Up to 6 months (i.e., 24 weeks) of therapy and 3 months of follow-up. 25 subjects received at least 1 dose of study drug and were analyzed for safety; all 25 were exposed to C1INH-nf and 23 were exposed to placebo (see Detailed Description).
Presented are treatment-emergent adverse reactions considered to be related to study drug. There were no serious adverse reactions considered related to study drug.
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 | C1INH-nf | 0 | 25 | 3 | 25 | |||
| EG001 | Placebo | 0 | 23 | 0 | 23 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (9.0) |
| ||
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (9.0) |
| ||
| Rash | Skin and subcutaneous tissue disorders | MedDRA (9.0) |
| ||
| Chest discomfort | General disorders | MedDRA (9.0) |
| ||
| Pyrexia | General disorders | MedDRA (9.0) |
| ||
| Dizziness | Nervous system disorders | MedDRA (9.0) |
| ||
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (9.0) |
|
Clinical Study Agreement. Most restrictive provision - PI will not publish results until after first of: multicenter publication is published or 24 months from study end. Thereafter, PI may publish his results. PI must provide copy of proposed publication to sponsor for pre-review. If sponsor requests, PI must delete sponsor confidential information before publication and/or delay publication for 90 days so sponsor can file for patents or take other action to protect its patent rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.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 |
Not provided
Not provided
| ID | Term |
|---|---|
| D050718 | Complement C1 Inhibitor Protein |
| D012965 | Sodium Chloride |
| 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 |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
Normalized number of attacks. |
| 95 |
| Superiority or Other (legacy) |
|
|
|
|
|
|
|
|
|
|
|
|
|
|