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C1 esterase inhibitor · 6 trials · 2 indications
Subjects were to assess their symptoms every 15 minutes up to 4 hours after the initial dose or until substantial relief of the defining symptom was achieved. The conservative analysis defined substantial relief as 3 consecutive assessments of improvement of the defining symptom; any attack that did not have 3 consecutive documented reports of improvement was considered a treatment failure. In the less conservative analysis, attacks also were considered to have responded if clinical improvement of the defining symptom occurred but data were incomplete due to cessation of symptom assessments.
A hereditary angioedema (HAE) attack was defined as a discrete episode during which the subject progressed from no angioedema to symptoms of angioedema.
Randomized subjects assessed their symptoms every 15 minutes up to 4 hours after the initial dose of blinded study drug or until substantial relief of the defining symptom was achieved. Substantial relief was defined as 3 consecutive assessments of improvement of the defining symptom. Beginning of substantial relief was considered the first of the 3 consecutive assessments.
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 protocol-specified Day 20 (post-treatment) biopsy was compared to the qualifying biopsy to assess changes in histopathology for light and immunofluorescence microscopy. The Central Pathologist provided the following categorical information from the qualifying biopsy in an AMR Scorecard: C4d Score (0-100), Margination Score (0-100) Glomerulitis Score (0-100), Vasculitis Score (0-100), Glomerulosclerosis Score (0-100), Chronic Glomerulopathy Score (0-100), Interstitial Fibrosis Score (0-100), and the Chronic Vasculitis Score (0-100), with 0 being absence of abnormal histopathology. The "qualifying" renal allograft biopsy was performed as standard of care (SOC) within 12 months after transplant and prior to screening for this study. The first dose of study drug (Day 1) was administered within 72 hours after qualifying biopsy. A negative change from baseline indicates that histopathology has improved. Endpoint includes subjects with both Qualifying and Day 20 Biopsies.
| Arm | Type | Description |
|---|---|---|
| Open-label C1INH-nf | EXPERIMENTAL | 1,000 Units (U) of C1INH-nf administered intravenously. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered. |
| C1INH-nf | EXPERIMENTAL | 1,000 Units (U) of C1INH-nf administered intravenously (IV). If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered. |
| Placebo | PLACEBO_COMPARATOR | Matching placebo (saline) administered IV. If there was no response to treatment 60 minutes after the first dose, a second placebo (saline) dose could be administered. |
| 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. |
| C1 Esterase Inhibitor (Human) | EXPERIMENTAL | Subjects were to receive C1 esterase inhibitor intravenously at a rate of approximately 1 mL per minute as tolerated. Subjects were to receive a total of 7 doses over a 2-week period: an initial IV infusion of 5000 U (not to exceed 100 U/kg) on Day 1, followed by 2500 U (not to exceed 50 U/kg) IV on Days 3, 5, 7, 9, 11, and 13 |
| Normal Saline | PLACEBO_COMPARATOR | placebo infused as above |
| Single Dose | EXPERIMENTAL | 1,000 Units (U) of C1INH-nf administered intravenously (IV). |
| First Dose Followed by Second Dose | EXPERIMENTAL | 1,000 U of C1INH-nf administered IV, followed by a second 1,000 U dose 60 minutes later. |
| Name | Type | Description |
|---|---|---|
| C1 esterase inhibitor [human] (C1INH-nf) | BIOLOGICAL | - |
| Placebo (saline) | DRUG | - |
| Placebo | BIOLOGICAL | - |
| C1 Esterase Inhibitor (Human) | BIOLOGICAL | - |
Inclusion Criteria: This study was open to all subjects who: * Completed participation in LEVP2005-1/A (NCT00289211) and were not participating in LEVP2005-1/B (NCT01005888), any time after the 3-day telephone follow-up * Completed participation in LEVP2005-1/B any time after the final prophylacti...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Intellia Therapeutics, Inc. | NTLA | 3 | PHASE3 | NTLA-2002, Normal Saline Administration |
| BioCryst Pharmaceuticals, Inc. | BCRX | 2 | PHASE3 | Berotralstat |
| Ionis Pharmaceuticals, Inc. | IONS | 1 | PHASE3 | Donidalorsen |
| Pharvaris N.V. | PHVS | 1 | PHASE2 | deucrictibant |
| BioMarin Pharmaceutical Inc. | BMRN | 1 | PHASE1 | Dose 1 of BMN 331 |
| Astria Therapeutics, Inc. | ATXS | 1 | PHASE2 | STAR-0215 |
C1 Esterase Inhibitor is used for Hereditary Angioedema and Graft Rejection. It is being developed by Takeda Pharmaceutical Company Limited (TAK) and is currently in Phase 2 clinical development for these indications. The drug is a monoclonal antibody being studied in the immunology therapeutic area.
C1 Esterase Inhibitor is being developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. The company is conducting clinical trials to evaluate the drug for Hereditary Angioedema and Graft Rejection. The drug is currently in Phase 2 development.
C1 Esterase Inhibitor is in Phase 2 clinical development. It is being studied for Hereditary Angioedema and Graft Rejection. The drug is investigational and has not been approved by regulatory authorities. Takeda Pharmaceutical Company Limited (TAK) is the developer.
C1 Esterase Inhibitor has completed five clinical trials with a total enrollment of 395 participants. Key trials include NCT00432510, a Phase 1 pharmacokinetic study in Hereditary Angioedema, and NCT00438815, NCT00462709, and NCT01005888, which are Phase 3 studies for treating or preventing acute Hereditary Angioedema attacks. All trials were conducted in the United States.
C1 Esterase Inhibitor is not FDA approved. It is an investigational drug currently in Phase 2 clinical development for Hereditary Angioedema and Graft Rejection. The developer, Takeda Pharmaceutical Company Limited (TAK), has completed five clinical trials but the drug remains under investigation.
C1 Esterase Inhibitor is a monoclonal antibody that targets the C1 esterase enzyme. By inhibiting this enzyme, the drug aims to regulate the complement system and reduce inflammation. It is being studied for its potential to treat Hereditary Angioedema and Graft Rejection.