A Phase 3 interventional study of C1 esterase inhibitor [human] (C1INH-nf) in Hereditary Angioedema, sponsored by Shire. Completed at 30 sites in United States. Open to participants aged 1 Year and older. Per ClinicalTrials.gov, last updated 2021-06-08.
Sponsored by Shire · Phase 3, Interventional, and Treatment
The study objective was to evaluate the safety and efficacy of repeat use of C1INH-nf for the treatment of acute HAE attacks.
A total of 113 subjects were enrolled in the study. One-hundred-one (101) subjects received C1INH-nf for the treatment of 1 or more HAE attacks and were analyzed for efficacy. The study design also allowed for short-term prophylaxis with C1INH-nf prior to emergency or non-cosmetic surgical or dental procedures, and an additional 12 subjects received C1INH-nf only for this purpose. All 113 subjects were exposed to C1INH-nf and analyzed for safety.
164 studies on the registry are indexed under Angioedema; 19 are open to participants now.
This study's enrollment of 113 is above the median of 44 across 111 interventional studies indexed under Angioedema.
Browse Angioedema studies →Shire is the lead sponsor of 346 studies on the registry; 2 are open to participants now.
Of its 47 completed or terminated interventional studies of FDA-regulated products, 47 (100%) have results posted.
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This study was open to all subjects who:
Were excluded from LEVP2005-1 for any of the following reasons:
Were not enrolled in LEVP2005-1 after enrollment in LEVP2005-1 was closed, under the following circumstances:
Exclusion Criteria:
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.
Biological: C1 esterase inhibitor [human] (C1INH-nf)
Number of Hereditary Angioedema (HAE) Attacks Treated With C1INH-nf
Time frame: Duration of the study (2.5 years)
Percent of HAE Attacks With Substantial Relief of the Defining Symptom
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.
Time frame: Within 4 hours after initial treatment
Time to Beginning of Substantial Relief of the Defining Symptom
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. 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.
Time frame: Within 4 hours after initial treatment
Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments
For attack number 1, the number of censored observations precluded estimation of the 95% confidence interval (CI) upper bound for median time to event (subjects who did not experience beginning of substantial relief of the defining symptom within 4 hours after initial treatment were included in the analysis as censored observations). Entry of 4.0 hours indicates that data were not estimable (NE); as non-numeric data are not supported by the 95% CI field, entry of the actual result (ie, NE or \>4.0) was not possible.
Time frame: Within 4 hours after initial treatment
Antigenic C1 Inhibitor (C1INH) Serum Levels
Change in antigenic C1INH serum levels from pre-infusion to 1 hour after the initial dose of study drug.
Time frame: Pre-infusion to 1 hour post-infusion
Functional C1INH Serum Levels
Percent change in functional C1INH serum levels from pre-infusion to 1 hour after the initial dose of study drug. Functional C1INH serum levels are expressed as a percent of total detectable C1INH (ie, functional C1INH/total detectable C1INH).
Time frame: Pre-infusion to 1 hour post-infusion
Complement C4 Serum Levels
Change in complement C4 serum levels from pre-infusion to 1 hour after the initial dose of study drug.
Time frame: Pre-infusion to 1 hour post-infusion
| Milestone | Open-label C1INH-nf |
|---|---|
| Started | 113 |
| Completed | 43 |
| Not completed | 70 |
| Withdrew: Transferred to levp2006-4 (nct00462709) | 30 |
| Withdrew: 3-month follow-up no longer required | 12 |
| Withdrew: Noncompliance with protocol requirements | 9 |
| Withdrew: Transitioned to commercial c1inh-nf | 6 |
| Withdrew: Lost to follow-up | 6 |
| Withdrew: Withdrawal by subject | 6 |
| Withdrew: Death | 1 |
| attacks | Open-label C1INH-nf |
|---|---|
| Conservative Analysis | 609 |
| Less Conservative Analysis | 598 |
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. 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.
| hours | Open-label C1INH-nf |
|---|---|
| Time to Beginning of Substantial Relief of the Defining Symptom | 0.75 (0.50 to 1.00) |
For attack number 1, the number of censored observations precluded estimation of the 95% confidence interval (CI) upper bound for median time to event (subjects who did not experience beginning of substantial relief of the defining symptom within 4 hours after initial treatment were included in the analysis as censored observations). Entry of 4.0 hours indicates that data were not estimable (NE); as non-numeric data are not supported by the 95% CI field, entry of the actual result (ie, NE or \>4.0) was not possible.
| hours | Open-label C1INH-nf |
|---|---|
| Attack number 1 | 1.50 (0.75 to 4.00) |
| Attack number 2 | 0.50 (0.25 to 2.50) |
| Attack number 3 | 0.50 (0.50 to 0.75) |
| Attack number 4 | 0.50 (0.25 to 1.00) |
| Attack number 5 | 0.75 (0.50 to 1.25) |
| Attack number 6 | 0.50 (0.25 to 1.25) |
| Attack number 7 | 0.75 (0.50 to 0.75) |
| Attack number 8 | 0.50 (0.25 to 0.75) |
| Attack number 9 | 0.25 (0.25 to 0.50) |
| Attack number 10 | 0.50 (0.25 to 0.75) |
Change in antigenic C1INH serum levels from pre-infusion to 1 hour after the initial dose of study drug.
| mg/dL | Open-label C1INH-nf |
|---|---|
| Pre-infusion | 10.7 ± 13.91 |
| Increase at 1 hour post-infusion | 9.6 ± 12.98 |
Percent change in functional C1INH serum levels from pre-infusion to 1 hour after the initial dose of study drug. Functional C1INH serum levels are expressed as a percent of total detectable C1INH (ie, functional C1INH/total detectable C1INH).
| percent of functional C1INH | Open-label C1INH-nf |
|---|---|
| Pre-infusion | 27.0 ± 19.30 |
| Percent increase at 1 hour post-infusion | 39.2 ± 18.04 |
Change in complement C4 serum levels from pre-infusion to 1 hour after the initial dose of study drug.
| mg/dL | Open-label C1INH-nf |
|---|---|
| Pre-infusion | 5.3 ± 5.41 |
| Change at 1 hour post-infusion | -0.2 ± 1.51 |
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.
| percent of attacks | Open-label C1INH-nf |
|---|---|
| Conservative Analysis | 87 |
| Less Conservative Analysis | 95 |
Non-serious events are listed at a 0.5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Open-label C1INH-nf | — | 0/113 (0%) | 1/113 (0.9%) |
| Event | Open-label C1INH-nf |
|---|---|
| Infusion site painGeneral disorders | 1/113 |
| RashSkin and subcutaneous tissue disorders | 1/113 |
| Age, Continuous(years) | Open-label C1INH-nf |
|---|---|
| Mean | 34.5 ± 17.6 |
| Sex: Female, Male(Participants) | Open-label C1INH-nf |
|---|---|
| Female | 75 |
| Male | 38 |
This study is completed, as verified in May 2021. You cannot join it, but the record below documents what was studied.
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