Trial Outcomes & Findings for Open-Label C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks (NCT NCT00438815)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

113 participants

Primary outcome timeframe

Duration of the study (2.5 years)

Results posted on

2021-06-08

Participant Flow

Participant milestones

Participant milestones
Measure	Open-label C1INH-nf 1,000 Units (U) of C1 esterase inhibitor (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.
Overall Study STARTED	113
Overall Study COMPLETED	43
Overall Study NOT COMPLETED	70

Reasons for withdrawal

Reasons for withdrawal
Measure	Open-label C1INH-nf 1,000 Units (U) of C1 esterase inhibitor (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.
Overall Study Transferred to LEVP2006-4 (NCT00462709)	30
Overall Study 3-month follow-up no longer required	12
Overall Study Noncompliance with protocol requirements	9
Overall Study Transitioned to commercial C1INH-nf	6
Overall Study Lost to Follow-up	6
Overall Study Withdrawal by Subject	6
Overall Study Death	1

Baseline Characteristics

Open-Label C1 Esterase Inhibitor (C1INH-nf) for the Treatment of Acute Hereditary Angioedema (HAE) Attacks

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open-label C1INH-nf n=113 Participants 1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
Age, Continuous	34.5 years STANDARD_DEVIATION 17.6 • n=5 Participants
Sex: Female, Male Female	75 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants

PRIMARY outcome

Timeframe: Duration of the study (2.5 years)

Population: Intent-to-treat Efficacy (ITT-E) Population (N=101; the number of subjects who received at least one dose of C1INH-nf for the treatment of an acute HAE attack).

Outcome measures

Outcome measures
Measure	Open-label C1INH-nf n=101 Participants 1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
Number of Hereditary Angioedema (HAE) Attacks Treated With C1INH-nf Conservative Analysis	609 attacks
Number of Hereditary Angioedema (HAE) Attacks Treated With C1INH-nf Less Conservative Analysis	598 attacks

PRIMARY outcome

Timeframe: Within 4 hours after initial treatment

Population: ITT-E Population (N=101; the number of subjects who received at least one dose of C1INH-nf for the treatment of an acute HAE attack).

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.

Outcome measures

Outcome measures
Measure	Open-label C1INH-nf n=101 Participants 1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
Percent of HAE Attacks With Substantial Relief of the Defining Symptom Conservative Analysis	87 percent of attacks
Percent of HAE Attacks With Substantial Relief of the Defining Symptom Less Conservative Analysis	95 percent of attacks

SECONDARY outcome

Timeframe: Within 4 hours after initial treatment

Population: ITT-E Population.

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.

Outcome measures

Outcome measures
Measure	Open-label C1INH-nf n=101 Participants 1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
Time to Beginning of Substantial Relief of the Defining Symptom	0.75 hours Interval 0.5 to 1.0

SECONDARY outcome

Timeframe: Within 4 hours after initial treatment

Population: ITT-E subjects with at least 10 HAE attacks during the study (N=15).

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.

Outcome measures

Outcome measures
Measure	Open-label C1INH-nf n=15 Participants 1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments Attack number 1	1.50 hours Interval 0.75 to 4.0
Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments Attack number 2	0.50 hours Interval 0.25 to 2.5
Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments Attack number 3	0.50 hours Interval 0.5 to 0.75
Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments Attack number 4	0.50 hours Interval 0.25 to 1.0
Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments Attack number 5	0.75 hours Interval 0.5 to 1.25
Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments Attack number 6	0.50 hours Interval 0.25 to 1.25
Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments Attack number 7	0.75 hours Interval 0.5 to 0.75
Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments Attack number 8	0.50 hours Interval 0.25 to 0.75
Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments Attack number 9	0.25 hours Interval 0.25 to 0.5
Time to Beginning of Substantial Relief of the Defining Symptom for Subjects Who Received Multiple Treatments Attack number 10	0.50 hours Interval 0.25 to 0.75

SECONDARY outcome

Timeframe: Pre-infusion to 1 hour post-infusion

Population: ITT-E subjects with data at both sampling time points (N=84).

Change in antigenic C1INH serum levels from pre-infusion to 1 hour after the initial dose of study drug.

Outcome measures

Outcome measures
Measure	Open-label C1INH-nf n=84 Participants 1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
Antigenic C1 Inhibitor (C1INH) Serum Levels Pre-infusion	10.7 mg/dL Standard Deviation 13.91
Antigenic C1 Inhibitor (C1INH) Serum Levels Increase at 1 hour post-infusion	9.6 mg/dL Standard Deviation 12.98

SECONDARY outcome

Timeframe: Pre-infusion to 1 hour post-infusion

Population: ITT-E subjects with data at both sampling time points (N=82).

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).

Outcome measures

Outcome measures
Measure	Open-label C1INH-nf n=82 Participants 1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
Functional C1INH Serum Levels Pre-infusion	27.0 percent of functional C1INH Standard Deviation 19.30
Functional C1INH Serum Levels Percent increase at 1 hour post-infusion	39.2 percent of functional C1INH Standard Deviation 18.04

SECONDARY outcome

Timeframe: Pre-infusion to 1 hour post-infusion

Population: ITT-E subjects with data at both sampling time points (N=74).

Change in complement C4 serum levels from pre-infusion to 1 hour after the initial dose of study drug.

Outcome measures

Outcome measures
Measure	Open-label C1INH-nf n=74 Participants 1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
Complement C4 Serum Levels Pre-infusion	5.3 mg/dL Standard Deviation 5.41
Complement C4 Serum Levels Change at 1 hour post-infusion	-0.2 mg/dL Standard Deviation 1.51

Adverse Events

Open-label C1INH-nf

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Open-label C1INH-nf n=113 participants at risk 1,000 U of C1INH-nf administered IV. If there was no response to treatment 60 minutes after the first dose, a second 1,000 U dose could be administered.
General disorders Infusion site pain	0.88% 1/113 Presented are all treatment-emergent adverse reactions considered to be related to C1INH-nf.
Skin and subcutaneous tissue disorders Rash	0.88% 1/113 Presented are all treatment-emergent adverse reactions considered to be related to C1INH-nf.

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER