Trial Outcomes & Findings for Open-Label C1 Esterase Inhibitor (C1INH-nf) for the Prevention of Acute Hereditary Angioedema (HAE) Attacks (NCT NCT00462709)

Results Overview

A hereditary angioedema (HAE) attack was defined as a discrete episode during which the subject progressed from no angioedema to symptoms of angioedema.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

146 participants

Primary outcome timeframe

Duration of the study

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) every 3 to 7 days.
Overall Study STARTED	146
Overall Study COMPLETED	79
Overall Study NOT COMPLETED	67

Reasons for withdrawal

Reasons for withdrawal
Measure	Open-label C1INH-nf 1,000 Units (U) of C1 esterase inhibitor (C1INH-nf) administered intravenously (IV) every 3 to 7 days.
Overall Study Transitioned to commercial C1INH-nf	40
Overall Study Lost to Follow-up	10
Overall Study Withdrawal by Subject	8
Overall Study Transferred to LEVP2006-1 (NCT00438815)	3
Overall Study Death	2
Overall Study Logistical reasons	2
Overall Study Physician Decision	1
Overall Study Withdrew to start treatment with Cetor	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open-label C1INH-nf n=146 Participants 1,000 U of C1INH-nf administered IV every 3 to 7 days.
Age, Continuous	36.5 years STANDARD_DEVIATION 16.48 • n=5 Participants
Sex: Female, Male Female	112 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants

PRIMARY outcome

Timeframe: Duration of the study

Population: Intent-to-treat Efficacy (ITT-E) Population (N=146; the number of subjects who received at least one prophylactic dose of C1INH-nf for the prevention of HAE attacks). HAE attack frequency was reported by 137 subjects at screening (i.e., data were missing for 9 subjects).

A hereditary angioedema (HAE) attack was defined as a discrete episode during which the subject progressed from no angioedema to symptoms of angioedema.

Outcome measures

Outcome measures
Measure	Open-label C1INH-nf n=146 Participants 1,000 U of C1INH-nf administered IV every 3 to 7 days.
Frequency of All HAE Attacks At Screening (N=137)	3.00 attacks per month Interval 0.08 to 28.0
Frequency of All HAE Attacks During Prophylactic Therapy with C1INH-nf (N=146)	0.21 attacks per month Interval 0.0 to 4.56

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-infusion to 1 hour post-infusion

Population: ITT-E subjects with data at both sampling time points (N=137).

Change from pre-infusion to 1 hour post-infusion in antigenic C1INH serum levels.

Outcome measures

Outcome measures
Measure	Open-label C1INH-nf n=137 Participants 1,000 U of C1INH-nf administered IV every 3 to 7 days.
Antigenic C1 Inhibitor (C1INH) Serum Levels Pre-infusion	17.1 mg/dL Standard Deviation 19.67
Antigenic C1 Inhibitor (C1INH) Serum Levels Increase at 1 hour post-infusion	8.6 mg/dL Standard Deviation 11.89

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-infusion to 1 hour post-infusion

Population: ITT-E subjects with data at both sampling time points (N=132).

Change from pre-infusion to 1 hour post-infusion in functional C1INH serum levels. Functional C1INH serum levels are expressed as a percent of total detectable C1INH (i.e., functional C1INH/total detectable C1INH).

Outcome measures

Outcome measures
Measure	Open-label C1INH-nf n=132 Participants 1,000 U of C1INH-nf administered IV every 3 to 7 days.
Functional C1INH Serum Levels Pre-infusion	42.0 percent Standard Deviation 25.85
Functional C1INH Serum Levels Percent increase at 1 hour post-infusion	30.4 percent Standard Deviation 18.05

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-infusion to 1 hour post-infusion

Population: ITT-E subjects with data at both sampling time points (N=134).

Change from pre-infusion to 1 hour post-infusion in complement C4 serum levels.

Outcome measures

Outcome measures
Measure	Open-label C1INH-nf n=134 Participants 1,000 U of C1INH-nf administered IV every 3 to 7 days.
Complement C4 Serum Levels Pre-infusion	10.1 mg/dL Standard Deviation 8.17
Complement C4 Serum Levels Change at 1 hour post-infusion	-0.1 mg/dL Standard Deviation 3.61

Adverse Events

Open-label C1INH-nf

Serious events: 0 serious events

Other events: 9 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=146 participants at risk 1,000 U of C1INH-nf administered IV every 3 to 7 days.
Gastrointestinal disorders Nausea	1.4% 2/146 Presented are treatment-emergent adverse reactions considered to be related to C1INH-nf. There were no serious adverse reactions considered related to C1INH-nf.
Nervous system disorders Headache	2.1% 3/146 Presented are treatment-emergent adverse reactions considered to be related to C1INH-nf. There were no serious adverse reactions considered related to C1INH-nf.
Skin and subcutaneous tissue disorders Rash	2.1% 3/146 Presented are treatment-emergent adverse reactions considered to be related to C1INH-nf. There were no serious adverse reactions considered related to C1INH-nf.
Vascular disorders Phlebitis	1.4% 2/146 Presented are treatment-emergent adverse reactions considered to be related to C1INH-nf. There were no serious adverse reactions considered 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