Safety and Efficacy Study of CINRYZE for Prevention of Angioedema Attacks in Children Ages 6-11 With Hereditary Angioedema

Hereditary Angioedema (HAE) Clinical Trial

Official title:

A Phase 3, Multicenter, Randomized, Single-Blind, Dose-Ranging, Crossover Study to Evaluate the Safety and Efficacy of Intravenous Administration of CINRYZE® (C1 Esterase Inhibitor [Human]) for the Prevention of Angioedema Attacks in Children 6 to 11 Years of Age With Hereditary Angioedema

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02052141
• Other study ID #: 0624-301
• Secondary ID: 2013-002453-29SH
• Status: Completed
• Phase: Phase 3
• Start date: March 20, 2014
• Est. completion date: May 4, 2017

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective - To assess the relative efficacy of two dose levels of CINRYZE (500 Units and 1000 Units) administered by intravenous (IV) injection every 3 or 4 days to prevent angioedema attacks in children 6 to 11 years of age with hereditary angioedema (HAE).

Secondary Objectives - To assess the safety and tolerability, characterize the pharmacokinetics (PK) and pharmacodynamics (PD), and assess the immunogenicity of two dose levels of CINRYZE administered by IV injection in children 6 to 11 years of age with HAE.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 4, 2017
• Est. primary completion date: May 4, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 11 Years

Eligibility

Inclusion Criteria:

• Diagnosis of Type I or Type II HAE.

• History of angioedema attacks.

Exclusion Criteria:

• History of bleeding or clotting abnormality.

• Diagnosis of acquired angioedema or known to have C1 INH antibodies.

• History of allergic reaction to C1 esterase inhibitor or other blood products.

• Receipt of any experimental agents other than those required for prevention or treatment of angioedema attacks within 30 days prior to screening.

Related Conditions & MeSH terms

• Angioedema
• Hereditary Angioedema (HAE)

Intervention

Biological:
• CINRYZE 500
500 Units of CINRYZE administered by IV injection
• CINRYZE 1000
1000 Units of CINRYZE administered by IV injection

Locations

Country	Name	City	State
Germany	Klinikum der J.W. Goethe Universitat	Frankfurt
Germany	HZRM Hamophilie Zentrum Rhein Main GmbH	Mörfelden-Walldorf
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Mexico	Instituto Nacional de Pediatria	Mexico City
Romania	Clinical County Hospital Mures	Targu-Mures
United States	Asthma and Allergy Associates, P.C	Colorado Springs	Colorado
United States	Oregon Allergy Associates	Eugene	Oregon
United States	Nevada Access to Research and Education Society	Las Vegas	Nevada

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Countries where clinical trial is conducted

United States,  Germany,  Israel,  Mexico,  Romania, 

References & Publications (1)

Aygören-Pürsün E, Soteres D, Moldovan D, Christensen J, Van Leerberghe A, Hao J, Schranz J, Jacobson KW, Martinez-Saguer I. Preventing Hereditary Angioedema Attacks in Children Using Cinryze®: Interim Efficacy and Safety Phase 3 Findings. Int Arch Allergy — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Normalized Number of Angioedema Attacks Per Month in a Treatment Period	Angioedema attack was defined as the participant-reported indication of symptoms or signs such as swelling or pain at any location following a report of no swelling or pain on the previous day. Manifestations of an attack that progress from one site to another, prior to complete resolution, was considered a single attack. Attacks that began to regress and then worsened before complete resolution was also considered one attack. Attacks that began then appeared to resolve and then reappeared without a symptom-free calendar day reported after the appearance of resolution were considered 1 attack. Any events of swelling due to trauma or symmetrical nonpainful swelling of the lower extremities were not considered an angioedema attack. The number of attacks was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.	From start of treatment up to 12 weeks during each treatment period
Secondary	Cumulative Attack-severity Score of Angioedema Attacks Normalized Per Month in a Treatment Period	Severity of the angioedema attack sign/symptom was characterized as None: no symptom; Mild: noticeable symptom but easily tolerated by the participant and did not interfere with routine activities; Moderate: symptom interfered with the participant's ability to attend school or participate in family life and social/recreational activities; Severe: symptom significantly limited the participant's ability to attend school or participate in family life and social/recreational activities. Symptom severity score was assigned as Mild = 1, Moderate = 2 and Severe = 3. Cumulative attack severity score was the sum of the maximum symptom severity scores recorded for each angioedema attack in a treatment period. Cumulative attack-severity score normalized per month [(raw score/number of days of participation in that treatment period)*30.4] was reported here. Cumulative attack-severity score normalized per month ranged from 0 to 10.4 and higher scores represent worse symptoms.	From start of treatment up to 12 weeks during each treatment period
Secondary	Cumulative Daily-severity Score of Angioedema Attacks Normalized Per Month in a Treatment Period	Severity of the angioedema attack sign/symptom was characterized as None: no symptom; Mild: noticeable but easily tolerated by the participant and did not interfere with routine activities; Moderate: interfered with the participant's ability to attend school or participate in family life and social/recreational activities; Severe: significantly limited the participant's ability to attend school or participate in family life and social/recreational activities. Symptom severity score was assigned as Mild = 1, Moderate = 2 and Severe = 3. Cumulative daily-severity score was the sum of the severity scores recorded for every day of reported symptoms in a treatment period. Cumulative daily-severity score normalized per month [(raw score/number of days of participation in that treatment period)*30.4] was reported here. Cumulative daily-severity score normalized per month ranged from 0 to 15.6 and higher scores represent worse symptoms.	From start of treatment up to 12 weeks during each intervention period
Secondary	Normalized Number of Angioedema Attacks Per Month Requiring Acute Treatment in a Treatment Period	Angioedema attack was defined as the participant-reported indication of symptoms or signs such as swelling or pain at any location following a report of no swelling or pain on the previous day. Manifestations of an attack that progress from one site to another, prior to complete resolution, was considered a single attack. Attacks that began to regress and then worsened before complete resolution was also considered one attack. Attacks that began then appeared to resolve and then reappeared without a symptom-free calendar day reported after the appearance of resolution were considered 1 attack. Any events of swelling due to trauma or symmetrical nonpainful swelling of the lower extremities were not considered an angioedema attack. The number of attacks requiring acute treatment was normalized for the number of days participants participated in a given period and expressed as the monthly frequency.	From start of treatment up to 12 weeks during each intervention period
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) by Dose Group	An adverse event (AE) was any untoward, undesired, unplanned clinical event in the form of signs, symptoms, disease, or laboratory or physiological observations occurring in a participant participating in a clinical study with the sponsor's product, regardless of causal relationship. TEAEs were defined as events that started or worsened on or after the date and time of the first dose of investigational product and up to 7 days after the last dose of investigational product.	From start of study treatment up to 25 weeks
Secondary	Plasma Concentration of C1 Esterase Inhibitor (C1 INH) Antigen	C1 INH antigen concentration in plasma was determined using an automated nephelometric assay.	Pre-dose and 1 hour (h) post-dose at Week 1 (Dose 1) and Week 6 (Dose 12); Pre-dose, 1, 2, 4 and 8 h post-dose at Week 12 (Dose 24) of each intervention period
Secondary	C1 Esterase Inhibitor (C1 INH) Functional Activity in Plasma	The functional activity of C1 INH in plasma samples was determined by a chromogenic assay.	Pre-dose and 1 h post-dose at Week 1 (Dose 1) and Week 6 (Dose 12); Pre-dose, 1, 2, 4 and 8 h post-dose at Week 12 (Dose 24) of each intervention period
Secondary	Plasma Concentration of Complement C4	Concentration of Complement C4 in plasma was determined using an automated nephelometric assay.	Pre-dose and 1 h post-dose at Week 1 (Dose 1) and Week 6 (Dose 12); Pre-dose, 1, 2, 4 and 8 h post-dose at Week 12 (Dose 24) of each intervention period
Secondary	Number of Participants With C1 Esterase Inhibitor (C1 INH) Antibodies in Plasma	The presence of C1 INH antibodies in plasma samples was determined using a proprietary enzyme-linked-immunosorbent-assay. Number of participants with C1 INH Antibodies was reported.	Pre-dose, 1 week post treatment (Week 13, Week 25) and 1 month post treatment follow-up (Week 28)