Clinical trial NCT02865720: Study of C1 Inhibitor (Human) for the Prevention of Angioedema Attacks and Treatment of Breakthrough Attacks in Japanese Subjects With Hereditary Angioedema (HAE)
Official title: A Phase 3, Open-label, Single-period Study to Evaluate the Safety and Treatment Effect of Intravenous Administration of C1 Inhibitor (Human) for the Prevention of Angioedema Attacks and Treatment of Breakthrough Attacks in Japanese Subjects With Hereditary Angioedema (HAE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema (HAE)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-08-12
Enrollment: 8
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if an investigational treatment is safe and well tolerated when administered by intravenous (IV) infusion in Japanese subjects with HAE.


Eligibility criteria: Inclusion Criteria:

1. Be of Japanese descent, defined as born in Japan and having Japanese parents and Japanese maternal and paternal grandparents.
2. Be ≥2 years of age.
3. Meet the following minimum body weight criteria:

   * Subjects 2 to 5 years of age must weigh at least 12.5 kg; and
   * Subjects 6 years of age and above must weigh at least 25 kg.
4. Have a confirmed diagnosis of Type I or Type II HAE. NOTE: Diagnosis may be based on historical data including family history, clinical symptoms (characteristic attacks), or documentation of low level of C1 INH protein and/or C1 INH activity.
5. Have a history of at least one angioedema attack per month (on average) during the 3 consecutive months immediately before enrollment.
6. Agree to adhere to the protocol-defined schedule of assessments and procedures.
7. Agree to avoid his/her known angioedema attack triggers during the study to the best of his/her ability.
8. If a female of reproductive age, be postmenopausal (≥12 months following cessation of menstruation), surgically sterile, or following an acceptable method of birth control (and agree to continue its use through 1 month after the last dose of study drug):

   * Non-hormonal methods (eg, abstinence, barrier control) for at least 1 complete menstrual cycle before the Screening Visit.
   * Stable doses of estrogen and/or progestin containing products for at least 2 months before the Screening Visit.
9. If a male of reproductive age, be surgically sterile or agree to follow an acceptable method of birth control (eg, abstinence, barrier control) from the Screening Visit through 2 months after the last dose of study drug.
10. If an adult, be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed.

OR If a child or minor (\<20 years of age), have a parent/legal guardian who is informed of the nature of the study provide written informed consent (ie, permission) for the child to participate in the study before any study-specific procedures are performed. Assent will be obtained from children ≥14 years of age.

Exclusion Criteria:

1. Have a history of hypercoagulability (abnormal blood clotting).
2. Have a diagnosis of acquired angioedema or be known to have C1 INH antibodies.
3. Have a history of allergic reaction to C1 INH products, including CINRYZE (or any of the components of CINRYZE) or other blood products.
4. Have received C1 INH therapy or any blood products within 3 days before the first dose of study drug.
5. Have had signs or symptoms of an angioedema attack within 2 days before the first dose of study drug.
6. Have any change (start, stop, or change in dose) in androgen therapy (eg, danazol, oxandrolone, stanozolol, testosterone), tranexamic acid, epsilon-aminocaproic acid (EACA), or other antifibrinolytics within 14 days before the first dose of study drug.
7. If female, have started taking or changed the dose of any hormonal contraceptive regimen or hormone replacement therapy (eg, estrogen/progestin containing products) within 2 months before the first dose of study drug.
8. Be pregnant or breastfeeding.
9. Have received an investigational drug other than those required for prevention or treatment of angioedema attacks within 30 days before the first dose of study drug.
10. Have, as determined by the Investigator and/or the Sponsor's Medical Monitor, any surgical or medical condition that could interfere with the administration of study drug or interpretation of study results.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From start of study drug administration up to Week 12
measure: Number of Participants With Clinically Significant Abnormalities in Physical Examination Reported as Adverse Events (AEs)
timeFrame: From start of study drug administration up to Week 12
measure: Number of Participants With Potentially Clinically Important (PCI) Vital Signs Reported as Adverse Events (AEs)
timeFrame: Baseline up to Week 12
measure: Number of Participants With Potentially Clinically Important (PCI) Clinical Laboratory Assessments Reported as Adverse Events (AEs)
timeFrame: Baseline up to Week 12
measure: Concentration of C1 Esterase Inhibitor (C1 INH) Antigen (Protein Volume) at Week 1
timeFrame: Week 1: Pre-dose, 0.5, 1, 2, 6, 24, 48, 72 and 96 hours (h) post-dose
measure: Concentration of C1 Esterase Inhibitor (C1 INH) Antigen (Protein Volume) at Week 12
timeFrame: Week 12: Pre-dose, 0.5, 1, 2, 6, 24, 48, 72 and 96 h post-dose
measure: Concentration of Plasma Complement C4 at Week 1
timeFrame: Week 1: Pre-dose, 0.5, 1, 2, 6, 24, 48, 72 and 96 h post-dose
measure: Concentration of Plasma Complement C4 at Week 12
timeFrame: Week 12: Pre-dose, 0.5, 1, 2, 6, 24, 48, 72 and 96 h post-dose
measure: Concentration of Plasma Complement C1q at Week 1
timeFrame: Baseline (Week 1)
measure: Normalized Number of Angioedema Attacks (NNA) Per Month
timeFrame: Baseline up to Week 12
measure: Number of Participants With Angioedema Attacks in Different Anatomic Locations
timeFrame: Baseline up to Week 12
measure: Average Severity (Intensity) of Angioedema Attacks
timeFrame: Baseline up to Week 12
measure: Average Duration of Angioedema Attacks
timeFrame: Baseline up to Week 12
measure: Normalized Number of Angioedema Attacks (NNA) Per Month Treated With Rescue Medication
timeFrame: Baseline up to Week 12
measure: Number of Participants Achieving Clinical Responder Rate Relative to Historical Data
timeFrame: Baseline up to Week 12
measure: Change From Baseline in Angioedema Quality of Life (AE-QoL) in Treatment Period
timeFrame: Baseline, Week 12
measure: Number of Participants With Breakthrough Angioedema Attacks
timeFrame: Baseline up to Week 12
measure: Time From Attack Onset to Initial Improvement and Complete Resolution
timeFrame: Baseline up to Week 12
measure: Time From Onset of Attack to Time Treated by CINRYZE
timeFrame: Baseline up to Week 12
measure: Time From Treatment With CINRYZE to Initial Improvement
timeFrame: Baseline up to Week 12
Secondary outcomes:
Other outcomes:
Locations:
city: Toyohashi
country: Japan
facility: Toyohashi Municipal Hospital
state: Aiti
city: Maebashi
country: Japan
facility: Gunma University Hospital
state: Gunma
city: Kobe
country: Japan
facility: Kobe University Hospital
state: Hyogo
city: Nakagusuku
country: Japan
facility: Heart Life Hospital
state: Nakagami
city: Naha
country: Japan
facility: Naha City Hospital
state: Okinawa
city: Izumo
country: Japan
facility: Shiman University Hospital
state: Shimane
city: Asahi
country: Japan
facility: Asahi General Hospital
state: Tiba
city: Adachi
country: Japan
facility: Adachi kyosai Hospital
state: Tokyo
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Tomakomai
country: Japan
facility: Tomakomai City Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: