Clinical trial NCT04180163: Efficacy and Safety of Lanadelumab (SHP643) in Japanese Participants With Hereditary Angioedema (HAE)
Official title: A Phase 3 Multi-center, Open-label Study to Evaluate the Efficacy and Safety of Lanadelumab (SHP643) in Japanese Subjects With Hereditary Angioedema
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hereditary Angioedema (HAE)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2019-11-27
Enrollment: 12
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this phase 3, open-label, multi-center study is to evaluate the safety and efficacy of lanadelumab in Japanese participants with HAE Type I or II.

Detailed description: This study will consist of 52-week treatment period and a 4-week follow-up period. 52-week treatment period comprises of a 26-week treatment period A (Day 0 to Day 182) and a 26-week treatment period B (Day 183 to Day 364). Participants who complete treatment period A will immediately continue into treatment period B. After completion of treatment period B participants may roll over into an expanded access study TAK-743-5007 (NCT04687137). Participants who elect to rollover to Study TAK-743-5007 will complete their end of study (EOS) assessments on Day 378. All other participants will complete their EOS assessments on Day 392.

Eligibility criteria: Inclusion Criteria:

* Be of Japanese descent, defined as born in Japan and having Japanese parents and Japanese maternal and paternal grandparents.
* The participant is male or female and \>= 12 years of age at the time of informed consent.
* Documented diagnosis of HAE (Type I or II) based upon all of the following:

  1. Documented clinical history consistent with HAE (subcutaneous or mucosal, nonpruritic swelling episodes without accompanying urticaria).
  2. Diagnostic testing results obtained during screening that confirm HAE Type I or II: C1 inhibitor (C1-INH) functional level \<40% of the normal level. Participants with functional C1-INH level 40-50% of the normal level may be enrolled if they also have a C4 level below the normal range. With prior sponsor approval, participants may be retested during the run-in period if results are in congruent with clinical history or believed by the investigator to be confounded by recent C1 inhibitor use.
  3. At least one of the following: age at reported onset of first angioedema symptoms \<=30 years, a family history consistent with HAE Type I or II, or C1q within normal range.
* Attack rate: Participants must experience at least 1 investigator-confirmed HAE attack per 4 weeks during the run-in period to enter the lanadelumab treatment period.
* The participant (or the participants parent/legal authorized representative, if applicable) has provided written informed consent approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC).
* If the participant is an adult, be informed of the nature of the study and provide written informed consent before any study-specific procedures are performed or if the participant is a minor (ie, below the age of majority), have a parent/legally authorized representative who is informed of the nature of the study provide written informed consent (ie, permission) for the minor to participate in the study before any study-specific procedures are performed. Assent will be obtained from minor participants.
* Males, or non pregnant, non lactating females who are fertile and sexually active and who agree to be abstinent or agree to comply with the applicable contraceptive requirements of this protocol for the duration of the study, or females of non child bearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or postmenopausal for at least 12 months.
* Agree to adhere to the protocol-defined schedule of assessments and procedures.

Exclusion Criteria:

* Concomitant diagnosis of another form of chronic, recurrent angioedema, such as acquired angioedema (AAE), HAE with normal C1-INH (also known as HAE Type 3), idiopathic angioedema, or recurrent angioedema associated with urticaria.
* Participation in a prior lanadelumab study.
* Dosing with investigational drug or exposure to an investigational device within 4 weeks prior to entering to screening.
* Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systematic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks prior to screening.
* Exposure to androgens (eg, danazol, methyltestosterone, testosterone) within 2 weeks prior to entering the run-in period.
* Use of long-term prophylactic therapy for HAE (C1-INH, attenuated androgens, or anti-fibrinolytics) within 2 weeks prior to entering the run in period.
* Use of short-term prophylaxis for HAE 7 days prior to entering the run-in period. Short-term prophylaxis is defined as C1-INH, attenuated androgens, or anti-fibrinolytics used to avoid angioedema complications from medically indicated procedures.
* Any of the following liver function abnormalities: alanine aminotransferase (ALT) \>3x upper limit of normal, or aspartate aminotransferase (AST) \>3x upper limit of normal or bilirubin \>2x upper limit of normal (unless the bilirubin is a result of Gilbert's syndrome).
* Pregnancy or breast feeding.
* Participant has any condition that in the opinion of the investigator or sponsor, may compromise their safety or compliance, preclude successful conduct of the study, or interfere with interpretation of the results (eg, history of substance abuse, or dependence, significant preexisting illnesses or major comorbidity the investigator considers may confound the interpretation of the study results).
* Participant has a known hypersensitivity to the IP or its components.

Primary outcomes:
measure: Number of Participants Achieving Attack-Free Status for the Efficacy Evaluation Period of Day 0 Through Day 182
timeFrame: Day 0 through Day 182
Secondary outcomes:
measure: Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods
timeFrame: Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364
measure: Number of Investigator-Confirmed Hereditary Angioedema (HAE) Attacks Requiring Acute Treatment During Each of the Efficacy Evaluation Periods
timeFrame: Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364
measure: Number of Moderate or Severe Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods
timeFrame: Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364
measure: Number of Participants With Maximum Hereditary Angioedema (HAE) Attack Severity During Each of the Efficacy Evaluation Periods
timeFrame: Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364
measure: Number of High-Morbidity Investigator-Confirmed Hereditary Angioedema (HAE) Attacks During Each of the Efficacy Evaluation Periods
timeFrame: Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364
measure: Time to First Hereditary Angioedema (HAE) Attack After Day 0 for the Efficacy Evaluation Period
timeFrame: Day 0 through Day 182
measure: Time to First Hereditary Angioedema (HAE) Attack After Day 0 for the Efficacy Evaluation Period
timeFrame: Day 70 through Day 182
measure: Number of Participants Achieving at Least 50%, 70% and 90% Reduction in the Investigator-Confirmed Normalized Number of Attacks (NNA) Per 4 Weeks Relative to the Run-in Period NNA for Each of Efficacy Evaluation Periods
timeFrame: Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364
measure: Number of Participants Achieving Normalized Number of Attacks (NNA) <1.0 Per 4 Weeks, <0.75 Per 4 Weeks, <0.50 Per 4 Weeks and <0.25 Per 4 Weeks for Each of the Efficacy Evaluation Periods
timeFrame: Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364
measure: Number of Participants Achieving Attack-Free Status for the Efficacy Evaluation Period Day 0 Through Day 364, Day 70 Through Day 182, and Day 70 Through Day 364
timeFrame: Day 0 through Day 364, Day 70 through Day 182, and Day 70 through Day 364
measure: Number of Participants Achieving Attack-Free Status for Monthly Increments
timeFrame: At Months 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 13
measure: Number of Participants Achieving Investigator-Confirmed Hereditary Angioedema (HAE) Attack-Free Intervals
timeFrame: Day 0 through Day 182
measure: Percentage of Attack Free Days During Each of the Efficacy Evaluation Periods
timeFrame: Day 0 through Day 182, Day 0 through Day 364, Day 70 through Day 182, Day 70 through Day 364
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Including Adverse Events of Special Interest (AESI) and Serious Adverse Events (SAEs)
timeFrame: From first dose of the study drug up to end of study (EOS) (up to Day 392)
measure: Plasma Concentrations of Lanadelumab
timeFrame: Predose on Days 0, 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392
measure: Change From Baseline in Angioedema Quality of Life (AE-QoL) Questionnaire Total Score
timeFrame: Days 0, 28, 56, 98, 126, 154, 182, 266, 364, 378 or 392
measure: Plasma Kallikrein (pKal) Activity
timeFrame: Predose on Days 0, 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392
measure: Number of Participants With Positive Anti-drug Antibody (ADA) in Plasma
timeFrame: Predose on Days 0 (or Baseline), 56, 98, 140, 182, 266, 350, 364, and at any time on Day 378 or 392
measure: Number of Participants With TEAEs Related to Clinical Laboratory Tests
timeFrame: From first dose of the study drug up to end of study (EOS) (up to Day 392)
measure: Number of Participants With TEAEs Related to Vital Signs
timeFrame: From first dose of the study drug up to end of study (EOS) (up to Day 392)
measure: Number of Participants With TEAEs Related to Electrocardiogram (ECG)
timeFrame: From first dose of the study drug up to end of study (EOS) (up to Day 392)
Other outcomes:
Locations:
city: Toyohashi-shi
country: Japan
facility: Toyohashi Municipal Hospital
state: Aichi-Ken
city: Asahi-shi
country: Japan
facility: Asahi General Hospital
state: Chiba-Ken
city: Ogaki-shi
country: Japan
facility: Ogaki Municipal Hospital
state: Gifu-Ken
city: Hiroshima-shi
country: Japan
facility: Hiroshima University Hospital
state: Hiroshima-Ken
city: Tomakomai-shi
country: Japan
facility: Tomakomai City Hospital
state: Hokkaido
city: Kobe-shi
country: Japan
facility: Kobe University Hospital
state: Hyogo-Ken
city: Isehara-shi
country: Japan
facility: Tokai University Hospital
state: Kanagawa-Ken
city: Yokohama-shi
country: Japan
facility: Yokohama City University Hospital
state: Kanagawa-Ken
city: Kyoto-shi
country: Japan
facility: Kyoto University Hospital
state: Kyoto-Fu
city: Suita-shi
country: Japan
facility: Osaka University Hospital
state: Osaka-Fu
city: Soka-shi
country: Japan
facility: Saiyu Soka Hospital
state: Saitama-Ken
city: Izumo-shi
country: Japan
facility: Shimane University Hospital
state: Shimane-Ken
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: