Efficacy and Safety of Lanadelumab (SHP643) in Japanese Participants With Hereditary Angioedema (HAE)
Condition: Hereditary Angioedema (HAE)
MeSH terms: Angioedema; Angioedemas, Hereditary
Intervention: Lanadelumab
Intervention description: Lanadelumab solution, SC
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

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.
    

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.