Expanded Access Program With Lanadelumab for Japanese People With Hereditary Angioedema
Condition: Hereditary Angioedema
MeSH terms: Angioedema; Angioedemas, Hereditary
Intervention: TAK-743 300 mg
Intervention description: TAK-743 300 mg, subcutaneous injection every 2 or 4 weeks
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 expanded access program allows people to gain access to an unlicensed treatment on
      compassionate grounds. Lanadelumab, also known as TAK-743, is a medicine to help prevent
      hereditary angioedema attacks. Lanadelumab is not yet licensed for use in Japan.

      The main aim of this study is to allow Japanese teenagers and adults with type I or type II
      hereditary angioedema to be treated with lanadelumab, through the expanded access program in
      Japan.

      Participants can either have taken part in the previous study SHP643-302 or can be new
      participants. Participants just completing study SHP643-302 who reach the criteria can
      automatically take part in this study. However, for new participants, the study doctor will
      check who can take part at the first study visit.

      For those who can take part, new participants will receive injections of lanadelumab just
      under the skin. Eventually, after training, some of these will be able to inject themselves
      with lanadelumab in the same way. Participants who injected themselves with lanadelumab in
      study SHP643-302 can continue to do so during this study.

      The study doctors will decide if each participant will be treated with lanadelumab every 2
      weeks or every 4 weeks. Treatment with lanadelumab will continue until lanadelumab is
      commercially available in Japan or the sponsor (Takeda) stops the study.

      Participants can visit the clinic during treatment if needed. If treatment continues after 6
      months, participants will visit the clinic every 12 weeks for a check-up. This will include
      noting any hereditary angioedema attacks and side effects from the treatment. After 7 months
      of treatment, the study staff will check-up with each participant every 2 weeks by telephone.

      After treatment has finished, participants will visit the clinic for a final-check-up 4 weeks
      later.
    

Eligibility criteria:

        Inclusion Criteria:

          1. In the opinion of the Investigator, the participant is capable of understanding and
             complying with protocol requirements.

          2. Be of Japanese descent, defined as born in Japan and having Japanese parents and
             Japanese maternal and paternal grandparents.

          3. Male and female HAE participants who are 12 years of age or older at the time of
             screening.

          4. Documented diagnosis of disease HAE (Type I or II) based on all of the following:

               -  Documented clinical history consistent with HAE (subcutaneous [SC] or mucosal,
                  nonpruritic swelling episodes without accompanying urticaria).

               -  Diagnostic testing results obtained during screening (or a prior lanadelumab
                  study) 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% to 50% of the
                  normal level may be enrolled if they also have a C4 level below the normal range.
                  Participants may be retested if results are incongruent with clinical history or
                  believed by the Investigator to be confounded by long-term prophylaxis (LTP) use.
                  It is understood that C1-INH therapy may alter the lab results of C1-INH
                  assessments; therefore, the Investigator's discretion in collaboration with
                  sponsor is advised for proper documentation of eligibility.

               -  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.

          5. Non-rollover participants only: A historical baseline HAE attack rate of at least 1
             attack per 4 weeks in the recent 1 year.

          6. Rollover participants only: Participants from Study SHP643-302 are permitted to
             rollover and enroll into this study if:

               -  They completed the treatment period of Study SHP643-302; and

               -  They consented to enter Study TAK-743-5007 on or before Day 350 of the SHP643-302
                  study (since Day 378 of Study SHP643-302 is also Day 0 of Study TAK-743-5007,
                  informed consent may be completed on Day 364 or this visit, if not already
                  provided).

          7. Adult participants and caregivers of subjects under the age of 20 are willing and able
             to read, understand, and sign an informed consent form. Participants aged 12 to 19,
             whose caregiver has provided informed consent, are willing and able to read,
             understand and sign an informed consent form (an assent form, if applicable) as much
             as possible.

          8. Agree to adhere to the protocol-defined schedule of treatments, assessments, and
             procedures.

          9. Males and females who are fertile and sexually active must adhere to contraception
             requirements for the duration of the study as follows:

               -  Females of childbearing potential must agree to be abstinent or it is recommended
                  to use highly effective forms of contraception from the screening period through
                  70 days after the final study visit.

               -  Females of nonchildbearing potential, defined as surgically sterile (status
                  post-hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or
                  postmenopausal for at least 12 months do not require contraception during the
                  study.

               -  Males, including males who are surgically sterile (post-vasectomy), with female
                  partners of childbearing potential must agree to be abstinent or else use a
                  medically acceptable form of contraception from the screening period through 70
                  days after the final study visit.

        Exclusion Criteria:

          1. If rolling over from Study SHP643-302, presence of important safety concerns that
             would preclude participation in this study.

          2. Concomitant diagnosis of another form of chronic, recurrent angioedema such as
             acquired angioedema, HAE with normal C1-INH (also known as HAE Type III/normal
             C1-INH), idiopathic angioedema, or recurrent angioedema associated with urticaria.

          3. Dosing with an investigational drug (not including lanadelumab or other HAE therapies)
             or exposure to an investigational device within 4 weeks prior to screening.

          4. Exposure to angiotensin-converting enzyme (ACE) inhibitors within 4 weeks prior to
             screening or any newly initiated or dose modification of estrogen-containing
             medications with systemic absorption (such as oral contraceptives or hormonal
             replacement therapy) 3 months prior to the screening visit.

          5. Unwilling to discontinue short or long-term prophylactic therapy for HAE, eg, C1-INH,
             attenuated androgens or anti-fibrinolytics within 3 weeks after starting the treatment
             period. Short-term prophylaxis is defined as C1-INH, attenuated androgens, or
             antifibrinolytic used to avoid angioedema complications from medically indicated
             procedures.

          6. Any of the following liver function test abnormalities: alanine aminotransferase (ALT)
             >3 × upper limit of normal (ULN), or aspartate aminotransferase (AST) >3 × ULN, or
             total bilirubin >2 × ULN (unless the bilirubin elevation is a result of Gilbert's
             syndrome).

          7. Pregnancy or breast feeding.

          8. Have any uncontrolled underlying medical condition which would require treatment
             adjustment during the study treatment period, that, in the opinion of the Investigator
             or sponsor, may confound the results of the safety assessments or may place the
             participant at risk. Participants with stable treatment for at least 3 months prior to
             screening and NOT expecting any change to their treatment regimen for 6 months during
             the study treatment period, will not be excluded.

          9. Participant has a known hypersensitivity to the study drug or its components.