Expanded Access Program With Lanadelumab for Japanese People With Hereditary Angioedema

Open-arm, Japan Expanded Access Program With Lanadelumab (TAK-743) for Japanese Patients With Hereditary Angioedema

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.

This study is Japan Expanded Access Program with TAK-743. The study drug in this study is called TAK-743. TAK-743 will be administered to people who have Type I or II hereditary angioedema (HAE).

Two types of participants will be enrolled into this study:

• Participants who rollover from Study SHP643-302 (NCT04180163).
• Participants who are non-rollovers (ie, were not participants in Study SHP643-302).

Participants who discontinue from Study SHP643-302 after providing informed consent are not eligible to enroll in this study.

All participants will be asked to administer TAK-743 300 mg with subcutaneous injection every 2 weeks throughout this study. Participants who is stable with over 6-month administration of 300mg every 2 weeks can be switched to 300mg every 4 weeks.

This multi-center trial will be conducted in Japan (approximately 15 sites). The overall time to participate in this study is over 182 days. Participants will make multiple visits to the clinic basically every 2 weeks until Day 182, and will be contacted by telephone every 2 weeks after Day 182 plus multiple visit every 12 weeks after Day 182 for a follow-up assessment until study completion.

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.