Long-term Safety and Efficacy Study of DX-2930 (SHP643) to Prevent Acute Angioedema Attacks in Patients With Type I and Type II HAE
Condition: Hereditary Angioedema (HAE)
MeSH terms: Angioedema; Angioedemas, Hereditary
Intervention: DX-2930; DX-2930
Intervention description: Participants who rollover from the DX-2930-03 study will receive 300 milligram (mg) DX-2930 subcutaneous injection at Day 0 followed by second dose following the first HAE attack and then once in every 2 weeks until the end of the treatment period (up to 924 days). A wash-out period of a minimum of 10 days and a maximum of 18 days is required between subsequent administrations.; Participants who were not participants in DX-2930-03 will receive 300 milligram (mg) DX-2930 subcutaneous injection once in every 2 weeks until the end of the treatment period (up to 924 days).
Intervention MeSH terms: Antibodies, Monoclonal
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 212.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: DX-2930(SHP643); Dyax; Hereditary Angioedema

Summary:

      This study is an open-label, long term safety and efficacy study to evaluate DX-2930 in
      preventing acute angioedema attacks in participants with Type I and Type II HAE.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female HAE participants who are 12 years of age or older at the time of
             screening

          -  Documented diagnosis of HAE (Type I or II) based on

               1. Documented clinical history consistent with HAE (subcutaneous or mucosal,
                  nonpruritic swelling episodes without accompanying urticaria).

               2. Diagnostic testing results obtained during screening (or a prior DX-2930 study)
                  that confirm HAE Type I or II: C1 inhibitor (C1-INH) functional level less than
                  (<) 40 percentage (%) 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. Participants may be retested if results are incongruent
                  with clinical history or believed by the investigator to be confounded by
                  long-term prophylactic (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 Medical Monitor is advised for proper documentation of
                  eligibility).

               3. At least one of the following: Age at reported onset of first angioedema symptoms
                  less than or equal to (<=) 30 years, a family history consistent with HAE Type I
                  or II, or C1q within normal range.

          -  A historical baseline HAE attack rate of at least 1 attack per 12 weeks

          -  Adult participants and caregivers of participants under the age of 18 are willing and
             able to read, understand, and sign an informed consent form. Participants age 12 to
             17, whose caregiver has provided informed consent, are willing and able to read,
             understand and sign an assent form.

          -  Males and females who are fertile and sexually active must adhere to contraception
             requirements for the duration of the study as

               1. Females (NOTE: Female rollover participants (those who previously participated in
                  Study DX-2930-03 [NCT02586805]) of childbearing potential may continue to use the
                  birth control method used during Study DX-2930-03 (NCT02586805).) of childbearing
                  potential must agree to be abstinent or it is recommended to use highly effective
                  forms of contraception from the screening period through 30 days after the final
                  study visit. This includes stable doses (for 3 months prior to study screening)
                  of combined estrogen and progestin-containing hormonal contraception associated
                  with inhibition of ovulation (oral, injectable or implantable), progestin-only
                  hormonal contraception associated with inhibition of ovulation, intra-uterine
                  device (IUD, all types) or intrauterine hormone releasing systems (IUS). Notes:
                  1) A female whose male partner has had a vasectomy must agree to use one
                  additional form of medically acceptable contraception. 2) Use of a male condom
                  with or without spermicide or cervical cap, diaphragm or sponge with spermicide
                  or a combination (double barrier methods) are not considered highly effective.

               2. Females of non-childbearing potential, defined as surgically sterile (status post
                  hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or
                  post-menopausal for at least 12 months do not require contraception during the
                  study.

               3. 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 60
                  days after the final study visit.

        Exclusion Criteria:

          -  Discontinued from DX-2930-03 (NCT02586805) after enrollment for any reason.

          -  If rolling over from DX-2930-03 (NCT02586805), presence of important safety concerns
             that would preclude participation in this study.

          -  Concomitant diagnosis of another form of chronic, recurrent angioedema, such as
             acquired angioedema (AAE), HAE with normal C1 inhibitor (also known as HAE Type III),
             idiopathic angioedema, or recurrent angioedema associated with urticaria.

          -  Dosing with an investigational drug (not including DX-2930 or other HAE therapies) or
             exposure to an investigational device within 4 weeks prior to screening.

          -  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.

          -  Unwilling to discontinue use of long-term prophylactic therapy for HAE (C1-INH,
             attenuated androgens, or anti-fibrinolytics) within 3 weeks after starting DX-2930
             treatment.

          -  Any of the following liver function test abnormalities: alanine aminotransferase (ALT)
             > 3x upper limit of normal, or aspartate aminotransferase (AST) > 3x upper limit of
             normal, or total bilirubin > 2x upper limit of normal (unless the bilirubin elevation
             is a result of Gilbert's Syndrome).

          -  Pregnancy or breastfeeding.

          -  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, a significant pre-existing illness or other major comorbidity that the
             investigator considers may confound the interpretation of study results).