Inclusion Criteria  Participants, or their legally appointed and authorized representatives, must provide written and signed informed consent form (ICF)/assent Participants must be aged ≥ 12 years at the time of informed consent and, as applicable, assent Participants must have a documented diagnosis of hereditary angioedema type 1 (HAE-1)/hereditary angioedema type 2 (HAE-2)  Participants must:  Experience a minimum of 2 HAE attacks (confirmed by the Investigator) during the Screening Period Be willing to complete the participant reported outcomes (PRO) assessments throughout the study Participants must have access to, and the ability to use acute medication(s) to treat angioedema attacks  Exclusion Criteria  Concurrent diagnosis of any other type of recurrent angioedema, including acquired, idiopathic angioedema or HAE with normal C1-INH (also known as HAE Type III) Any clinically-significant abnormalities in screening laboratory values that would render a participant unsuitable for inclusion in the study Treatment with another investigational drug or biological agent within 1 month or 5 half-lives, whichever is longer, of Screening Participated in a prior ISIS 721744 study  Exposure to any of the following medications:  Angiotensin-converting enzyme (ACE) inhibitors or any estrogen containing medications with systemic absorption within 4 weeks prior to Screening Chronic prophylaxis with Takhzyro, Haegarda, Cinryze or Orladeyo within 5 half-lives prior to Screening Oligonucleotides (including small interfering ribonucleic acid [siRNA]) within 4 months of Screening if single dose received, or within 12 months of Screening if multiple doses received. This exclusion does not apply to vaccines