This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, 2-period, 2-treatment cross-over study to evaluate the efficacy and safety of orally administered deucrictibant compared to placebo for the on-demand treatment of HAE attacks, including non-severe laryngeal attacks, in participants ≥12 to ≤75 years of age with HAE type 1, type 2, or type 3, a proportion of whom are using long-term prophylactic medication for HAE.

The study consists of a Screening Phase during which eligibility is confirmed, a Treatment Phase in which participants will be randomized and receive double blinded study drug to treat 2 qualifying HAE attacks (i.e., 2 Treatment Periods within the Treatment Phase), and an End-of-Study Follow-up Phase after the second attack treated with study drug. In addition, for adolescent participants (age ≥12 to <18 years), PK samples are collected after administration of deucrictibant at Day 1 in a non-attack state.

Inclusion Criteria:

1. Provision of written informed consent/assent.
2. Male or female, aged ≥12 to ≤75 years at the time of providing written informed consent/assent.
3. Diagnosis of HAE-1/2/3.
4. History of at least 2 HAE attacks in the last 3 months before screening.
5. Experience with using standard-of-care treatment to effectively manage on-demand treatment for HAE attacks.
6. Participants on long-term prophylactic therapy with plasma-derived C1-INH (danazol, anti-fibrinolytics, berotralstat, or lanadelumab) must be on a stable dose and regimen and intend to remain on the same dose for 6 months before screening and the duration of the study. OR, Participant has stopped using plasma-derived C1-INH (danazol, anti-fibrinolytics, berotralstat) at least 2 weeks or lanadelumab at least 10 weeks before screening.
7. Capable of recording, without assistance, electronic HAE diary and ePRO data using an electronic device.
8. For adolescent participants aged ≥12 and <18 years of age: body weight ≥40 kg.
9. Female participants of childbearing potential must agree to the protocol specified pregnancy testing and contraception methods.

Exclusion Criteria:

1. Any female who is pregnant, plans to become pregnant, or is breastfeeding.
2. Any diagnosis of angioedema other than HAE.
3. Any clinically significant comorbidity or systemic dysfunction that would interfere with the participant's safety or ability to participate in the study.
4. Use of attenuated androgens for short-term prophylaxis within 2 weeks before screening.
5. Abnormal hepatic function.
6. Abnormal renal function (eGFR <60 ml/min/1.73 m2).
7. History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse.
8. Has received prior on-demand HAE treatment with deucrictibant.
9. Currently participating in any other investigational drug study or receiving other investigational treatment within the last 30 days, or within 5 half-lives (whichever is longer) of the time of randomization.
10. Prior gene therapy for any indication at any time.
11. Use of concomitant medications with systemic absorption that are strong inhibitors of CYP3A4 or strong inducers of CYP3A4 within the last 30 days, or within 5 half-lives (whichever is longer) of the time of randomization.
12. Known hypersensitivity to study drug or any of the excipients of study drug.