This study evaluates the safety and efficacy of long-term on-demand treatment with orally administered deucrictibant for acute hereditary angioedema (HAE) attacks, including laryngeal attacks. The study will enroll participants from Study PHA022121-C201 (NCT04618211), Study PHA022121-C306 (NCT06343779) and deucrictibant treatment naïve HAE-nC1INH adult participants who elect to participate in this extension study and meet the eligibility requirements.

Part A of the study will enroll adult participants from Study PHA022121-C201. The double-blind treatment assignment from Study PHA022121-C201 will be maintained.

Part B is open-label treatment and includes participants rolling over from Part A, participants from Study PHA022121-C201 who did not participate in Part A, participants aged 12 years and older with HAE type I, type II, or HAE-nC1INH rolling over from Study PHA022121-C306, and deucrictibant treatment naïve adult participants with HAE-nC1INH who elect to participate in this extension study and meet the eligibility requirements.

Key Inclusion Criteria:

1. Provision of the signed informed consent form by the participant and/ or legally designated representative. If the participant is a minor (i.e., <18 years of age or as determined by local law), consent will be obtained from the participant's parent/legally designated representative/guardian and signed assent will be obtained from the participant, per country regulations.

2. For participants from Study C201, received at least one dose of study drug (including the non-attack visit) in Study C201. For participants from Study C306, participant was randomized (and for adolescent participants ≥12 to <18 years received a dose of study drug in a non-attack state at Visit 1) and completed Study C306, with 2 attacks treated, or after closure of that study by the Sponsor. Enrollment of adolescents (≥12 to <18 years or age of adulthood as defined locally) from these studies is with consideration of local age requirements.

3. Female participants of childbearing potential (or who become of childbearing potential during the study) must agree to the protocol-specified pregnancy testing and to be abstinent from heterosexual intercourse or to use an acceptable contraception method as defined in the protocol and as available locally from enrollment until 30 days after the last study drug administration.

4. In the opinion of the Investigator, the participant (and parent/caregiver for adolescent participants) is willing and able to comply with the protocol.

5. Adult participants with HAE type III (HAE-nC1INH) who are deucrictibant-treatment naïve, must meet all of the following:

   i. Recurrent angioedema attacks with diagnostic testing results obtained during screening to confirm C1INH function ≥50% of normal and C4 level not below the lower level of the normal range performed by the central laboratory.

ii. Must either have:

1. Documented genetic mutation associated with HAE-nC1INH as listed in the Hereditary Angioedema Association (HAEA) and World Allergy Organization (WAO)/European Academy of Allergy and Clinical Immunology (EAACI) Guidelines.

   OR

2. If no documented mutation: clinical diagnosis with family history of HAE-nC1INH and documented elevations of bradykinin levels in blood. (US, UK and Canada only).

iii. Attacks not responding to treatments with high-dose antihistamine (cetirizine 40 mg/day or equivalent high-dose second-generation antihistamine medication) and no clinical attack symptoms relief if treated with corticosteroid, montelukast, or omalizumab.

iv. Documented effective attack symptom relief with on-demand icatibant treatment.

v. A history of at least 1 HAE attack in the last 3 months prior to Screening

Key Exclusion Criteria:

1. Any female who is pregnant, plans to become pregnant, or is breast-feeding.

2. Any other systemic disease (e.g., cardiovascular, gastrointestinal, renal, respiratory, neurological) or significant disease or disorder that, in the opinion of the Investigator, would interfere with the participant's safety or ability to participate in the study.

3. Use of lanadelumab for long-term HAE prophylactic therapy within 12 weeks prior to enrollment in Part A.

4. Participants who have recently used short or long-term HAE prophylaxis or on-demand HAE treatment will not be excluded from the study provided the following washout period is observed (i.e., study screening or enrollment/rollover should be delayed allowing for washout):

   i. For Part A:

   1. 2-week washout period before enrollment should be respected for participants who have used any C1-INH product, oral kallikrein inhibitors, attenuated androgens, or anti-fibrinolytics for long-term prophylactic HAE therapy.
   2. 1-week washout period before enrollment should be respected for participants who have used plasma derived C1-INH concentrates (Berinert, Cinryze, Haegarda) for on-demand treatment or short-term prophylaxis.
   3. 24-hour washout period before enrollment should be respected for participants who have used recombinant C1-INH (Ruconest) for on-demand treatment or short-term prophylaxis.

   ii. For Part B:

   a. If a participant is receiving long-term prophylactic therapy with a medication indicated for HAE:, eg, plasma-derived C1INH, danazol at less than or equal to 200 mg/day, antifibrinolytics, berotralstat, or lanadelumab, they must be on a stable dose and regimen for at least 3 months before screening and intends to remain on the same dose for the duration of the study.

5. History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse

6. Participation in any other investigational drug study within (except with deucrictibant) currently, within the last 30 days prior to the first deucrictibant dose or within 5 half-lives of study drug at enrollment, whichever is longer.

7. Discontinued from parent study after enrollment for any study drug-related safety reason or non-compliance including significant protocol deviation.

8. Use of concomitant medications that are strong CYP3A4 inhibitors (e.g., clarithromycin, erythromycin, itraconazole, ketoconazole, ritonavir) or strong CYP3A4 inducers (e.g., carbamazepine and phenytoin).