Safety, Tolerability, PK, PD of ADX-324 in Healthy Volunteers and Hereditary Angioedema Patients

The first-in-human Phase 1 study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of ADX-324 in healthy volunteers (HV) and in patients with Hereditary Angioedema (HAE).

Part A - HVInclusion Criteria:Male and female adults 18 to 55 years oldBody mass index (BMI) between 18 and 30 kg/m2Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studiesWilling and able to provide informed consent and comply with all study visitsExclusion Criteria:Any significant medical historyActive malignancy and/or history of malignancy in the past 5 yearsHistory of liver disease, Gilbert's syndrome, or abnormal liver function testEstimated creatinine clearance <60 mL/min or serum creatinine > 1.5-fold upper limit of normal.Any active infection or acute illnessMajor surgery or significant traumatic injury occurring within 3 monthsHave any other conditions that, in the opinion of the Investigator or Sponsor, would make the participant unsuitable for inclusion, or could interfere with the participant participating in or completing the study.Positive serology tests (HepB, Hep C, HIV)Use of any prescription, vaccines, supplements/vitamins, or over-the counter medicationTreatment with another investigational product within 30 days prior to the first study drug administrationKnown any clinically significant allergic reactions which, in the opinion of the Investigator, would interfere with the volunteer's ability to participate in the studyKnown hypersensitivity to any of the study drug ingredients.Pregnancy, intent to become pregnant during the course of the study, or lactating womenPart B - HAEInclusion Criteria:Male and female ≥18 years old, inclusive, at the time of signing the PICFConfirmed diagnosis of HAE Types I or IIEvidence of an average of (at least) one HAE attack per monthParticipants must have access to, and the ability to use, acute medication(s) to treat angioedema attacks.Body mass index (BMI) between 18 and 30 kg/m2Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studiesWilling and able to provide informed consent and comply with all study visitsExclusion Criteria:Concurrent diagnosis of any other type of chronic angioedemaHistory of clinically significant arterial or venous thrombosis, or current history of a clinically significant prothrombotic risk.Any significant medical historyActive malignancy and/or history of malignancy in the past 5 yearsAny active infection or acute illness, inclusive of cold/flu or COVID-19, within 30 days prior to the first study drug administration.Major surgery or significant traumatic injury occurring within 3 months prior to signature of the PICFHave any other conditions that, in the opinion of the Investigator or Sponsor, would make the participant unsuitable for inclusion, or could interfere with the participant participating in or completing the study.Positive serology tests for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).Use of C1-INH products, androgens, antifibrinolytics or other small molecule medications for routine prophylaxis within four half-lives prior to screeningMust have documented evidence of medical history of HAE attacksUse of any prescription, vaccines, supplements/vitamins, or over-the counter medication (with the exception of oral contraceptives) within 7 days prior to the first study drug administration.Treatment with another investigational product or biologic agent within 30 days prior to the study drug administrationHistory or presence of alcohol abuse or drug use within 30 days prior to the first study drug administration and throughout the study.Blood donation of 50 to 499 mL within 30 days prior to the first study drug administration or of >499 mL within 60 days prior to the first study drug administration.Pregnancy, intent to become pregnant during the course of the study, or lactating women.