Oral ONCE Daily prophylaxis with PHA-022121 in Patients with Acquired C1-Inhibitor Deficiency

- Provision of signed and dated informed consent form - Male or female, aged >=
35 at enrolment - Diagnosis of AAE-C1-INH based upon all of the following: 1.
Documented clinical history consistent with AAE-C1-INH (subcutaneous or
mucosal, nonpruritic swellings without accompanying urticaria and C1-INH
activity < 0.63mE/L) 2. At least one of the following: • Age at reported onset
of first angioedema symptoms >= 40 years AND family history negative for
angioedema • C1q below lower limit of normal (88 kU/L) AND absence of SERPING1
mutation • Serological confirmation of antibodies against C1-INH - Documented
history of at least three angioedema attacks in the last four months, or at
least two angioedema attacks in the last two months. For patients that
previously participated in POP-AID part 2, a historical attack-rate of at least
three attacks in four months or two attacks in two months previous to the start
of POP-AID part 2 is required • Reliable access to and experience with using
icatibant to effectively manage acute angioedema attacks • Female patients of
childbearing potential must agree to be abstinent or to use highly effective
forms of contraception methods from enrolment through the end of the study.
This includes progestin-only oral contraceptive associated with inhibition of
ovulation (oral, injectable, or implantable), intrauterine device (IUD, all
types) or intrauterine hormone releasing systems (IUS). A female of
childbearing potential whose male partner has had a vasectomy must agree to use
one additional form of medically acceptable contraception. • Male patients,
including males who are surgically sterile (post vasectomy), who have a female
partner of childbearing potential must agree to be sexually abstinent or use a
medically acceptable form of barrier contraception for two weeks after each
administration of study drug. In addition, they must agree to not donate sperm
during study participation.

• Pregnancy or breast-feeding • Clinically significant abnormal ECG, most
notably a QTcF > 470 ms (for females) or > 450 ms (for males) • Any clinically
significant history of angina, myocardial infarction, syncope, stroke, left
ventricular hypertrophy or cardiomyopathy, or any other cardiovascular
abnormality within the previous year • Any other systemic disease (e.g.,
gastrointestinal, renal, respiratory, neurological) or significant disease or
disorder that would interfere with the patient*s safety or ability to
participate in the study • Active infection with human immunodeficiency virus
(HIV) or hepatitis B virus (HBV) or hepatitis C virus (HCV) • History of
abnormal hepatic function (AST > 2×ULN, ALT > 2×ULN, or total bilirubin >
1.5×ULN) • History of abnormal renal function (eGFR CKD-EPI < 60 mL/min/1.73
m2) • History of alcohol or drug abuse within the previous year, or current
evidence of substance dependence or abuse (self-reported alcoholic intake >
three drinks/day) • History of documented severe hypersensitivity to any
medicinal product • Participation in any investigational drug study within five
half-lives of study drug at enrolment • Regular use of corticosteroids,
antihistamines, narcotics, and other pain relief medications for acute
angioedema attack treatment • Use of concomitant medication that are moderate
or potent inhibitors/inducers of CYP3A4 or are metabolized by CYP3A4 and have a
narrow therapeutic range, such as clarithromycin, erythromycin, diltiazem,
itraconazole, ketoconazole, ritonavir, verapamil, goldenseal and grapefruit as
well as phenobarbital, phenytoin, rifampicin, St. John's Wort, and
glucocorticoids (not for topical use or inhalation)