oral PHA-022121 for the acute treatment and prophylaxis Of angioedema attacks in Patients with Acquired C1-Inhibitor Deficiency

Phase 2

Completed

Conditions: Acquired C1-inhibitor deficiency
10027665

Registration Number: NL-OMON51973

Lead Sponsor: Academisch Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 6

Inclusion Criteria

In order to be eligible to participate in this study, a patient must meet all
of the following criteria:
• Provision of signed and dated informed consent form
• Male or female, aged > 35 at enrollment
• Diagnosis of AAE-C1-INH based upon all of the following:
1. Documented clinical history consistent with AAE-C1-INH (subcutaneous or
mucosal, nonpruritic swelling without accompanying urticarial 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 4 months,
or at least two angioedema attacks in the last 2 months.
• Reliable access and experience to use 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 enrollment 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 2
weeks after each administration of study drug. In addition, they must agree to
not donate sperm during study participation.

Exclusion Criteria

Patients who meet any of the following criteria will be excluded from the
study:
• 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 >
3 drinks/day)
• History of documented severe hypersensitivity to any medicinal product
• Participation in any other investigational drug study currently, within the
last 30 days or within 5 half-lives of study drug at enrollment (whichever was
longer)
• 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)
Patients who meet all in- and exclusion criteria but are unable to adhere to
the diary and unforeseen visit requirements of part 1 as determined by the
investigator, may participate in part 2 only.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The main study parameter for part 1 is the change of the 3-symptom composite<br /><br>visual analogue scale (VAS-3) score from pre-treatment to 4 h post-treatment.<br /><br>The main study parameter for part 2 is the number of investigator-confirmed<br /><br>angioedema attacks recorded during the treatment period expressed as the<br /><br>normalized number of attacks per month of exposure.</p><br>

Secondary Outcome Measures