A Phase II, double-blind, placebo-controlled, randomized, cross-over, dose-ranging study of oral PHA-022121 for acute treatment of angioedema attacks in patients with hereditary angioedema due to C1-inhibitor deficiency type I and II
- Conditions
- C1 esterase inhibitor deficiencyhereditary angioedema1004078910002426
- Registration Number
- NL-OMON55154
- Lead Sponsor
- Pharvaris Netherlands BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 2
1. Provision of signed and dated informed consent form
2. Male or female, aged >= 18 and <= 75 years at enrollment
3. Diagnosis of HAE (type I or II) based upon all of the following:
a. Documented clinical history consistent with HAE (subcutaneous or mucosal,
nonpruritic swelling without accompanying urticaria)
b. At least one of the following:
* Age at reported onset of first angioedema symptoms <= 30 years
* Family history consistent with HAE type I or II
* C1q within normal range
c. Diagnostic testing results to confirm HAE type I or II:
* C1-INH functional level < 50% of the normal level
The diagnosis may be established by local laboratory values documented in the
medical records or by genotyping of the C1-INH gene (SERPING1). Before entering
Part II of the study (home treatment), the diagnosis needs to be confirmed by a
central laboratory assessment or by genotyping of the C1-INH gene (SERPING1).
4. Documented history of at least two moderate to severe attacks in the last 4
months, or at least two HAE attacks in the last 2 months prior to screening.
5. Reliable access and experience to use standard of care treatment to
effectively manage acute HAE attacks
6. Capable to record PRO data using the ePRO device
7. Female patients of childbearing potential must agree to be abstinent or to
use highly effective forms of contraception methods from enrollment until 30
days after the last study drug administration. 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 during the study and for 90 days after the last
administration of study drug. In addition, they must agree to not donate sperm
during study participation and within 90 days after the last study drug
administration.
1. Pregnant or breast-feeding
2. Clinically significant abnormal ECG, most notably a QTcF > 470 ms (for
women) or > 450 ms (for men)
3. Any clinically significant history of angina, myocardial infarction,
syncope, stroke, left ventricular hypertrophy or cardiomyopathy, uncontrolled
arterial hypertension (systolic blood pressure > 140 mmHg or diastolic blood
pressure > 90 mmhg), bradycardia (<50bpm), or any other cardiovascular
abnormality within the previous year
4. 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
5. Use of:
a. long-term prophylactic therapy for HAE (C1-INH, oral kallikrein inhibitors,
attenuated androgens, or anti-fibrinolytics) within 2 weeks prior to enrollment
b. long-term prophylactic monoclonal therapy for HAE (e.g., lanadelumab) within
12 weeks prior to enrollment
c. acute C1-INH treatment or short-term prophylaxis for HAE within 7 days prior
to screening. Short-term prophylaxis is defined as C1-INH, attenuated
androgens, or antifibrinolytics to avoid angioedema complications from
medically indicated procedures.
Patients who receive long-term prophylactic treatment for HAE are not eligible
for the study. Patients who have previously stopped long-term prophylactic HAE
treatment because of intolerance or lack of efficacy can enter the study with a
sufficiently long wash-out period as defined above for the different drugs.
6. Positive serology for human immunodeficiency virus (HIV) or active infection
with hepatitis B virus (HBV) or hepatitis C virus (HCV)
7. Abnormal hepatic function (AST > 2×ULN, ALT > 2×ULN, or total bilirubin >
1.5×ULN)
8. Abnormal renal function (eGFR CKD-EPI < 60 mL/min/1.73 m2)
9. 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)
10. History of severe hypersensitivity to any medicinal product
11. 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)
12. Regular use of corticosteroids, antihistamines, narcotics, and other pain
relief medications for acute HAE attack treatment
13. 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)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To evaluate the efficacy of three different single doses of PHA-022121 versus<br /><br>placebo in achieving angioedema symptom reduction defined as change of VAS-3<br /><br>score during acute attacks in patients with hereditary angioedema (HAE) type<br /><br>I/II</p><br>
- Secondary Outcome Measures
Name Time Method