A blinded, placebo-controlled and randomized phase 2 study to test different doses of oral PHA-022121 for prophylaxis of angioedema attacks in patients with hereditary angioedema (HAE).
- Conditions
- Hereditary angioedema due to C1-Inhibitor Deficiency (Type I or Type II)MedDRA version: 23.1Level: PTClassification code 10019860Term: Hereditary angioedemaSystem Organ Class: 10010331 - Congenital, familial and genetic disordersMedDRA version: 26.0Level: LLTClassification code 10080960Term: Hereditary angioedema type IISystem Organ Class: 10010331 - Congenital, familial and genetic disordersMedDRA version: 21.0Level: LLTClassification code 10080957Term: Hereditary angioedema C1 inhibitor deficiencySystem Organ Class: 10010331 - Congenital, familial and genetic disordersMedDRA version: 21.0Level: LLTClassification code 10080956Term: Hereditary angioedema type ISystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Body processes [G] - Immune system processes [G12]
- Registration Number
- EUCTR2021-000227-13-AT
- Lead Sponsor
- Pharvaris Netherlands BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 30
Each patient must meet the following criteria to be enrolled in this study. 1. Male or female patients aged = 18 to = 75 years at screening.
2. Diagnosis of HAE (type I or II) based upon all of the following:
a. Documented clinical history consistent with HAE (subcutaneous and/or mucosal swelling without accompanying wheals)
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 should be documented prior to randomization by a local or central laboratory value documented in the medical records.
Note: For patients who receive any form of C1-INH replacement, the last dose before the confirmatory C1-INH testing should be given at least 5half-lives before the date of sampling.
3. Documented history of at least 3 HAE attacks within the last 3 consecutive months prior to screening. If the patient has no documentation or has less than 3 attacks in the 3 months before the screening visit, or was on prophylactic treatment, patient must experience a minimum of 2 HAE attacks during the screening period (up to 8 weeks).
4. Is assessed by the investigator to have reliable access and ability to use standard of care treatments alone to effectively manage acute HAE attacks.
5. Body weight of = 40 kg at screening.
6. Investigator considers that the patient is willing and able to adhere to all protocol requirements, including being capable of and compliant with data recording into an electronic Patient Reported Outcome (ePRO) tool.
7. Female patients of childbearing potential must agree to the protocol specified pregnancy testing and to practice abstinence from heterosexual intercourse in line with the preferred and usual lifestyle of
the patient or to use a medically acceptable form of contraception methods from enrollment until 30 days after the last study drug administration. Methods acceptable for this study include male condom with or without spermicide, cervical cap, diaphragm or sponge with spermicide, a combination of male condom with cap, diaphragm or sponge with spermicide (double-barrier methods), combined or progestin-only hormonal methods (oral, injectable, or implantable), intrauterine device (IUD, all types), intrauterine hormone releasing systems (IUS). Females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal (defined as no menses for at least 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) test result indicative of post-menopausal status) do not require contraception during the study. There are no contraceptive requirements for male patients.
8. The patient has provided informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
Patients who meet any of the following criteria will be excluded from the study.
1. Concomitant diagnosis of another form of chronic, recurrent angioedema, such as acquired angioedema (AAE) with C1-INH deficiency, angioedema with normal C1-INH levels (HAE type III), idiopathic nonhistaminergic angioedema, or recurrent angioedema associated with urticaria.
2. Participation in a clinical trial with any other investigational drug within the last 30 days or within 5 half-lives of IMP at screening (whichever was longer). Previous participation in the Study PHA022121-C201 is permitted.
3. Exposure to angiotensin-converting enzyme (ACE) inhibitors within 4 weeks of screening.
4. Receiving prophylactic treatment for HAE. Patients who have previously received prophylactic therapy but have stopped, can participate in this study provided a sufficiently long washout period is observed before the patient is screened. Exclusion includes use of:
a. long-term prophylactic therapy for HAE (C1-INH, oral kallikrein inhibitors, attenuated androgens, or anti-fibrinolytics) within 2 weeks prior to screening
b. long-term prophylactic monoclonal therapy for HAE (i.e., lanadelumab) within 11 weeks prior to screening
c. short-term prophylaxis for HAE within 7 days prior to screening
Short-term prophylaxis is defined as intravenous C1-INH, attenuated androgens, or antifibrinolytics to avoid angioedema complications from medically indicated procedures.
Note: Patients who are receiving long-term prophylactic treatment for HAE and are satisfied with this treatment, are not eligible for this 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 in Exclusion Criterion #4 for the different HAE therapies.
5. Clinically significant abnormal electrocardiogram (ECG), most notably a QTcF > 470 milliseconds (for women) or > 450 milliseconds (for men).
6. Any clinically significant history of angina, myocardial infarction, syncope, stroke, left ventricular hypertrophy or cardiomyopathy, uncontrolled hypertension (systolic blood pressure > 140 mm Hg or diastolic blood pressure > 90 mm Hg), bradycardia (heart rate < 50 beats per minute) or any other cardiovascular abnormality within the previous year.
7. 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.
8. Any females who are pregnant, plan to become pregnant, or are currently breast-feeding.
9. Abnormal hepatic function (aspartate aminotransferase [AST] > 2×upper limit of normal [ULN], alanine aminotransferase [ALT] > 2×ULN, or total bilirubin > 1.5×ULN). Patients with Gilbert's syndrome, being defined as isolated increase of total bilirubin =3xULN and AST and ALT within the normal range, are not excluded.
10. Abnormal renal function (estimated glomerular filtration rate [eGFR] CKD-EPI < 60 mL/min/1.73 m2).
11. History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse.
12. Use of concomitant medications that are strong inhibitors of CYP3A4 such as clarithromycin, itraconazole, ketoconazole, ritonavir, and grapefruit as well as inducers of CYP3A4 such as phenobarbital, phenytoin, rifampicin, and St. John's Wort.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method