C1 esterase inhibitor deficiency
Conditions
Interventions
The IMP consists of 10 mg PHA-022121 soft capsules and matching placebo soft
capsules for oral use:
• Low dose (10 mg): one capsule of 10 mg PHA-022121 and two placebo capsules
• Medium dose (20 mg)
Sponsors
Pharvaris Netherlands BV
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Provision of signed and dated informed consent form 2. Male or female, aged >= 18 and
Exclusion criteria
Exclusion criteria: 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 ( 2×ULN, ALT > 2×ULN, or total bilirubin > 1.5×ULN) 8. Abnormal renal function (eGFR CKD-EPI 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the efficacy of three different single doses of PHA-022121 versus placebo in achieving angioedema symptom reduction defined as change of VAS-3 score during acute attacks in patients with hereditary angioedema (HAE) type I/II | — |
Secondary
| Measure | Time frame |
|---|---|
| The key secondary objectives of the study are: To further evaluate the clinical efficacy of three different single doses of PHA-022121 versus placebo with regards to • Onset of symptom relief, • The proportion of attacks requiring the use of HAE rescue medication • Time to almost complete and complete symptom relief • Change in MSCS at 4 h post-treatment, • Change in TOS at 4 h post-treatment. Other secondary objectives of the study are: • To evaluate the safety of three different single doses of PHA-022121 versus placebo • To evaluate the pharmacokinetics, dose-effect relationship, and concentration-effect relationship of PHA-022121 • To evaluate the frequency and timing of HAE rescue medication use of three different single doses of PHA-022121 versus placebo • To evaluate the time to onset of primary symptom relief by VAS • To evaluate the change of the individual VAS scores (skin pain, skin swelling, abdominal pain) from pre-treatment to 4 h post-treatment • To evaluate the change of MSCS score at 24 h post-treatment • To evaluate the change of TOS at 24 h post-treatment • To evaluate the TSQM scores at 48 h post-treatment | — |
Countries
Netherlands
Outcome results
None listed