A blinded, placebo-controlled and randomized phase 2 study to test different doses of oral PHA-022121 for acute treatment of angioedema attacks in patients with hereditary angioedema (HAE).

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 - RAPIDe-1

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2020-003445-11-DE

Enrollment

Registered

2021-02-11

Start date

2021-02-26

Completion date

Unknown

Last updated

2024-03-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hereditary angioedema attacks caused by Type 1 and 2 C1-Inhibitor Deficiency MedDRA version: 23.1 Level: PT Classification code 10019860 Term: Hereditary angioedema System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 21.0 Level: LLT Classification code 10080956 Term: Hereditary angioedema type I System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 21.0 Level: LLT Classification code 10080957 Term: Hereditary angioedema

Interventions

Product Name: PHVS416 Product Code: PHA-022121 Pharmaceutical Form: Capsule, soft CAS Number: 2340111-58-0 Current Sponsor code: PHA-022121 Other descriptive name: PHA-022121 Concentration unit: mg mi

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 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 = 40 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 =65 years) yes F.1.3.1 Number of subjects for this age range 14

Exclusion criteria

Exclusion criteria: 1. Pregnant or breast-feeding 2. Clinically significant abnormal ECG, most notably a QTcF > 470 ms (for females) or > 450 ms (for males) 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), with the exception of patients with Gilbert's syndrome. 8. Abnormal renal function (eGFR CKD-EPI 3 drinks/day) 10. History of documented 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, 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
Main Objective: To evaluate the efficacy of three different single doses of PHA-022121 versus placebo in achieving angioedema symptom reduction, defined as change in the 3-symptom composite visual analogue scale (VAS-3) score during acute attacks in patients with hereditary angioedema (HAE) type I/II ;Secondary Objective: Key Objectives: To evaluate the clinical efficacy of 3 different single doses of PHA022121 vs placebo with regards to: •Time to onset of symptom relief by VAS-3 •Time to almost complete or complete symptom relief by VAS-3 •Change in MSCS score at 4h post-treatment •TOS at 4h post-treatment Other: •To evaluate the clinical efficacy of 3 different single doses of PHA022121 vs placebo with regards to: ?Time to onset of primary symptom relief by VAS ?Proportion of IMP-treated attacks requiring use of HAE rescue medication ?Time to first use of HAE rescue medication ?Change in the individual VAS scores (skin, swelling and abdominal pain) from pre to 4h post-treatment ?Change in MSCS score at 24h post-treatment ?TOS at 24h post-treatment •To evaluate the safety of 3 different single doses of PHA-022121 vs placebo •To evaluate the pharmacokinetics, dose-effect relationship and concentration-effect relationship of PHA-022121 •To evaluate TSQM scores at 48h post-treatment ;Primary end point(s): The primary endpoint of the study is the change in the VAS-3 score from pre-treatment to 4 h post-treatment. ;Timepoint(s) of evaluation of this end point: 4h post treatment of an attack during the home treatment phase (Part II).	—

Measure

Time frame

Main Objective: To evaluate the efficacy of three different single doses of PHA-022121 versus placebo in achieving angioedema symptom reduction, defined as change in the 3-symptom composite visual analogue scale (VAS-3) score during acute attacks in patients with hereditary angioedema (HAE) type I/II ;Secondary Objective: Key Objectives: To evaluate the clinical efficacy of 3 different single doses of PHA022121 vs placebo with regards to: •Time to onset of symptom relief by VAS-3 •Time to almost complete or complete symptom relief by VAS-3 •Change in MSCS score at 4h post-treatment •TOS at 4h post-treatment Other: •To evaluate the clinical efficacy of 3 different single doses of PHA022121 vs placebo with regards to: ?Time to onset of primary symptom relief by VAS ?Proportion of IMP-treated attacks requiring use of HAE rescue medication ?Time to first use of HAE rescue medication ?Change in the individual VAS scores (skin, swelling and abdominal pain) from pre to 4h post-treatment ?Change in MSCS score at 24h post-treatment ?TOS at 24h post-treatment •To evaluate the safety of 3 different single doses of PHA-022121 vs placebo •To evaluate the pharmacokinetics, dose-effect relationship and concentration-effect relationship of PHA-022121 •To evaluate TSQM scores at 48h post-treatment ;Primary end point(s): The primary endpoint of the study is the change in the VAS-3 score from pre-treatment to 4 h post-treatment. ;Timepoint(s) of evaluation of this end point: 4h post treatment of an attack during the home treatment phase (Part II).

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Secondary

Measure	Time frame
Secondary end point(s): The key secondary efficacy endpoints of the study are: •Time to onset of symptom relief, assessed by a = 30 reduction in VAS-3 score from the pre-treatment score. •Time to almost complete and complete symptom relief by VAS-3 score Almost complete symptom relief is defined as all 3 individual VAS scores of the VAS-3 having a value = 10. Complete symptom relief is defined as all 3 individual VAS scores of the VAS-3 having a value of 0. • Time to a =50% reduction in VAS-3 score from the pre-treatment score. • Change in MSCS score from pre-treatment to 4 h post-treatment • TOS at 4 h post-treatment Other secondary efficacy endpoints of the study are as follows: • Time to onset of primary symptom relief assessed by a 30% reduction in the VAS for the primary symptom, and time to a 50% reduction in the VAS for the primary symptom. The symptom (skin swelling, skin pain, or abdominal pain) with the highest pre-treatment VAS score is considered the primary symptom. • Proportion of IMP-treated attacks requiring HAE rescue medication within 12 h, within 24 h, and within 48 h post-treatment • Time to first HAE rescue medication use for IMP treated attacks, if applicable. An IMP-treated attack refers to an attack treated with blinded IMP (study drug). • Change in the VAS score for individual symptoms (skin pain, skin swelling, abdominal pain) from pre-treatment to 4 h post-treatment •Change in MSCS score from pre-treatment to 24 h post-treatment • TOS at 24 h post-treatment • TSQM scores at 48 h post-treatment The safety endpoints of the study are: • Treatment-emergent adverse events (TEAEs), treatment-related TEAEs, and treatment-emergent serious adverse events (TESAEs), and treatment-related TESAEs • Clinical laboratory tests (chemistry, hematology, coagulation, and urinalysis) • Vital signs • Electrocardiograms (ECGs) ;Timepoint(s) of evaluation of this end point: Safety: All AEs with onset after signing informed consent (including SAEs) are to be	—

Measure

Time frame

Secondary end point(s): The key secondary efficacy endpoints of the study are: •Time to onset of symptom relief, assessed by a = 30 reduction in VAS-3 score from the pre-treatment score. •Time to almost complete and complete symptom relief by VAS-3 score Almost complete symptom relief is defined as all 3 individual VAS scores of the VAS-3 having a value = 10. Complete symptom relief is defined as all 3 individual VAS scores of the VAS-3 having a value of 0. • Time to a =50% reduction in VAS-3 score from the pre-treatment score. • Change in MSCS score from pre-treatment to 4 h post-treatment • TOS at 4 h post-treatment Other secondary efficacy endpoints of the study are as follows: • Time to onset of primary symptom relief assessed by a 30% reduction in the VAS for the primary symptom, and time to a 50% reduction in the VAS for the primary symptom. The symptom (skin swelling, skin pain, or abdominal pain) with the highest pre-treatment VAS score is considered the primary symptom. • Proportion of IMP-treated attacks requiring HAE rescue medication within 12 h, within 24 h, and within 48 h post-treatment • Time to first HAE rescue medication use for IMP treated attacks, if applicable. An IMP-treated attack refers to an attack treated with blinded IMP (study drug). • Change in the VAS score for individual symptoms (skin pain, skin swelling, abdominal pain) from pre-treatment to 4 h post-treatment •Change in MSCS score from pre-treatment to 24 h post-treatment • TOS at 24 h post-treatment • TSQM scores at 48 h post-treatment The safety endpoints of the study are: • Treatment-emergent adverse events (TEAEs), treatment-related TEAEs, and treatment-emergent serious adverse events (TESAEs), and treatment-related TESAEs • Clinical laboratory tests (chemistry, hematology, coagulation, and urinalysis) • Vital signs • Electrocardiograms (ECGs) ;Timepoint(s) of evaluation of this end point: Safety: All AEs with onset after signing informed consent (including SAEs) are to be

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Countries

Belgium, Bulgaria, Canada, Czech Republic, France, Germany, Hungary, Israel, Italy, Netherlands, Poland, Spain, United Kingdom

Contacts

Public ContactPharvaris Clinical

Pharvaris Netherlands BV

clinical@pharvaris.com+31 (0)712036410

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026