DEUCRICTIBANT for Acquired angioedema due to C1 inhibitor deficiency

Inclusion criteria

• {"criterion_text":"- 1. Provision of written informed consent\n- 2. Male or female (sex at birth) aged ≥18 years at the time of providing written informed consent\n- 3. Diagnosis of AAE-C1INH based upon all of the following: a. Documented clinical history consistent with AAE-C1INH (subcutaneous or mucosal, nonpruritic swelling without accompanying urticaria) b. Diagnostic testing results to confirm AAE-C1INH: - C1INH functional level <40%, as demonstrated by chromogenic assay performed by the central laboratory as part of the screening procedures c. Absence of family history of angioedema d. At least 1 of the following: - C1q performed by the central laboratory is below the lower limit of the normal range - Documented positive anti-C1INH autoantibody test result within 6 months before the Screening Visit Note: If applicable, the confirmatory C1INH functional testing should be performed at least 5 half-lives after the last dose of C1INH therapy.\n- 4. AAE-C1INH Attacks Requirement a. Participants enrolling in Part 1 must have a history of AAE-C1INH Attacks b. New deucrictibant treatment-naïve participants enrolling directly into Part 2 must have a history of at least 2 AAE-C1INH attacks within 12 consecutive weeks prior to the Screening Visit.\n- 5. Participants enrolling in Part 1 must have stable underlying disease of AAE-C1INH, if diagnosed, defined as: a. Lymphoproliferative disease: Participant did not receive chemotherapy or immunotherapy in the 6 months before the Screening Visit. b. Immune complex disorders or monoclonal gammopathy of undetermined significance: Participant did not receive specific treatment (eg, rituximab) in the 6 months before the Screening Visit. c. Other diseases (eg, Systemic Lupus Erythematosus): Maintenance treatment should be stable for at least 6 months before the Screening Visit. In addition, the underlying condition can reasonably be expected to remain stable for the duration of Part 1 of the study in the opinion of the Investigator. This inclusion criterion is not applicable for new deucrictibant treatment-naïve participants enrolling directly into Part 2.\n- 6. Participant is assessed by the Investigator to have reliable access and ability to use available therapy to effectively manage AAE-C1INH attacks\n- 7. Female participants of childbearing potential must agree to the protocol-specified pregnancy testing and to be abstinent from heterosexual intercourse or to use an acceptable contraception method from enrollment until 30 days after the last study drug administration. There are no contraceptive requirements for male participants. Females of non-childbearing potential, defined as prepubertal, surgically sterile (status after hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or postmenopausal (defined as no menses for at least 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) test result indicative of postmenopausal status) do not require contraception during the study\n- 8. Capable of recording, without assistance, eDiary and ePRO data using an electronic device, as evidenced by the eDiary and ePRO training conducted during the Screening Period and upon entry/rollover to Part 2 and Part 3, as applicable"}

Exclusion criteria

• {"criterion_text":"- 1. Any concomitant diagnosis of recurrent angioedema other than AAE-C1INH\n- 10. Evidence of current alcohol or drug abuse\n- 11. Use of concomitant medications with systemic absorption and foods that are moderate and strong inhibitors of cytochrome P450 (CYP) 3A4, such as clarithromycin, erythromycin, diltiazem, itraconazole, ketoconazole, ritonavir, verapamil, and grapefruit juice or strong inducers of CYP3A4 such as carbamazepine, phenytoin, and rifampin within the last 30 days or within 5 half-lives (whichever is longer) at the time of the Screening Visit\n- 12. Known hypersensitivity to deucrictibant or any of the excipients of the study drug\n- 13. Use of angiotensin-converting enzyme inhibitors or any estrogen-containing medications with systemic absorption within 5 half-lives before the Screening Visit\n- 2. Participation in a clinical study with any other investigational drug within the last 30 days or within 5 half-lives of the investigational drug at the Screening Visit (whichever is longer).\n- 3. Participants who have previously received prophylactic therapy but have stopped can participate in this study provided the last dose of the treatment was received prior to the timepoint before the Screening Visit indicated below: a. LTP therapy for AAE-C1INH (C1INH, oral kallikrein inhibitors, or anti-fibrinolytics) within 2 weeks prior to the Screening Visit b. LTP therapy for AAE-C1INH with attenuated androgens within 4 weeks prior to the Screening Visit c. LTP monoclonal antibody therapy for AAE-C1INH (ie, lanadelumab) within 10 weeks prior to the Screening Visit d. Short-term prophylaxis for AAE-C1INH within 1 week prior to the Screening Visit. Short-term prophylaxis is defined as intravenous C1INH, or attenuated androgens to avoid angioedema complications from medically indicated procedures Note: In case of prophylactic treatments not listed above, please consult with the Sponsor. Participants who are receiving LTP treatment for AAE-C1INH and are satisfied with this treatment are not eligible for this study. This exclusion criterion is not applicable to participants enrolling directly into Part 2.\n- 4. Any females who are pregnant, plan to become pregnant, or are currently breast-feeding\n- 5. Abnormal hepatic function (aspartate aminotransferase [AST] >2× upper limit of normal [ULN], alanine aminotransferase [ALT] >2× ULN, or total bilirubin >1.5× ULN or any hepatic impairment via the Child-Pugh Scoring System), or history of clinically significant abnormal hepatic function. Participants with Gilbert’s syndrome, defined as an isolated increase of total bilirubin ≤3× ULN and AST and ALT within the normal range, are not excluded.\n- 6. Moderate or severe renal impairment (estimated glomerular filtration rate [eGFR calculated by CKD-EPI formula] <60 mL/min/1.73 m2 )\n- 7. Any current clinically significant cardiovascular disease (eg, angina, myocardial infarction, syncope, stroke, left ventricular hypertrophy or cardiomyopathy, uncontrolled hypertension, bradycardia, or any other clinically significant cardiovascular abnormality) that, in the opinion of the Investigator, would interfere with the participant's safety or ability to participate in the study.\n- 8. History of epilepsy and/or other significant neurological diseases\n- 9. Any clinically significant and uncontrolled gastrointestinal dysfunction (eg, chronic diarrhea, inflammatory bowel disease) that may impact study drug absorption"}

Primary endpoints

• {"endpoint_text":"- 1. Part 1 Time-normalized (per 4 weeks) number of Investigator-confirmed AAE-C1INH attacks during the 12-week Prophylaxis Treatment Phase (Day 1 through Day 84)","definition_or_measurement_approach":"Time-normalized (per 4 weeks) count of Investigator-confirmed AAE-C1INH attacks occurring during the 12-week prophylaxis treatment phase (Day 1 to Day 84); attacks must be confirmed by Investigator; normalized to per-4-week rate."}
• {"endpoint_text":"- 2. Part 2 Time to symptom relief defined as PGI-C rating of at least ‘better’ sustained within 12 hours post-treatment","definition_or_measurement_approach":"Time from treatment to first Patient Global Impression of Change (PGI-C) rating of at least 'better' that is sustained within 12 hours post-treatment."}
• {"endpoint_text":"- 3. Part 3 Incidence of TEAEs, treatment- emergent AESIs, and SAEs","definition_or_measurement_approach":"Incidence (frequency) of treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs) emerging during treatment, and serious adverse events (SAEs) during the Part 3 open-label extension."}
• {"endpoint_text":"- 4. Part 3 Change from baseline in clinical laboratory, vital sign, physical examination, and electrocardiogram (ECG) parameters","definition_or_measurement_approach":"Change from baseline for clinical laboratory values, vital signs, physical exam findings and ECG parameters measured at scheduled visits during Part 3."}

Secondary endpoints

• {"endpoint_text":"- 1. Part 1 Proportion of participants who are AAE-C1INH attack-free during the 12-week Prophylaxis Treatment Phase","definition_or_measurement_approach":"Proportion of participants with zero Investigator-confirmed AAE-C1INH attacks during Day 1 through Day 84 (12-week prophylaxis phase)."}
• {"endpoint_text":"- 2. Part 1 Time-normalized number of Investigator-confirmed AAE-C1INH attacks treated with on-demand medication during the 12-week Prophylaxis Treatment Phase","definition_or_measurement_approach":"Time-normalized (per 4 weeks) count of Investigator-confirmed AAE-C1INH attacks during the 12-week prophylaxis phase that required on-demand medication."}
• {"endpoint_text":"- 3. Part 1 Time-normalized number of Investigator-confirmed moderate or severe AAE-C1INH attacks during the 12-week Prophylaxis Treatment Phase","definition_or_measurement_approach":"Time-normalized (per 4 weeks) count of Investigator-confirmed attacks categorized as moderate or severe during the 12-week prophylaxis phase."}
• {"endpoint_text":"- 4. Part 1 Time-normalized number of Investigator-confirmed severe AAE-C1INH attacks during the 12-week Prophylaxis Treatment Phase","definition_or_measurement_approach":"Time-normalized (per 4 weeks) count of Investigator-confirmed severe attacks during the 12-week prophylaxis phase."}
• {"endpoint_text":"- 5. Part 1 Proportion of participants achieving ≥50% reduction in AAE-C1INH attack rate relative to baseline during the 12-week Prophylaxis Treatment Phase","definition_or_measurement_approach":"Proportion of participants whose attack rate during the 12-week prophylaxis phase is reduced by ≥50% versus baseline period (as pre-specified)."}
• {"endpoint_text":"- 6. Part 1 Proportion of participants achieving ≥70% reduction in AAE-C1INH attack rate relative to baseline during the 12-week Prophylaxis Treatment Phase","definition_or_measurement_approach":"Proportion of participants with ≥70% reduction in attack rate during the 12-week prophylaxis phase versus baseline."}
• {"endpoint_text":"- 7. Part 1 Proportion of participants achieving ≥90% reduction in AAE-C1INH attack rate relative to baseline during the 12-week Prophylaxis Treatment Phase","definition_or_measurement_approach":"Proportion of participants with ≥90% reduction in attack rate during the 12-week prophylaxis phase versus baseline."}
• {"endpoint_text":"- 8. Part 1 Incidence of TEAEs, treatment-emergent AESIs, and SAEs","definition_or_measurement_approach":"Incidence (frequency) of TEAEs, treatment-emergent AESIs and SAEs during Part 1."}
• {"endpoint_text":"- 9. Part 1 Change from baseline in clinical laboratory, vital sign, physical examination, and ECG parameters","definition_or_measurement_approach":"Change from baseline for labs, vitals, physical exam and ECG parameters measured at scheduled visits in Part 1."}
• {"endpoint_text":"- 10. Part 1 Deucrictibant and deucrictibant metabolites pre-dose plasma concentrations at Week 6 and Week 12","definition_or_measurement_approach":"Pre-dose (trough) plasma concentrations of deucrictibant and metabolites measured at Week 6 and Week 12."}
• {"endpoint_text":"- 11. Part 1 Change from baseline in Angioedema Quality of Life (AE-QoL) total score, functioning domain score, and fears/shame domain score at Weeks 4, 8, and 12","definition_or_measurement_approach":"Change from baseline in AE-QoL total score and domain scores (functioning, fears/shame) at Weeks 4, 8 and 12."}
• {"endpoint_text":"- 12. Part 1 Change from baseline in Angioedema Control Test 4-week version (AECT-4wk) at Week 12","definition_or_measurement_approach":"Change from baseline in AECT-4wk score measured at Week 12."}
• {"endpoint_text":"- 13. Part 1 Patient Global Assessment-Change (PGA-C) at Week 12 compared with Patient Global Assessment-Status (PGA-S) at baseline","definition_or_measurement_approach":"Patient Global Assessment of Change (PGA-C) at Week 12 compared to baseline PGA-Status (PGA-S)."}
• {"endpoint_text":"- 14. Part 1 Change from baseline in EuroQol 5 Dimension 5 Level (EQ-5D-5L) at Week 12","definition_or_measurement_approach":"Change from baseline in EQ-5D-5L measured at Week 12."}
• {"endpoint_text":"- 1. Part 2 Time to complete symptom resolution, defined as achieving Patient Global Impression of Severity (PGI-S) rating of “no symptoms” sustained within 24 hours post-treatment","definition_or_measurement_approach":"Time from treatment to PGI-S rating of 'no symptoms' sustained within 24 hours post-treatment."}
• {"endpoint_text":"- 2. Part 2 Time to symptom relief defined as PGI-S rating of at least 1 point reduction sustained within 12 hours post-treatment","definition_or_measurement_approach":"Time from treatment to ≥1 point reduction in PGI-S score sustained within 12 hours post-treatment."}
• {"endpoint_text":"- 3. Part 2 Proportion of study drug-treated attacks achieving complete symptom resolution, defined as achieving PGI-S rating of “no symptoms” at 24 hours post-treatment","definition_or_measurement_approach":"Proportion of treated attacks achieving PGI-S 'no symptoms' at 24 hours post-treatment."}
• {"endpoint_text":"- 4. Part 2 Time to onset of symptom relief, defined as PGI-C rating of at least “a little better” sustained within 12 hours post-treatment","definition_or_measurement_approach":"Time to first PGI-C rating of at least 'a little better' sustained within 12 hours post-treatment."}
• {"endpoint_text":"- 5. Part 2 Time to End of Progression (EoP) in attack symptoms within 12 hours, with EoP time defined as the earliest post-treatment timepoint after which all subsequent PGI-C ratings are stable or improved","definition_or_measurement_approach":"Time to End of Progression (EoP): earliest post-treatment timepoint after which all subsequent PGI-C ratings are stable or improved, within 12 hours."}
• {"endpoint_text":"- 6. Part 2 Incidence of TEAEs, treatment-emergent AESIs, and SAEs","definition_or_measurement_approach":"Incidence of TEAEs, treatment-emergent AESIs and SAEs during Part 2."}
• {"endpoint_text":"- 7. Part 2 Change from baseline in clinical laboratory, vital sign, physical examination, and ECG parameters","definition_or_measurement_approach":"Change from baseline in labs, vitals, physical exam and ECG parameters measured during Part 2."}
• {"endpoint_text":"- 8. Part 2 Deucrictibant and deucrictibant metabolites plasma concentration-time profiles","definition_or_measurement_approach":"Plasma concentration versus time profiles for deucrictibant and metabolites following dosing in Part 2."}
• {"endpoint_text":"- 1. Part 3 Time to symptom relief, defined as PGI-C rating of at least “better” sustained within 12 hours post-treatment","definition_or_measurement_approach":"Time to PGI-C rating of at least 'better' sustained within 12 hours post-treatment in Part 3."}
• {"endpoint_text":"- 2. Part 3 Time to symptom relief, defined as PGI-S rating of at least 1 point reduction sustained within 12 hours post-treatment","definition_or_measurement_approach":"Time to ≥1 point reduction in PGI-S sustained within 12 hours post-treatment in Part 3."}
• {"endpoint_text":"- 3. Part 3 Proportion of study drug-treated attacks achieving complete symptom resolution, defined as achieving PGI-S rating of “no symptoms” at 24 hours post-treatment","definition_or_measurement_approach":"Proportion of treated attacks achieving PGI-S 'no symptoms' at 24 hours post-treatment in Part 3."}
• {"endpoint_text":"- 15. Part 1 Deucrictibant and deucrictibant metabolites urine concentrations at Week 12","definition_or_measurement_approach":"Urine concentrations of deucrictibant and metabolites measured at Week 12."}

Methods

• Recruitment materials and arrangements documented: 'K1_Recruitment arrangements' and 'K2_Recruitment material_ParticipantJourney' (participant-facing journey materials) provided to sites (country-specific files exist for DE, FR, BG, IT, NL, PL, ES, AT, etc.).
• Dear Colleague Letter (K2_Recruitment material_DearColleagueLetter) to clinicians/sites (country-specific versions available)
• Study PowerPoint presentation for site/staff use (K2_Recruitment material_StudyPowerpoint)
• Study Reference Card materials for sites (K2_Recruitment material_StudyReferenceCard)
• Recruitment arrangement documents are available per country (files named K1/K2 for country codes DE, FR, BG, IT, NL, PL, ES, AT, HU) indicating country-specific recruitment packs and site materials.

Austria

Earliest CTIS Part Ii Submission Date

06-03-2026

Latest Decision Or Authorization Date

22-03-2026

Processing Time Days

16

Number Of Sites

1

Number Of Participants

1

Bulgaria

Earliest CTIS Part Ii Submission Date

12-03-2026

Latest Decision Or Authorization Date

19-03-2026

Processing Time Days

7

Number Of Sites

1

Number Of Participants

1

France

Earliest CTIS Part Ii Submission Date

16-02-2026

Latest Decision Or Authorization Date

19-03-2026

Processing Time Days

31

Number Of Sites

3

Number Of Participants

3

Germany

Earliest CTIS Part Ii Submission Date

20-02-2026

Latest Decision Or Authorization Date

17-03-2026

Processing Time Days

25

Number Of Sites

3

Number Of Participants

2

Hungary

Earliest CTIS Part Ii Submission Date

19-01-2026

Latest Decision Or Authorization Date

19-03-2026

Processing Time Days

59

Number Of Sites

1

Number Of Participants

1

Italy

Earliest CTIS Part Ii Submission Date

23-02-2026

Latest Decision Or Authorization Date

18-03-2026

Processing Time Days

23

Number Of Sites

7

Number Of Participants

5

Spain

Earliest CTIS Part Ii Submission Date

23-02-2026

Latest Decision Or Authorization Date

18-03-2026

Processing Time Days

23

Number Of Sites

2

Number Of Participants

2

Netherlands

Earliest CTIS Part Ii Submission Date

09-03-2026

Latest Decision Or Authorization Date

19-03-2026

Processing Time Days

10

Number Of Sites

1

Number Of Participants

1

Poland

Earliest CTIS Part Ii Submission Date

18-02-2026

Latest Decision Or Authorization Date

23-03-2026

Processing Time Days

33

Number Of Sites

1

Number Of Participants

2

Primary sponsor

Full Name

Pharvaris Netherlands B.V.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Netherlands

Contract research organisations

Name

Medpace Finland Oy

Responsibilities

codes:1,10,12,13,2,3,4,5,6,7,8,9

Name

Hangzhou Tigermed Consulting Co. Ltd.

Responsibilities

code:10

Name

Phlexglobal Limited

Responsibilities

End of study TMF Migration (CRO to SPONSOR)

Name

Eclinical Solutions LLC

Responsibilities

codes:6,7

Third parties

• {"country":"United States","full_name":"Praxis Communications LLC","duties_or_roles":"Branding","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Austria","full_name":"Attoquant Diagnostics GmbH","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"National Jewish Health","duties_or_roles":"code:4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Belgium","full_name":"A.M.L.","duties_or_roles":"code:4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Switzerland","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"code:14","organisation_type":"Pharmaceutical company"}
• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"codes:1,10,12,13,2,3,4,5,6,7,8,9","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Sprout Health Solutions Limited","duties_or_roles":"Qualitative Interviews","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"code:7","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code:6","organisation_type":"Non-Pharmaceutical company"}
• {"country":"China","full_name":"Hangzhou Tigermed Consulting Co. Ltd.","duties_or_roles":"code:10","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"code:3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Eclinical Solutions LLC","duties_or_roles":"codes:6,7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Unisphere Travel Ltd. Inc.","duties_or_roles":"Patient travel management","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Ardena Bioanalysis B.V.","duties_or_roles":"code:4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Phlexglobal Limited","duties_or_roles":"End of study TMF Migration (CRO to SPONSOR)","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Centre Hospitalier Universitaire Grenoble Alpes","duties_or_roles":"code:4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"MARKEN Germany GmbH","duties_or_roles":"codes:14,15 (IP delivery to patients´ home service)","organisation_type":"Pharmaceutical company"}