Study to Evaluate the Efficacy and Safety of Deucrictibant for Prophylactic and On-demand Treatment of Angioedema Attacks in Adults with Acquired Angioedema

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pharvaris Netherlands B.V.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

23 Apr 2026 → ongoing

Decision date (initial)

2026-03-22

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Pharvaris Netherlands BV

External identifiers

EU CT number

2025-522051-26-00

WHO UTN

U1111-1326-6056

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Prophylaxis, Pharmacokinetic, Safety, Therapy

Part 1 (Prophylaxis, Double-blind Treatment Phase):
· To evaluate the efficacy of deucrictibant extended-release (XR) tablet compared with
placebo for prophylaxis against angioedema attacks in acquired angioedema due to
C1 inhibitor deficiency (AAE-C1INH)
Part 2 (On-demand, Double-blind Treatment Phase):
· To evaluate the efficacy of deucrictibant soft capsule compared with placebo as
on-demand treatment on the time to symptom relief during angioedema attacks in
AAE-C1INH
Part 3 (On-demand, Open-label Extension Treatment Phase):
· To evaluate the safety and tolerability of deucrictibant soft capsule for on-demand
treatment of angioedema attacks in AAE-C1INH

Secondary objectives 8

1. 1. Part 1 To characterize the efficacy of deucrictibant XR tablet in prophylactic treatment of AAE-C1INH
2. 2. Part 1 To evaluate the safety and tolerability of deucrictibant XR tablet in prophylactic treatment of AAE-C1INH ·
3. 3. Part 1 To evaluate the pharmacokinetics (PK) of deucrictibant XR tablet in prophylactic treatment of AAE-C1INH
4. 4. Part 1 To evaluate the impact on health-related quality of life (HRQoL) and disease control of deucrictibant XR tablet in prophylactic treatment of AAE-C1INH
5. 1. Part 2 To characterize the efficacy of deucrictibant soft capsule compared with placebo as on-demand treatment on symptom relief and resolution of AAE-C1INH attacks
6. 2. Part 2 To evaluate the safety and tolerability of deucrictibant soft capsule compared with placebo for on-demand treatment of AAE-C1INH attacks
7. 3. Part 2 To evaluate the single-dose PK of deucrictibant soft capsule administered in a non-attack state
8. 1. Part 3 To characterize the efficacy of deucrictibant soft capsule as on-demand treatment in achieving symptom relief and resolution of AAE-C1INH attacks

Conditions and MedDRA coding

Acquired Angioedema due to C1 Inhibitor Deficiency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Provision of written informed consent
2. 2. Male or female (sex at birth) aged ≥18 years at the time of providing written informed consent
3. 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.
4. 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.
5. 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.
6. 6. Participant is assessed by the Investigator to have reliable access and ability to use available therapy to effectively manage AAE-C1INH attacks
7. 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
8. 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 13

1. 1. Any concomitant diagnosis of recurrent angioedema other than AAE-C1INH
2. 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).
3. 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.
4. 4. Any females who are pregnant, plan to become pregnant, or are currently breast-feeding
5. 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.
6. 6. Moderate or severe renal impairment (estimated glomerular filtration rate [eGFR calculated by CKD-EPI formula] <60 mL/min/1.73 m2 )
7. 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.
8. 8. History of epilepsy and/or other significant neurological diseases
9. 9. Any clinically significant and uncontrolled gastrointestinal dysfunction (eg, chronic diarrhea, inflammatory bowel disease) that may impact study drug absorption
10. 10. Evidence of current alcohol or drug abuse
11. 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
12. 12. Known hypersensitivity to deucrictibant or any of the excipients of the study drug
13. 13. Use of angiotensin-converting enzyme inhibitors or any estrogen-containing medications with systemic absorption within 5 half-lives before the Screening Visit

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. 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)
2. 2. Part 2 Time to symptom relief defined as PGI-C rating of at least ‘better’ sustained within 12 hours post-treatment
3. 3. Part 3 Incidence of TEAEs, treatment- emergent AESIs, and SAEs
4. 4. Part 3 Change from baseline in clinical laboratory, vital sign, physical examination, and electrocardiogram (ECG) parameters

Secondary endpoints 26

1. 1. Part 1 Proportion of participants who are AAE-C1INH attack-free during the 12-week Prophylaxis Treatment Phase
2. 2. Part 1 Time-normalized number of Investigator-confirmed AAE-C1INH attacks treated with on-demand medication during the 12-week Prophylaxis Treatment Phase
3. 3. Part 1 Time-normalized number of Investigator-confirmed moderate or severe AAE-C1INH attacks during the 12-week Prophylaxis Treatment Phase
4. 4. Part 1 Time-normalized number of Investigator-confirmed severe AAE-C1INH attacks during the 12-week Prophylaxis Treatment Phase
5. 5. Part 1 Proportion of participants achieving ≥50% reduction in AAE-C1INH attack rate relative to baseline during the 12-week Prophylaxis Treatment Phase
6. 6. Part 1 Proportion of participants achieving ≥70% reduction in AAE-C1INH attack rate relative to baseline during the 12-week Prophylaxis Treatment Phase
7. 7. Part 1 Proportion of participants achieving ≥90% reduction in AAE-C1INH attack rate relative to baseline during the 12-week Prophylaxis Treatment Phase
8. 8. Part 1 Incidence of TEAEs, treatment-emergent AESIs, and SAEs
9. 9. Part 1 Change from baseline in clinical laboratory, vital sign, physical examination, and ECG parameters
10. 10. Part 1 Deucrictibant and deucrictibant metabolites pre-dose plasma concentrations at Week 6 and Week 12
11. 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
12. 12. Part 1 Change from baseline in Angioedema Control Test 4-week version (AECT-4wk) at Week 12
13. 13. Part 1 Patient Global Assessment-Change (PGA-C) at Week 12 compared with Patient Global Assessment-Status (PGA-S) at baseline
14. 14. Part 1 Change from baseline in EuroQol 5 Dimension 5 Level (EQ-5D-5L) at Week 12
15. 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
16. 2. Part 2 Time to symptom relief defined as PGI-S rating of at least 1 point reduction sustained within 12 hours post-treatment
17. 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
18. 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
19. 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
20. 6. Part 2 Incidence of TEAEs, treatment-emergent AESIs, and SAEs
21. 7. Part 2 Change from baseline in clinical laboratory, vital sign, physical examination, and ECG parameters
22. 8. Part 2 Deucrictibant and deucrictibant metabolites plasma concentration-time profiles
23. 1. Part 3 Time to symptom relief, defined as PGI-C rating of at least “better” sustained within 12 hours post-treatment
24. 2. Part 3 Time to symptom relief, defined as PGI-S rating of at least 1 point reduction sustained within 12 hours post-treatment
25. 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
26. 15. Part 1 Deucrictibant and deucrictibant metabolites urine concentrations at Week 12

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pharvaris Netherlands B.V.

Sponsor organisation

Pharvaris Netherlands B.V.

Address

J.H. Oortweg 21

City

Leiden

Postcode

2333 CH

Country

Netherlands

Scientific contact point

Organisation

Pharvaris Netherlands B.V.

Contact name

Pharvaris Clinical

Public contact point

Organisation

Pharvaris Netherlands B.V.

Contact name

Pharvaris Clinical

Third parties 17

Locations

9 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 89 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications