CHAPTER-4 – A long term trial of deucrictibant treatment in prophylaxis against HAE attacks in adults and adolescents

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pharvaris Netherlands B.V.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

28 Mar 2025 → ongoing

Decision date (initial)

2025-03-10

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Pharvaris Netherlands B.V.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety, Prophylaxis

To evaluate the safety and tolerability of deucrictibant 40 mg extended-release (XR) tablet in long-term prophylactic treatment of hereditary angioedema (HAE)

Secondary objectives 3

1. To evaluate the efficacy of deucrictibant 40 mg XR tablet in long-term prophylactic treatment of HAE
2. To evaluate the impact on health-related quality of life (HRQoL) of deucrictibant 40 mg XR tablet in long-term prophylactic treatment of HAE
3. To evaluate the pharmacokinetics (PK) of deucrictibant 40 mg XR tablet in long-term prophylactic treatment of HAE

Conditions and MedDRA coding

Hereditary Angioedema

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003090-PIP02-22

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Provision of written informed consent. At the time of signing informed consent, male and female participants must be aged ≥12 years. If the participant is an adolescent (ie, aged ≥12 to <18 years or as determined by local law, ≥40 kg), written assent will be obtained from the participant and consent will be obtained from the participant’s parent/legal guardian. A participant who is an adolescent will sign the informed consent form if they reach the age of 18 or as determined by local law during their participation in the study
2. Participants who previously participated in HAE studies with deucrictibant on-demand or prophylactic treatment may be eligible to be screened for this study. Participants in Study PHA022121-305 must have completed all study drug treatment and assessments in the double-blind Treatment Period of the previous study
3. Participants who have not previously had their HAE diagnosis confirmed by a central laboratory in a Pharvaris-sponsored study with deucrictibant must meet the following requirements: a. Diagnosis of HAE based upon all of the following: • Documented clinical history consistent with HAE (cutaneous or submucosal, nonpruritic swelling without accompanying urticaria) • At least one of the following: 1. Age at reported onset of first angioedema symptoms ≤30 years 2. Family history consistent with HAE 3. C1q within normal range b. Diagnostic testing results to confirm HAE: • C1 esterase inhibitor (C1INH) functional level <50% of the normal level must be shown by chromogenic assay performed by the central laboratory as part of the Screening procedures.
4. For Non rollover participants: History of at least 1 attack in the last 3 consecutive months prior to Screening
5. Participant is assessed by the Investigator to have reliable access and ability to use standard of care on-demand treatments to effectively manage acute HAE attacks
6. Investigator considers that the participant (and parent/caregiver for adolescent participants) is willing and able to adhere to all protocol requirements, including the participant being capable of and compliant with data recording into an eDiary
7. Female participants of childbearing potential (or who become of childbearing potential during the study) must agree to the protocol specified pregnancy testing and use an acceptable contraception method defined in the protocol from enrollment until 30 days after the last study drug administration

Exclusion criteria 14

1. Any diagnosis of angioedema other than HAE
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 ICF signature (whichever was longer) or prior gene therapy for any indication at any time
3. Participants who discontinued from previous studies with deucrictibant prophylactic and/or on demand treatment due to safety reasons or compliance issues that, in the opinion of the Investigator, would interfere with the participant’s safety or compliance to participate in the study. Participants who previously received deucrictibant prophylactic and/or on-demand treatment and recently completed a pregnancy may be eligible to participate in this study. Participants may be eligible for this study if the previous study with deucrictibant prophylactic and/or on-demand treatment has been terminated by the Sponsor prior to their completion of the study
4. Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption (such as oral contraceptives or hormonal replacement therapy) within 4 weeks of Screening
5. For Rollover participants who have completed participation in studies with deucrictibant prophylactic treatment prior to Screening and Non rollover participants: Receiving prophylactic treatment for HAE within the time periods before Screening as indicated below: a. Long-term prophylactic therapy for HAE (C1INH, oral kallikrein inhibitors, or anti-fibrinolytics) within 2 weeks prior to Screening b. Long-term prophylactic therapy for HAE with attenuated androgens within 4 weeks prior to Screening c. Long-term prophylactic monoclonal antibody therapy for HAE (ie, lanadelumab) within 5 half-lives prior to Screening d. Short-term prophylaxis for HAE within 7 days prior to Screening
6. Any females who are pregnant, plan to become pregnant, or are currently breast-feeding
7. 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 Child-Pugh Scoring System. Participants with Gilbert’s syndrome, defined as isolated increase of total bilirubin ≤3× ULN and AST and ALT within the normal range, are not excluded
8. Moderate to severe renal impairment (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2)
9. Any clinically significant history of angina, myocardial infarction, syncope, stroke, left ventricular hypertrophy or cardiomyopathy, uncontrolled hypertension, bradycardia, or any other clinically significant cardiovascular abnormality within the previous year that, in the opinion of the Investigator, would interfere with the participant's safety or ability to participate in the study
10. History of epilepsy and/or other significant neurological diseases
11. Any clinically significant and uncontrolled gastrointestinal dysfunction (eg, chronic diarrhea, inflammatory bowel disease) which impacts study drug absorption
12. History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse
13. 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) of the time of enrollment
14. Known hypersensitivity to deucrictibant or any of the excipients of study drug

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), adverse events of special interest (AESIs), and TEAEs leading to study drug discontinuation
2. Clinical laboratory tests
3. Vital signs
4. Electrocardiogram (ECG) parameters

Secondary endpoints 11

1. Time-normalized (per 4 weeks) number of Investigator-confirmed HAE attacks during the Treatment Period
2. Time-normalized number of Investigator-confirmed HAE attacks treated with on-demand medication during the Treatment Period
3. Time-normalized number of Investigator-confirmed moderate or severe HAE attacks during Treatment Period
4. Time-normalized number of Investigator-confirmed severe HAE attacks during the Treatment Period
5. Proportion of time without angioedema symptoms during the Treatment Period
6. Angioedema Quality of Life (AE-QoL) questionnaire
7. Patient Global Assessment of Change (PGA-Change)
8. Angioedema Control Test 4-week version (AECT-4wk)
9. Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP)
10. Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9)
11. Deucrictibant plasma concentration pre-dose (Ctrough)

Investigational products

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

Test 1

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

Clinical Trials Information

Public contact point

Organisation

Pharvaris Netherlands B.V.

Contact name

Clinical Trials Information

Third parties 7

Locations

11 EU/EEA countries · 32 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 131 files

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

Application history

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