DEUCRICTIBANT for Hereditary angioedema

Inclusion criteria

• {"criterion_text":"- Provision of written informed consent. At the time of signing informed consent, male and female participants must be aged ≥12 years. Adolescent participants (ie, aged ≥12 to <18 years or as determined by local law) must also be ≥40 kg in body weight at Screening. If the participant is an adolescent, written assent will be obtained from the participant and consent will be obtained from the participant’s parent/legally designated representative/guardian, per local regulations. A participant who is an adolescent will sign the ICF if they reach the age of 18 years or as determined by local law during their participation in the study.\n- Participants who previously completed Study PHA022121-C306 may be eligible to be screened for this study. For these participants, there is no need to repeat HAE diagnostic test as described in Inclusion Criterion #3 if the C1INH function was confirmed by the central laboratory in Study PHA022121-C306.\n- Diagnosis of HAE type 1/2 or type 3 based on the following: a. For participants with HAE type 1/2: • Documented clinical history consistent with HAE (cutaneous or submucosal, nonpruritic swelling without accompanying urticaria) • At least one of the following: − Age at reported onset of first angioedema symptoms ≤30 years − Family history consistent with HAE − C1q above the lower limit of the normal range by central laboratory as part of the Screening assessments • Diagnostic testing results to confirm HAE: − 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. Participants with functional C1INH level 40% to <50% of the normal level must also have a C4 level below the normal range. b. For participants with HAE type 3: • Recurrent angioedema attacks with diagnostic testing results obtained during Screening to confirm C1INH function ≥50% of normal and C4 level not below the lower level of the normal range performed by the central laboratory • Must meet one of the following: − Documented genetic mutation associated with HAE type 3 as listed in the HAEA and WAO/EAACI Guidelines (Appendix 2) Or − If no documented genetic mutation: - Clinical diagnosis with family history of HAE type 3 and an elevated BK peptide level previously confirmed by a commercially available liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay And - Attacks not responding to treatments with high-dose antihistamine (cetirizine 40 mg/day or equivalent high-dose second-generation antihistamine medication) and no clinical attack symptom relief if treated with corticosteroid, montelukast, or omalizumab • Documented effective attack symptom relief with on-demand icatibant treatment\n- History of at least 3 HAE attacks within the 3 consecutive months prior to Screening Visit\n- Participants must experience at least XX Investigator-confirmed attacks during the up to 8 week Run-in Period\n- 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.\n- Investigator considers that the participant (and parent/legally designated representaive/guardian for adolescent participants) is willing and able to adhere to all protocol requirements, including ensuring that the participant is capable of, and compliant with, eDiary and ePRO data recording\n- Female participants of childbearing potential (or who become of childbearing potential during the study) must agree to the protocol specified pregnancy testing and to be abstinent from heterosexual intercourse or to use a highly effective contraception method as defined in the protocol (Section 8.2.2) and as available locally, from enrollment until 30 days after the last study drug administration."}

Exclusion criteria

• {"criterion_text":"- Any diagnosis of angioedema other than HAE\n- 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\n- History of epilepsy and/or other significant neurological diseases\n- Any clinically significant and uncontrolled gastrointestinal dysfunction (eg, chronic diarrhea, inflammatory bowel disease) which impacts study drug absorption\n- History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse\n- 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 randomization\n- Known hypersensitivity to deucrictibant or any of the excipients of the study drug\n- 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 Screening (whichever was longer)\n- Has received prior prophylactic treatment or on-demand treatment with deucrictibant, with the exception of participants from Study PHA022121-C306\n- 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\n- Prior gene therapy for any indication at any time\n- Receiving prophylactic treatment for HAE and are satisfied with this treatment. Patients who are not satisfied (eg, tolerability issues, lack of efficacy) and have previously stopped long-term prophylactic HAE treatment can sign the ICF and begin the Screening Period only if their last dose of treatment was received prior to the time point before Screening indicated below: a. Long-term prophylactic therapy for HAE (with C1INH, oral kallikrein inhibitors, or anti fibrinolytics): 2 weeks prior to Screening b. Long-term prophylactic therapy for HAE with attenuated androgens: 4 weeks prior to Screening c. Long-term prophylactic monoclonal antibody therapy for HAE (ie, lanadelumab): 5 half-lives prior to Screening d. Short-term prophylaxis for HAE: 7 days prior to Screening Note: Short-term prophylaxis is defined as intravenous (iv) C1INH to avoid angioedema complications from medically indicated procedures\n- Any females who are pregnant, plan to become pregnant, or are currently breast-feeding\n- 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\n- Moderate or severe renal impairment (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2)"}

Primary endpoints

• {"endpoint_text":"- Time-normalized (per 4 weeks) number of Investigator confirmed HAE attacks during the 24 week Treatment Period (Day 1 through Day 168)","definition_or_measurement_approach":"Time-normalized (per 4 weeks) count of Investigator-confirmed hereditary angioedema (HAE) attacks occurring during the 24-week treatment period (Day 1 to Day 168)."}

Secondary endpoints

• {"endpoint_text":"- Time-normalized number of Investigator confirmed HAE attacks treated with on-demand medication during the 24 week Treatment Period","definition_or_measurement_approach":"Time-normalized count of Investigator-confirmed HAE attacks that were treated with on-demand medication during the 24-week treatment period."}
• {"endpoint_text":"- Time-normalized number of Investigator confirmed moderate or severe HAE attacks during the 24 week Treatment Period","definition_or_measurement_approach":"Time-normalized count of Investigator-confirmed moderate or severe HAE attacks during the 24-week treatment period."}
• {"endpoint_text":"- Time-normalized number of Investigator confirmed severe HAE attacks during the 24 week Treatment Period","definition_or_measurement_approach":"Time-normalized count of Investigator-confirmed severe HAE attacks during the 24-week treatment period."}
• {"endpoint_text":"- Proportion of participants achieving ≥50% reduction in HAE attack rate relative to baseline during the 24 week Treatment Period","definition_or_measurement_approach":"Proportion of participants with a ≥50% reduction in HAE attack rate versus baseline over the 24-week treatment period."}
• {"endpoint_text":"- Proportion of participants achieving ≥70% reduction in HAE attack rate relative to baseline during the 24 week Treatment Period","definition_or_measurement_approach":"Proportion of participants with a ≥70% reduction in HAE attack rate versus baseline over the 24-week treatment period."}
• {"endpoint_text":"- Proportion of participants achieving ≥90% reduction in HAE attack rate relative to baseline during the 24 week Treatment Period","definition_or_measurement_approach":"Proportion of participants with a ≥90% reduction in HAE attack rate versus baseline over the 24-week treatment period."}
• {"endpoint_text":"- Proportion of participants that are HAE attack-free during the 24 week Treatment Period","definition_or_measurement_approach":"Proportion of participants with zero HAE attacks during the 24-week treatment period."}
• {"endpoint_text":"- Proportion of time without angioedema symptoms during the 24 week Treatment Period","definition_or_measurement_approach":"Proportion of the 24-week treatment period during which participants report no angioedema symptoms."}
• {"endpoint_text":"- Treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs), adverse events of special interest (AESIs), and TEAEs leading to study drug discontinuation","definition_or_measurement_approach":"Safety assessment via recording of TEAEs, SAEs, AESIs and TEAEs resulting in study drug discontinuation during study treatment."}
• {"endpoint_text":"- Changes in clinical laboratory tests from baseline","definition_or_measurement_approach":"Laboratory safety assessments comparing on-treatment values to baseline."}
• {"endpoint_text":"- Changes in vital signs from baseline","definition_or_measurement_approach":"Vital sign measurements (e.g., BP, HR) compared to baseline."}
• {"endpoint_text":"- Changes in electrocardiogram (ECG) parameters from baseline","definition_or_measurement_approach":"ECG parameter comparisons to baseline."}
• {"endpoint_text":"- Deucrictibant plasma concentration-time profiles","definition_or_measurement_approach":"Pharmacokinetic profiling of deucrictibant plasma concentration over time."}
• {"endpoint_text":"- Angioedema Quality of Life (AE-QoL) questionnaire","definition_or_measurement_approach":"Patient-reported AE-QoL instrument to assess health-related quality of life."}
• {"endpoint_text":"- Patient Global Assessment of Change (PGA-Change)","definition_or_measurement_approach":"Patient global assessment measure of perceived change."}
• {"endpoint_text":"- Angioedema Control Test 4-week version (AECT-4wk)","definition_or_measurement_approach":"AECT-4wk tool to assess angioedema control over 4 weeks."}
• {"endpoint_text":"- Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP)","definition_or_measurement_approach":"WPAI-SHP instrument assessing work productivity and activity impairment related to HAE."}
• {"endpoint_text":"- Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9)","definition_or_measurement_approach":"TSQM-9 instrument assessing treatment satisfaction."}

Methods

• Country-specific recruitment arrangements and materials were provided (documents present in the CTIS documents list). Channels and materials include: Posters (country-specific K2_Recruitment_Material_Poster documents), Brochures (K2_Recruitment_Material_Brochure), Website recruitment pages (K2_Recruitment_Material_Website), Digital materials (K2_Recruitment_Material_DigitalMaterial / DigitalMaterials), and PI invite letters (K2_Recruitment_Material_PI_Invite_Letter). Materials include country-specific packages (documents available for DE, FR, IT, HU, PL, IE, RO, SK, BG, ES and others).
• Investigator/Principal Investigator invitation letters to referring clinicians (PI Invite Letter documents) to identify potential participants at clinical sites.

Bulgaria

Earliest CTIS Part Ii Submission Date

10-01-2025

Latest Decision Or Authorization Date

10-10-2025

Processing Time Days

273

Number Of Sites

2

Number Of Participants

4

France

Earliest CTIS Part Ii Submission Date

07-01-2025

Latest Decision Or Authorization Date

03-10-2025

Processing Time Days

269

Number Of Sites

6

Number Of Participants

2

Germany

Earliest CTIS Part Ii Submission Date

14-05-2025

Latest Decision Or Authorization Date

08-10-2025

Processing Time Days

147

Number Of Sites

6

Number Of Participants

2

Hungary

Earliest CTIS Part Ii Submission Date

04-12-2024

Latest Decision Or Authorization Date

06-10-2025

Processing Time Days

306

Number Of Sites

1

Number Of Participants

5

Italy

Earliest CTIS Part Ii Submission Date

13-01-2025

Latest Decision Or Authorization Date

06-10-2025

Processing Time Days

266

Number Of Sites

10

Number Of Participants

10

Spain

Earliest CTIS Part Ii Submission Date

09-01-2025

Latest Decision Or Authorization Date

07-10-2025

Processing Time Days

271

Number Of Sites

3

Number Of Participants

6

Poland

Earliest CTIS Part Ii Submission Date

13-01-2025

Latest Decision Or Authorization Date

08-10-2025

Processing Time Days

268

Number Of Sites

1

Number Of Participants

3

Ireland

Earliest CTIS Part Ii Submission Date

12-12-2024

Latest Decision Or Authorization Date

03-10-2025

Processing Time Days

295

Number Of Sites

1

Number Of Participants

1

Romania

Earliest CTIS Part Ii Submission Date

18-10-2024

Latest Decision Or Authorization Date

10-10-2025

Processing Time Days

357

Number Of Sites

1

Number Of Participants

2

Slovakia

Earliest CTIS Part Ii Submission Date

21-01-2025

Latest Decision Or Authorization Date

06-10-2025

Processing Time Days

248

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

Ardena Bioanalysis B.V.

Responsibilities

sponsorDuties codes: [4]

Name

Medpace Reference Laboratories LLC

Responsibilities

sponsorDuties codes: [4]

Name

Hangzhou Tigermed Consulting Co. Ltd.

Responsibilities

sponsorDuties codes: [10]

Name

Eclinical Solutions LLC

Responsibilities

sponsorDuties codes: [6]

Name

Praxis Communications LLC

Responsibilities

Recruitment materials (sponsorDuties code: 15)

Third parties

• {"country":"Netherlands","full_name":"Ardena Bioanalysis B.V.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medpace Reference Laboratories LLC","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"China","full_name":"Hangzhou Tigermed Consulting Co. Ltd.","duties_or_roles":"sponsorDuties codes: [10]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eclinical Solutions LLC","duties_or_roles":"sponsorDuties codes: [6]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Praxis Communications LLC","duties_or_roles":"Recruitment materials","organisation_type":"Non-Pharmaceutical company"}