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 angioedem
Conditions
Sponsors
Pharvaris Netherlands BV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of written informed consent. 2. Male or female, aged = 18 years at the time of providing written informed consent. 3. Patients must have received at least 1 dose of study drug (including the non-attack visit) in Study PHA022121-C201. 4. Female patients of childbearing potential must agree to the protocol specified pregnancy testing and to be abstinent from heterosexual intercourse or to use an acceptable form of contraception methods from enrollment until 30 days after the last study drug administration. Methods acceptable for this study include male condom with or without spermicide, cervical cap, diaphragm or sponge with spermicide, a combination of male condom with cap, diaphragm or sponge with spermicide (double-barrier methods), progestin-only hormonal methods (oral, injectable, or implantable), intrauterine device (IUD, all types), intrauterine hormone releasing systems (IUS). Females of non-childbearing potential, defined as surgically sterile (status post hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or post-menopausal (defined as no menses for at least 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) test result indicative of post-menopausal status) do not require contraception during the study. There are no contraceptive requirements for male patients. 5. In the opinion of the investigator is willing and able to comply with the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 54 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: 1. Any female who is pregnant or is breast-feeding. 2. Presence of any medical condition that could interfere with the assessment of safety or efficacy or negatively affect the patient’s safety, including clinically significant abnormal ECG, most notably a QTcF > 470 ms (for females) or > 450 ms (for males), cardiovascular disease, abnormal liver function and abnormal kidney function. 3. Any other systemic disease (e.g., gastrointestinal, renal, respiratory, neurological) or significant disease or disorder that would interfere with the patient’s safety or ability to participate in the study. 4. Use of lanadelumab for long-term HAE prophylactic therapy within 12 weeks prior to study enrollment. Patients who have recently used short or long-term HAE prophylaxis or on-demand HAE treatment will not be excluded from the study provided the following washout period is observed (i.e., study screening or enrollment should be delayed allowing for washout): • 2-week washout period before enrollment should be respected for patients who have used any C1-INH product, oral kallikrein inhibitors, attenuated androgens, or anti-fibrinolytics for long-term prophylactic HAE therapy. • 1-week washout period before enrollment should be respected for patients who have used plasma derived C1-INH concentrates (Berinert, Cinryze, Haegarda) for on-demand treatment or short-term prophylaxis. • 24-hour washout period before enrollment should be respected for patients who have used recombinant C1-INH (Ruconest) for on-demand treatment or short-term prophylaxis. 6. History of alcohol or drug abuse within the previous year, or current evidence of substance dependence or abuse. 7. Discontinued from Study PHA022121-C201 after enrollment for any study drug-related safety reason. 8. Participation in any other investigational drug study (except with PHA-022121) currently, within the last 30 days prior to the first PHA-022121 dose or within 5 half-lives of study drug at enrollment, whichever is longer. 9. Use of concomitant medications that are potent CYP3A4 inhibitors (e.g., clarithromycin, erythromycin, itraconazole, ketoconazole, ritonavir, grapefruit) or potent CYP3A4 inducers (e.g., phenytoin, rifampicin, St. John's Wort).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety of long-term on-demand treatment with PHA-022121 for acute hereditary angioedema (HAE) attacks including laryngeal attacks.;Secondary Objective: • To evaluate the efficacy of PHA-022121 in achieving symptom relief in patients with acute HAE attacks including laryngeal attacks, • To evaluate the maintenance of PHA-022121 efficacy in achieving symptom relief for any subsequent acute HAE attacks including laryngeal attacks, • To evaluate the proportion of PHA-022121-treated attacks requiring a second dose of PHA-022121 to achieve symptom relief.;Primary end point(s): The primary endpoints of the study are •TEAEs, treatment-related TEAEs, treatment-emergent serious adverse events (TESAEs), and treatment-related TESAEs • Clinical laboratory tests • Vital signs;Timepoint(s) of evaluation of this end point: • TEAES will be evaluated when taking place • Clinical laboratory tests will be evaluated as follows: Part A: at Screening visit and every 3 months Part B: when patients transition to Part B, then every 3 months for the first 6 months, and every 6 months thereafter and 14 to 28 days after the last treatment administration • Vital signs Part A: at Screening visit and every 3 months Part B: when patients transition to Part B, then every 3 months for the first 6 months, and every 6 months thereafte | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Time to onset of symptom relief (TOSR) defined as = 50% reduction in VAS-3 or VAS-5 • Time to almost complete (defined as all individual VAS scores are =10) or complete (defined as all individual VAS scores = 0) symptom relief (TACSR and TCSR) assessed by VAS-3 or VAS-5 • Time to symptom improvement based on PGI-S • Time to symptom improvement based on PGI-C • Change of VAS-3 score and individual VAS score from pre-treatment to 4 h post-treatment for non-laryngeal attacks • Change in MSCS score at 4 h post-treatment • TOS at 4 h post-treatment • Proportion of PHA-022121-treated attacks requiring a second dose of PHA-022121 • TSQM scores at 48 h post-treatment;Timepoint(s) of evaluation of this end point: -VAS-3 *; VAS-5**, PGI-S and PGI-C: every hour (±30 min) up to 6 h from initiation of PHA-022121 treatment and then at 8 (±1.5 h), 12 h (±2.5 h), 24 h (±9.5 h), and 48 h (±14.5 h) from initiation of treatment -MSCS-TOS: at 4 h (±30 min), 12 h (±2.5 h), 24 h (±9.5 h), and 48 h (±14.5 h) from initiation of the PHA-022121 treatment -TSQM score: at 48 h (±14.5 h) from initiation of the PHA-022121 treatment * Non-laryngeal Attacks only ** Laryngeal attacks only | — |
Countries
Bulgaria, Canada, Czechia, France, Germany, Hungary, Israel, Italy, Poland, Spain, United Kingdom, United States
Contacts
Public ContactPharvaris Clinical
Pharvaris Netherlands BV
Outcome results
None listed