Study of Oral Deucrictibant XR Tablet for Prophylaxis and Deucrictibant Soft Capsule for On-Demand Treatment of Angioedema Attacks in Adults With Acquired Angioedema Due to C1 Inhibitor Deficiency (CREAATE)
A Phase 3, Randomized, Double-blind, Placebo-controlled, 3-Part Study to Evaluate the Efficacy and Safety of Orally Administered Deucrictibant XR Tablet for Prophylaxis and Deucrictibant Soft Capsule for On-demand Treatment of Angioedema Attacks in Adults With Acquired Angioedema Due to C1 Inhibitor Deficiency
This is a Phase 3, multicenter, 3-part study, with 2 randomized, double-blind, placebo-controlled parts and an open-label extension part, to evaluate the efficacy and safety of orally administered deucrictibant XR tablet for prophylaxis, and deucrictibant soft capsule for on-demand treatment of angioedema attacks in adult participants aged ≥ 18 years with AAE-C1INH.
Přehled studie
Postavení
Intervence / Léčba
Detailní popis
The study consists of a Screening Period, during which eligibility is confirmed, a Part 1 Prophylaxis Double-blind Treatment Phase, a Part 2 On-demand, Double-blind Treatment Phase, and a Part 3 On-demand Open-label Extension Phase. Approximately 24 participants will be randomized in Part 1 into 2 parallel arms for a treatment period of 12 weeks. During the prophylaxis treatment period participants will receive blinded study drug (deucrictibant 40 mg XR or placebo randomized in a 1:1 ratio). Upon completion of Part 1, participants will roll-over into Part 2. In addition to rollover participants completing Part 1, new deucrictibant treatment-naïve participants will be enrolled directly into Part 2 and this may occur while Part 1 is ongoing. During the on-demand period participants will receive blinded study drug (deucrictibant 20 mg soft capsule or matching placebo randomized in a 1:1 ratio, 2-period, 2-treatment crossover design) for 2 qualifying AAE-C1INH attacks. Participants completing Part 2 may roll over into Part 3 where all AAE-C1INH attacks will be treated with open-label deucrictibant 20 mg soft capsule.
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 3
Kontakty a umístění
Studijní kontakt
- Jméno: Pharvaris Clinical Team
- Telefonní číslo: 0031-712-036-410
- E-mail: clinicaltrials@pharvaris.com
Studijní místa
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Clayton, Austrálie
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Sofia, Bulharsko
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Grenoble, Francie
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Lille, Francie
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Paris, Francie
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Amsterdam, Holandsko
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Milan, Itálie
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- Study Site 1
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Milan, Itálie
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- Study Site 2
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Milan, Itálie
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- Study Site 3
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Padova, Itálie
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Roma, Itálie
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Edmonton, Kanada
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Budapest, Maďarsko
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Auckland, Nový Zéland
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Berlin, Německo
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Frankfurt am Main, Německo
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Munich, Německo
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Krakow, Polsko
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Vienna, Rakousko
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Bristol, Spojené království
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Cambridge, Spojené království
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Leicester, Spojené království
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London, Spojené království
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Newcastle upon Tyne, Spojené království
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Plymouth, Spojené království
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California
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San Diego, California, Spojené státy, 92093
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Walnut Creek, California, Spojené státy, 94598,
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Missouri
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St Louis, Missouri, Spojené státy, 63130
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Pennsylvania
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Hershey, Pennsylvania, Spojené státy, 17033
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Ankara, Turecko (Türkiye)
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Madrid, Španělsko
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Basel, Švýcarsko
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Inclusion Criteria:
- Provision of written informed consent
- Male or female (sex at birth) aged ≥18 years
- Diagnosis of AAE-C1INH
- History of AAE-C1INH attacks prior to the Screening Visit.
- If underlying disease associated with AAE is present, the underlying disease must be stable throughout the duration of part 1.
- Reliable access and ability to use available therapy to effectively manage AAE- C1INH attacks.
- 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.
Females of non-childbearing potential (surgically sterile, or postmenopausal with ≥ 12 months amenorrhea and postmenopausal FSH confirmation) are not required to use contraception during the study.
• Capable of recording, without assistance, eDiary and ePRO data using an electronic device, as evidenced by the eDiary and ePRO training.
Exclusion Criteria:
- 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).
- Receiving long-term prophylaxis (LTP) treatment for AAE-C1INH and satisfied with this treatment. Participants who are not satisfied (eg, tolerability issues, lack of efficacy) and have previously stopped LTP treatment for AAE-C1INH, for reasons other than participation in this study, can sign the ICF and begin the Screening Period only if their last dose of the treatment was received prior to the timepoint before the Screening Visit
- Any females who are pregnant, plan to become pregnant, or are currently breast-feeding
- Abnormal hepatic function
- Moderate or severe renal impairment
- Any clinically significant comorbidity or systemic dysfunction that would interfere with the participant's safety or ability to participate in the study.
- History of epilepsy and/or other significant neurological diseases
- Any clinically significant and uncontrolled gastrointestinal dysfunction that may impact study drug absorption
- Evidence of current alcohol or drug abuse
- Use of medications that are moderate and strong inhibitors of cytochrome P450 (CYP) 3A4, or strong inducers of CYP3A4 within the last 30 days or within 5 half-lives (whichever is longer) at the time of the Screening Visit
- Known hypersensitivity to deucrictibant or any of the excipients of the study drug
- Use of angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption within 5 half-lives before the Screening Visit
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Čtyřnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: Část 1 - Rameno 1 - Aktivní
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Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use Part 2: Deucrictibant 20 mg soft capsule oral use Part 3: Deucrictibant 20 mg soft capsule oral use |
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Komparátor placeba: Část 1 - Skupina 2 - Placebo
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Part 1: Placebo Comparator tablet for once daily oral use Part 2: Placebo Comparator soft capsule oral use |
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Experimentální: Část 2 - Skupina 1
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Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use Part 2: Deucrictibant 20 mg soft capsule oral use Part 3: Deucrictibant 20 mg soft capsule oral use Part 1: Placebo Comparator tablet for once daily oral use Part 2: Placebo Comparator soft capsule oral use |
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Experimentální: Část 2 - Rameno 2
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Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use Part 2: Deucrictibant 20 mg soft capsule oral use Part 3: Deucrictibant 20 mg soft capsule oral use Part 1: Placebo Comparator tablet for once daily oral use Part 2: Placebo Comparator soft capsule oral use |
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Experimentální: Část 3 - Open-label
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Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use Part 2: Deucrictibant 20 mg soft capsule oral use Part 3: Deucrictibant 20 mg soft capsule oral use |
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Časové okno |
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Part 1: Time-normalized number of Investigator-confirmed AAE-C1INH attacks during Treatment Phase
Časové okno: 12 weeks
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12 weeks
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Part 2: Time to symptom relief, Patient Global Impression of Change (PGI-C) rating of at least "better"
Časové okno: 12 hours post-treatment
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12 hours post-treatment
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Part 3: Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent adverse events of special interest (AESIs), and serious adverse events (SAEs)
Časové okno: Through study termination, an average of 36 weeks
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Through study termination, an average of 36 weeks
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Part 3: Number of participants with clinically significant changes from baseline in Hematology parameters
Časové okno: Through study termination, an average of 36 weeks
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Through study termination, an average of 36 weeks
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Part 3: Number of participants with clinically significant changes from baseline in Urinalysis parameters
Časové okno: Through study termination, an average of 36 weeks
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Through study termination, an average of 36 weeks
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Part 3: Number of participants with clinically significant changes from baseline in Biochemistry parameters
Časové okno: Through study termination, an average of 36 weeks
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Through study termination, an average of 36 weeks
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Part 3: Number of participants with clinically significant changes from baseline in vital signs
Časové okno: Through study termination, an average of 36 weeks
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Through study termination, an average of 36 weeks
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Part 3: Number of participants with clinically significant changes from baseline in physical examinations
Časové okno: Through study termination, an average of 36 weeks
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Through study termination, an average of 36 weeks
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Part 3: Number of participants with clinically significant changes in electrocardiogram (ECG)
Časové okno: Through study termination, an average of 36 weeks
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Through study termination, an average of 36 weeks
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Part 1: Proportion of participants who are AAE-C1INH attack-free during Treatment Phase
Časové okno: 12 weeks
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12 weeks
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Part 1: Time-normalized number of Investigator-confirmed AAE-C1INH attacks treated with on-demand medication during Treatment Phase
Časové okno: 12 weeks
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12 weeks
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Part 1: Time-normalized number of Investigator-confirmed moderate or severe AAE-C1INH attacks during Treatment Phase
Časové okno: 12 weeks
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12 weeks
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Part 1: Time-normalized number of Investigator-confirmed severe AAE-C1INH attacks during Treatment Phase
Časové okno: 12 weeks
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12 weeks
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Part 1: Proportion of participants achieving ≥50%, ≥70% and ≥90% reduction in AAE-C1NH attack rate relative to baseline during Treatment Phase
Časové okno: 12 weeks
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12 weeks
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Part 1: Incidence of TEAEs, treatment-emergent AESIs, and SAEs
Časové okno: 12 weeks
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12 weeks
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Part 1: Number of participants with clinically significant changes from baseline in Hematology parameters
Časové okno: 12 weeks
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12 weeks
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Part 1: Number of participants with clinically significant changes from baseline in Urinalysis parameters
Časové okno: 12 weeks
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12 weeks
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Part 1: Number of participants with clinically significant changes from baseline in Biochemistry parameters
Časové okno: 12 weeks
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12 weeks
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Part 1: Number of participants with clinically significant changes from baseline in Vital signs
Časové okno: 12 weeks
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12 weeks
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Part 1: Number of participants with clinically significant changes from baseline in physical examination
Časové okno: 12 weeks
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12 weeks
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Part 1: Number of participants with clinically significant changes from baseline in ECG parameters
Časové okno: 12 weeks
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12 weeks
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Part 1: Pre-dose plasma concentrations of Deucrictibant
Časové okno: At Weeks 6 and 12
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Deucrictibant plasma concentrations will be analyzed using liquid chromatography-mass spectrometry/mass spectrometry methods |
At Weeks 6 and 12
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Part 1: Pre-dose plasma concentrations of deucrictibant metabolites
Časové okno: At Weeks 6 and 12
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Deucrictibant metabolites plasma concentrations will be analyzed using liquid chromatography-mass spectrometry/mass spectrometry methods |
At Weeks 6 and 12
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Part 1: Pharmacokinetics [PK]: Urine concentrations of Deucrictibant and deucrictibant metabolites
Časové okno: At Week 12
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At Week 12
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Part 1: Change from baseline in Angioedema Quality of Life (AE-QoL) questionnaire total score, functioning domain score, and fears/shame domain score
Časové okno: Baseline (Day 1) and at Weeks 4, 8 and 12
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The AE-QoL is a short 17-item questionnaire designed to retrospectively assess HRQoL, with a recall period of 4 weeks. Its results can be displayed as a total score or as 4 domain scores. The scores range from 0 to 100, after linear transformation of raw values, with higher scores indicating higher HRQoL impairment. |
Baseline (Day 1) and at Weeks 4, 8 and 12
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Part 1: Change from baseline in Angioedema Control Test 4-week version (AECT-4wk)
Časové okno: Baseline (Day 1) and at Week 12
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AECT-4wk measures disease control retrospectively, it comprises 4 questions over a 4-week recall period. Scores for the responses in the AECT range from 0 to 16, with higher scores indicating better disease control (≤ 9 poorly controlled; ≥ 10 well controlled) |
Baseline (Day 1) and at Week 12
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Part 1: Patient Global Assessment-Status (PGA-S) at baseline
Časové okno: At Baseline (Day 1)
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PGA-Status assesses on a 5-point scale how the participant's QoL has been impacted by AAE-C1INH since start taking the study drug |
At Baseline (Day 1)
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Part 1: Patient Global Assessment of Change (PGA-Change) at Week 12
Časové okno: At Week 12
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PGA-Change assesses on a 5-point scale how the participant's QoL has been impacted by AAE-C1INH since start taking the study drug |
At Week 12
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Part 1: Change from baseline in EuroQol 5 Dimension 5 level (EQ 5D 5L)
Časové okno: Baseline (Day 1) and at Week 12
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EQ 5D 5L is a brief, multiattribute, generic, health status measure composed of 5 questions with Likert response options (descriptive system) and a visual analog scale (EQ-VAS). The latter asks patients to rate their own health from 0 to 100 (the worst and best imaginable health, respectively) |
Baseline (Day 1) and at Week 12
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Part 2: Time to complete symptom resolution, Patient Global Impression of Severity (PGI-S) rating of "no symptoms
Časové okno: sustained within 24 hours post-treatment
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sustained within 24 hours post-treatment
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Part 2: Time to symptom relief defined as PGI-S rating of at least 1 point reduction
Časové okno: 12 hours post-treatment
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12 hours post-treatment
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Part 2: Proportion of study drug-treated attacks achieving complete symptom resolution defined as achieving PGI- S rating of "no symptoms"
Časové okno: At 24 hours post-treatment
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At 24 hours post-treatment
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Part 2: Time to onset of symptom relief, defined as PGI-C rating of at least "a little better"
Časové okno: Within 12 hours post-treatment
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Within 12 hours post-treatment
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Part 2: Time to End of Progression (EoP) in attack symptoms
Časové okno: Within 12 hours post-treatment
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EOP is defined as the earliest post-treatment timepoint after which all subsequent PGI-C ratings are stable or improved |
Within 12 hours post-treatment
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Part 2: Incidence of TEAEs, treatment-emergent AESIs, and SAEs
Časové okno: Up to 24 weeks
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Up to 24 weeks
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Part 2: Number of participants with clinically significant changes from baseline in Hematology parameters
Časové okno: 24 weeks
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24 weeks
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Part 2: Number of participants with clinically significant changes from baseline in Urinalysis parameters
Časové okno: 24 weeks
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24 weeks
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Part 2: Number of participants with clinically significant changes from baseline in Biochemistry parameters
Časové okno: 24 weeks
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24 weeks
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Part 2: Number of participants with clinically significant changes from baseline in Vital signs
Časové okno: 24 weeks
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24 weeks
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Part 2: Number of participants with clinically significant changes from baseline in physical examination
Časové okno: 24 weeks
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24 weeks
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Part 2: Number of participants with clinically significant changes from baseline in ECG parameters
Časové okno: 24 weeks
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24 weeks
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Part 2: Pharmacokinetics [PK]: Deucrictibant and deucrictibant metabolites plasma concentration-time profiles
Časové okno: Day 1
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Day 1
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Part 3: Time to symptom relief, as PGI-C rating of at least "better"
Časové okno: 12 hours post-treatment
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12 hours post-treatment
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Part 3: Time to symptom relief, as PGI-S rating of at least 1 point reduction
Časové okno: 12 hours post-treatment
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12 hours post-treatment
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Part 3: Proportion of study drug-treated attacks achieving complete symptom resolution, defined as achieving PGI-S rating of "no symptoms"
Časové okno: 24 hours post-treatment
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24 hours post-treatment
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Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Ředitel studie: Study Director, Pharvaris, Pharvaris Netherlands B.V.
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Dědičná onemocnění z nedostatku komplementu
- Primární imunodeficitní onemocnění
- Cévní onemocnění
- Kardiovaskulární choroby
- Genetické choroby, vrozené
- Onemocnění imunitního systému
- Přecitlivělost, okamžitá
- Přecitlivělost
- Syndromy imunologické nedostatečnosti
- Kožní choroby
- Kopřivka
- Kožní onemocnění, Cévní
- Vrozené, dědičné a neonatální nemoci a abnormality
- Onemocnění kůže a pojivové tkáně
- Angioedém
- Angioedémy, dědičné
- Získaný angioedém
Další identifikační čísla studie
- PHA022121-C308
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