Studio di dose-ranging di PHA-022121 orale per la profilassi contro gli attacchi di angioedema in pazienti con angioedema ereditario di tipo I o di tipo II (HAE CHAPTER-1)
12 agosto 2026 aggiornato da: Pharvaris Netherlands B.V.
Uno studio di fase II, in doppio cieco, controllato con placebo, randomizzato, a dosaggio variabile, a gruppi paralleli per valutare la sicurezza e l'efficacia di PHA-022121 somministrato per via orale per la profilassi contro gli attacchi di angioedema in pazienti con angioedema ereditario dovuto a carenza di C1-inibitore ( Tipo I o Tipo II)
Questo studio valuta la sicurezza e l'efficacia di PHA-022121 somministrato per via orale per la profilassi contro gli attacchi di angioedema in pazienti con angioedema ereditario (HAE).
Lo studio è composto da 2 parti, con i pazienti che completano la partecipazione alla Parte 1 prima dell'inizio del trattamento nella Parte 2. La Parte 1 dello studio ha 3 bracci paralleli e circa 30 pazienti saranno ugualmente randomizzati a uno dei due regimi posologici di PHA-022121 o placebo corrispondente.
I pazienti continueranno al braccio singolo in aperto nella Parte 2 dello studio dopo il completamento della Parte 1.
Il periodo di screening è fino a 8 settimane e i periodi di trattamento hanno una durata di 12 settimane (Parte 1) e 50 settimane (Parte 2).
Panoramica dello studio
Stato
Terminato
Condizioni
- Angioedema ereditario
- Angioedema ereditario di tipo I
- Angioedema ereditario di tipo II
- Angioedema ereditario di tipo I e II
- Attacco di angioedema ereditario
- Angioedema ereditario con carenza di inibitore dell'esterasi C1
- Angioedema ereditario - Tipo 1
- Angioedema ereditario - Tipo 2
- Carenza di inibitore dell'esterasi C1
- Carenza di inibitore C1
Intervento / Trattamento
Tipo di studio
Interventistico
Iscrizione (Effettivo)
34
Fase
- Fase 2
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
-
-
-
Vienna, Austria, A-1090
- Study Site
-
-
-
-
-
Sofia, Bulgaria, 1680
- Study Site
-
-
-
-
Ontario
-
Ottawa, Ontario, Canada, K1H 1E4
- Study Site
-
-
Quebec
-
Montreal, Quebec, Canada, H2W 1R7
- Study Site
-
-
-
-
-
Berlin, Germania, 10117
- Study Site
-
Frankfurt, Germania, 60323
- Study Site
-
-
-
-
-
Dublin, Irlanda, D08NHY1
- Study Site
-
-
-
-
-
Milan, Italia, 20157
- Study Site
-
Palermo, Italia, 0146
- Study Site
-
-
PD
-
Padua, PD, Italia, 35128
- Study Site
-
-
-
-
-
Krakow, Polonia
- Study Site
-
-
-
-
England
-
Brighton, England, Regno Unito, BN2 1ES
- Study Site
-
Bristol, England, Regno Unito, BS10 5NB
- Study Site
-
Cambridge, England, Regno Unito, CB2 0QQ
- Study Site
-
London, England, Regno Unito, E1 1FR
- Study Site
-
Southampton, England, Regno Unito, SO16 6YD
- Study Site
-
-
-
-
Alabama
-
Birmingham, Alabama, Stati Uniti, 35209
- Study Site
-
-
Arizona
-
Paradise Valley, Arizona, Stati Uniti, 85253
- Study Site
-
-
Missouri
-
St Louis, Missouri, Stati Uniti, 63141
- Study Site
-
-
Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
Da 18 anni a 75 anni (Adulto, Adulto più anziano)
Accetta volontari sani
No
Descrizione
Criterio di inclusione:
- Modulo di consenso informato firmato e datato
- Diagnosi di HAE di tipo I o II
- Storia documentata di almeno 3 attacchi di HAE negli ultimi 3 mesi consecutivi prima dello screening, o un minimo di 2 attacchi di HAE durante il periodo di screening
- Accesso affidabile ed esperienza nell'uso di farmaci standard per attacchi acuti
Criteri di esclusione:
- Gravidanza o allattamento
- Elettrocardiogramma anomalo clinicamente significativo
- Qualsiasi altra malattia sistemica o malattia o disturbo significativo che possa interferire con la sicurezza o la capacità del paziente di partecipare allo studio
- Uso di inibitore della C1-esterasi, inibitori orali della callicreina, androgeni attenuati, antifibrinolitici o terapia HAE monoclonale entro un periodo definito prima dell'arruolamento
- Funzionalità epatica anomala
- Funzionalità renale anormale
- Storia di abuso di alcol o droghe entro un periodo definito o prove attuali di dipendenza o abuso di sostanze
- Partecipazione a qualsiasi altro studio sperimentale sui farmaci entro un periodo definito
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Prevenzione
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Quadruplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Comparatore placebo: Parte 1: Placebo
BID placebo
|
Capsule placebo corrispondenti per uso orale
|
|
Sperimentale: Parte 1: Dose bassa
BID bassa dose di deucrictibant
|
Capsule softgel deucrictibant per uso orale (PHVS416)
|
|
Sperimentale: Parte 1: dose elevata
BID dose elevata di deucrictibant
|
Capsule softgel deucrictibant per uso orale (PHVS416)
|
|
Sperimentale: Parte 2: in aperto
BID dose elevata di deucrictibant
|
Capsule softgel deucrictibant per uso orale (PHVS416)
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Number of Investigator-confirmed Hereditary Angioedema (HAE) Attacks (Expressed as the Normalized Number of Attacks Per Month [4 Weeks] of Exposure) During the Treatment Period in Part 1
Lasso di tempo: Up to Day 84
|
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx).
A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack.
Attacks were recorded via daily electronic patient-reported outcome (ePRO) diaries and confirmed by the investigator.
Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28.
Mean rate ratio, confidence interval (CI), and p-value were estimated using a generalized linear model with Poisson distribution, with baseline attack rate included as a factor.
|
Up to Day 84
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Number of Investigator-confirmed Moderate or Severe HAE Attacks During the Treatment Period in Part 1
Lasso di tempo: Up to Day 84
|
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx).
A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack.
Attacks were recorded via daily ePRO diaries and confirmed by the investigator.
Monthly attack rate was calculated as number of attacks during treatment divided by treatment days×28.
Moderate HAE attack defined as which limits/interferes with the participant's ability to attend work/school or participate in family life and social/recreational activities whereas Severe HAE attack significantly limits the participant's ability.
|
Up to Day 84
|
|
Number of Investigator-confirmed HAE Attacks Requiring Acute Treatment During the Treatment Period in Part 1
Lasso di tempo: Up to Day 84
|
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx).
A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack.
Attacks were recorded via daily ePRO diaries and confirmed by the investigator.
Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28.
|
Up to Day 84
|
|
Number of Participants Achieving ≥50%, ≥70% and ≥90% Reduction in Attack Rate Relative to Baseline During the Treatment Period in Part 1
Lasso di tempo: Up to Day 84
|
Baseline attack rate was defined as each participant's normalized HAE attack rate (attacks per 4 weeks) prior to randomization, based on documented history or confirmed during screening.
Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28.
Percent reduction from baseline was calculated for each participant by comparing the normalized treatment-period attack rate to the baseline attack rate.
Participants were classified as responders if they achieved ≥50%, ≥70%, or ≥90% reduction in attack rate relative to baseline during Part 1.
|
Up to Day 84
|
|
Number of Participants Who Were Investigator-confirmed Attack-free During the Treatment Period in Part 1
Lasso di tempo: Up to Day 84
|
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx).
A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack.
Attacks were recorded via daily ePRO diaries and confirmed by the investigator.
Participants reporting no confirmed attacks over the treatment period were considered attack-free.
|
Up to Day 84
|
|
Number of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 1
Lasso di tempo: Up to Day 84
|
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx).
HAE symptom days were identified from daily participant entries in the ePRO diary and were confirmed by the investigator.
|
Up to Day 84
|
|
Proportion of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 1
Lasso di tempo: Up to Day 84
|
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx).
HAE symptom days were identified from daily participant entries in the ePRO diary and were confirmed by the investigator.
|
Up to Day 84
|
|
Time to First Investigator-confirmed HAE Attack in the Treatment Period in Part 1
Lasso di tempo: Up to Day 84
|
Time to first investigator-confirmed HAE attack was defined as days from date of first administration of study drug until the onset date of first Investigator-confirmed HAE attack.
Participants without an Investigator-confirmed HAE attack during the treatment period in Part 1 were censored at the date of the last dose of study drug +1 in Part 1 or last day of the study, whichever came sooner.
|
Up to Day 84
|
|
Number of Investigator-confirmed HAE Attacks Resulting in a Visit to the Emergency Department or an Admission to Hospital During the Treatment Period in Part 1
Lasso di tempo: Up to Day 84
|
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx).
A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack.
Attacks were recorded via daily ePRO diaries and confirmed by the investigator.
Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28.
Only Investigator-confirmed attacks resulting in emergency department visits or hospital admissions were included.
|
Up to Day 84
|
|
Number of Investigator-confirmed HAE Attacks During the Treatment Period in Part 2
Lasso di tempo: Day 84 to Day 938
|
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx).
A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack.
Attacks were recorded via daily ePRO diaries and confirmed by the investigator.
Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28.
An attack will be counted as in Part 2 if it occurs after the first IMP administration in Part 2 and within 24 hours after last IMP administration in Part 2.
|
Day 84 to Day 938
|
|
Number of Investigator-confirmed Moderate or Severe HAE Attacks During the Treatment Period in Part 2
Lasso di tempo: Day 84 to Day 938
|
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx).
Attacks were recorded via daily ePRO diaries and confirmed by the investigator.
Monthly attack rate was calculated as number of attacks during treatment divided by treatment days×28.
Moderate HAE attack defined as which limits/interferes with the participant's ability to attend work/school or participate in family life and social/recreational activities whereas Severe HAE attack significantly limits the participant's ability.
LSM and SE were estimated using a generalized linear model with Poisson distribution.
|
Day 84 to Day 938
|
|
Number of Investigator-confirmed HAE Attacks Requiring Acute Treatment During the Treatment Period in Part 2
Lasso di tempo: Day 84 to Day 938
|
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx).
A new attack was counted if symptoms occurred ≥24 hours after complete resolution of a prior attack.
Attacks were recorded via daily ePRO diaries and confirmed by the investigator.
Monthly attack rate was calculated as number of attacks during treatment divided by treatment days, multiplied by 28.
LSM and SE were estimated using a generalized linear model with Poisson distribution.
|
Day 84 to Day 938
|
|
Number of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 2
Lasso di tempo: Day 84 to Day 938
|
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx).
HAE symptom days were identified from daily participant entries in the ePRO diary and were confirmed by the investigator.
|
Day 84 to Day 938
|
|
Proportion of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 2
Lasso di tempo: Day 84 to Day 938
|
HAE attack was defined as signs or symptoms in ≥1 location: peripheral angioedema (cutaneous swelling involving an extremity, face, neck, torso, and/or genitourinary region), abdominal angioedema (abdominal pain with or without abdominal distension, nausea, vomiting, or diarrhea), or upper airway angioedema (lump sensation, difficulty swallowing, throat tightening, difficulty speaking, hoarseness, stridor, dyspnea, or swelling of tongue, palate, uvula, or larynx).
HAE symptom days were identified from daily participant entries in the ePRO diary and were confirmed by the investigator.
|
Day 84 to Day 938
|
Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Investigatori
- Investigatore principale: Marc Riedl, MD, UC San Diego, La Jolla, California, United States
- Investigatore principale: Emel Aygören-Pürsün, MD, University Hospital Frankfurt - Goethe University, Frankfurt, Germany
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio (Effettivo)
19 aprile 2022
Completamento primario (Effettivo)
30 giugno 2025
Completamento dello studio (Effettivo)
30 giugno 2025
Date di iscrizione allo studio
Primo inviato
7 settembre 2021
Primo inviato che soddisfa i criteri di controllo qualità
7 settembre 2021
Primo Inserito (Effettivo)
17 settembre 2021
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
17 agosto 2026
Ultimo aggiornamento inviato che soddisfa i criteri QC
12 agosto 2026
Ultimo verificato
1 agosto 2026
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Malattie ereditarie da carenza di complemento
- Malattie da immunodeficienza primaria
- Malattie vascolari
- Malattia cardiovascolare
- Malattie genetiche, congenite
- Malattie del sistema immunitario
- Ipersensibilità, immediata
- Ipersensibilità
- Sindromi da deficit immunologico
- Malattie della pelle
- Orticaria
- Malattie della pelle, vascolari
- Malattie e anomalie congenite, ereditarie e neonatali
- Malattie della pelle e del tessuto connettivo
- Angioedema
- Angioedema, ereditario
- Angioedema ereditario di tipo I e II
Altri numeri di identificazione dello studio
- PHA022121-C301
- 2021-000227-13 (Numero EudraCT)
Piano per i dati dei singoli partecipanti (IPD)
Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?
NO
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
Sì
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
No
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .