Étude de dosage de PHA-022121 par voie orale pour la prophylaxie contre les crises d'angio-œdème chez les patients atteints d'angio-œdème héréditaire de type I ou de type II (HAE CHAPTER-1)
12 août 2026 mis à jour par: Pharvaris Netherlands B.V.
Une étude de phase II, à double insu, contrôlée par placebo, randomisée, à dose variable, en groupes parallèles pour évaluer l'innocuité et l'efficacité du PHA-022121 administré par voie orale pour la prophylaxie contre les crises d'angio-œdème chez les patients atteints d'angio-œdème héréditaire dû à un déficit en inhibiteur C1 ( type I ou type II)
Cette étude évalue l'innocuité et l'efficacité du PHA-022121 administré par voie orale pour la prophylaxie contre les crises d'angio-œdème chez les patients atteints d'angio-œdème héréditaire (AOH).
L'étude se compose de 2 parties, les patients complétant la participation à la partie 1 avant le début du traitement dans la partie 2. La partie 1 de l'étude comporte 3 bras parallèles et environ 30 patients seront également randomisés pour recevoir l'un des deux schémas posologiques de PHA-022121. ou un placebo correspondant.
Les patients continueront dans le bras unique en ouvert de la partie 2 de l'étude après la fin de la partie 1.
La période de dépistage dure jusqu'à 8 semaines et les périodes de traitement sont de 12 semaines (Partie 1) et 50 semaines (Partie 2).
Aperçu de l'étude
Statut
Résilié
Les conditions
- Angiœdème héréditaire
- Angiœdème héréditaire de type I
- Angiœdème héréditaire de type II
- Angiœdème héréditaire de types I et II
- Attaque d'angio-œdème héréditaire
- Angiœdème héréditaire avec déficit en inhibiteur de la C1 estérase
- Angiœdème héréditaire - Type 1
- Angiœdème héréditaire - Type 2
- Déficit en inhibiteur de la C1 estérase
- Déficit en inhibiteur C1
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
34
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Berlin, Allemagne, 10117
- Study Site
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Frankfurt, Allemagne, 60323
- Study Site
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Sofia, Bulgarie, 1680
- Study Site
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Ontario
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Ottawa, Ontario, Canada, K1H 1E4
- Study Site
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Quebec
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Montreal, Quebec, Canada, H2W 1R7
- Study Site
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Dublin, Irlande, D08NHY1
- Study Site
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Milan, Italie, 20157
- Study Site
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Palermo, Italie, 0146
- Study Site
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PD
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Padua, PD, Italie, 35128
- Study Site
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Vienna, L'Autriche, A-1090
- Study Site
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Krakow, Pologne
- Study Site
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England
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Brighton, England, Royaume-Uni, BN2 1ES
- Study Site
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Bristol, England, Royaume-Uni, BS10 5NB
- Study Site
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Cambridge, England, Royaume-Uni, CB2 0QQ
- Study Site
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London, England, Royaume-Uni, E1 1FR
- Study Site
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Southampton, England, Royaume-Uni, SO16 6YD
- Study Site
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Alabama
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Birmingham, Alabama, États-Unis, 35209
- Study Site
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Arizona
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Paradise Valley, Arizona, États-Unis, 85253
- Study Site
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Missouri
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St Louis, Missouri, États-Unis, 63141
- Study Site
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans à 75 ans (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
La description
Critère d'intégration:
- Formulaire de consentement éclairé signé et daté
- Diagnostic d'AOH de type I ou II
- Antécédents documentés d'au moins 3 crises d'AOH au cours des 3 derniers mois consécutifs avant le dépistage, ou d'un minimum de 2 crises d'AOH pendant la période de dépistage
- Accès fiable et expérience pour utiliser les médicaments d'attaque aiguë standard de soins
Critère d'exclusion:
- Grossesse ou allaitement
- Électrocardiogramme anormal cliniquement significatif
- Toute autre maladie systémique ou maladie ou trouble important qui interférerait avec la sécurité du patient ou sa capacité à participer à l'étude
- Utilisation d'un inhibiteur de la C1-estérase, d'inhibiteurs de la kallikréine par voie orale, d'androgènes atténués, d'anti-fibrinolytiques ou d'un traitement monoclonal de l'AOH pendant une période définie avant l'inscription
- Fonction hépatique anormale
- Fonction rénale anormale
- Antécédents d'abus d'alcool ou de drogues au cours d'une période définie, ou preuves actuelles de dépendance ou d'abus de substances
- Participation à toute autre étude de médicament expérimental dans un délai défini
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: La prévention
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Comparateur placebo: Partie 1 : Placebo
BID placebo
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Capsules placebo assorties à usage oral
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Expérimental: Partie 1 : Faible dose
BID faible dose de déucrictibant
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Capsules molles de deucrictibant à usage oral (PHVS416)
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Expérimental: Partie 1 : Haute dose
BID dose élevée de déucrictibant
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Capsules molles de deucrictibant à usage oral (PHVS416)
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Expérimental: Partie 2 : Open-label
BID dose élevée de déucrictibant
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Capsules molles de deucrictibant à usage oral (PHVS416)
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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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
Délai: Up to Day 84
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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.
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Up to Day 84
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Number of Investigator-confirmed Moderate or Severe HAE Attacks During the Treatment Period in Part 1
Délai: Up to Day 84
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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.
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Up to Day 84
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Number of Investigator-confirmed HAE Attacks Requiring Acute Treatment During the Treatment Period in Part 1
Délai: Up to Day 84
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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.
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Up to Day 84
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Number of Participants Achieving ≥50%, ≥70% and ≥90% Reduction in Attack Rate Relative to Baseline During the Treatment Period in Part 1
Délai: Up to Day 84
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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.
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Up to Day 84
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Number of Participants Who Were Investigator-confirmed Attack-free During the Treatment Period in Part 1
Délai: Up to Day 84
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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.
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Up to Day 84
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Number of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 1
Délai: Up to Day 84
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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.
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Up to Day 84
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Proportion of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 1
Délai: Up to Day 84
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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.
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Up to Day 84
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Time to First Investigator-confirmed HAE Attack in the Treatment Period in Part 1
Délai: Up to Day 84
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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.
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Up to Day 84
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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
Délai: Up to Day 84
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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.
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Up to Day 84
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Number of Investigator-confirmed HAE Attacks During the Treatment Period in Part 2
Délai: Day 84 to Day 938
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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.
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Day 84 to Day 938
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Number of Investigator-confirmed Moderate or Severe HAE Attacks During the Treatment Period in Part 2
Délai: Day 84 to Day 938
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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.
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Day 84 to Day 938
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Number of Investigator-confirmed HAE Attacks Requiring Acute Treatment During the Treatment Period in Part 2
Délai: Day 84 to Day 938
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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.
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Day 84 to Day 938
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Number of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 2
Délai: Day 84 to Day 938
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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.
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Day 84 to Day 938
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Proportion of Days With Investigator-confirmed HAE Symptoms During the Treatment Period in Part 2
Délai: Day 84 to Day 938
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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.
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Day 84 to Day 938
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Chercheur principal: Marc Riedl, MD, UC San Diego, La Jolla, California, United States
- Chercheur principal: Emel Aygören-Pürsün, MD, University Hospital Frankfurt - Goethe University, Frankfurt, Germany
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
19 avril 2022
Achèvement primaire (Réel)
30 juin 2025
Achèvement de l'étude (Réel)
30 juin 2025
Dates d'inscription aux études
Première soumission
7 septembre 2021
Première soumission répondant aux critères de contrôle qualité
7 septembre 2021
Première publication (Réel)
17 septembre 2021
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
17 août 2026
Dernière mise à jour soumise répondant aux critères de contrôle qualité
12 août 2026
Dernière vérification
1 août 2026
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies héréditaires de déficience du complément
- Maladies d'immunodéficience primaire
- Maladies vasculaires
- Maladies cardiovasculaires
- Maladies génétiques, innées
- Maladies du système immunitaire
- Hypersensibilité immédiate
- Hypersensibilité
- Syndromes d'immunodéficience
- Maladies de la peau
- Urticaire
- Maladies de la peau, vasculaire
- Maladies et anomalies congénitales, héréditaires et néonatales
- Maladies de la peau et du tissu conjonctif
- Angiœdème
- Angiœdème, héréditaire
- Angiœdème héréditaire de types I et II
Autres numéros d'identification d'étude
- PHA022121-C301
- 2021-000227-13 (Numéro EudraCT)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
NON
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Oui
Étudie un produit d'appareil réglementé par la FDA américaine
Non
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