Estudio de rango de dosis de PHA-022121 oral para la profilaxis contra ataques de angioedema en pacientes con angioedema hereditario tipo I o tipo II (HAE CHAPTER-1)
12 de agosto de 2026 actualizado por: Pharvaris Netherlands B.V.
Un estudio de fase II, doble ciego, controlado con placebo, aleatorizado, de rango de dosis, de grupos paralelos para evaluar la seguridad y la eficacia de PHA-022121 administrado por vía oral para la profilaxis contra los ataques de angioedema en pacientes con angioedema hereditario debido a la deficiencia del inhibidor de C1 ( Tipo I o Tipo II)
Este estudio evalúa la seguridad y eficacia de PHA-022121 administrado por vía oral para la profilaxis de ataques de angioedema en pacientes con angioedema hereditario (AEH).
El estudio consta de 2 partes, con pacientes que completan su participación en la Parte 1 antes de iniciar el tratamiento en la Parte 2. La Parte 1 del estudio tiene 3 brazos paralelos y aproximadamente 30 pacientes serán igualmente aleatorizados a uno de los dos regímenes de dosis de PHA-022121 o un placebo equivalente.
Los pacientes continuarán con el brazo único de etiqueta abierta en la Parte 2 del estudio después de completar la Parte 1.
El período de selección es de hasta 8 semanas y los períodos de tratamiento son de 12 semanas (Parte 1) y 50 semanas (Parte 2) de duración.
Descripción general del estudio
Estado
Terminado
Condiciones
- Angioedema hereditario
- Angioedema hereditario tipo I
- Angioedema Hereditario Tipo II
- Angioedema Hereditario Tipos I y II
- Ataque de angioedema hereditario
- Angioedema hereditario con deficiencia del inhibidor de la esterasa C1
- Angioedema hereditario - Tipo 1
- Angioedema hereditario - Tipo 2
- Deficiencia del inhibidor de la esterasa C1
- Deficiencia del inhibidor C1
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
34
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Berlin, Alemania, 10117
- Study Site
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Frankfurt, Alemania, 60323
- Study Site
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Vienna, Austria, A-1090
- Study Site
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Sofia, Bulgaria, 1680
- Study Site
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Ontario
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Ottawa, Ontario, Canadá, K1H 1E4
- Study Site
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Quebec
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Montreal, Quebec, Canadá, H2W 1R7
- Study Site
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Alabama
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Birmingham, Alabama, Estados Unidos, 35209
- Study Site
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Arizona
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Paradise Valley, Arizona, Estados Unidos, 85253
- Study Site
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Missouri
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St Louis, Missouri, Estados Unidos, 63141
- Study Site
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Dublin, Irlanda, D08NHY1
- Study Site
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Milan, Italia, 20157
- Study Site
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Palermo, Italia, 0146
- Study Site
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PD
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Padua, PD, Italia, 35128
- Study Site
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Krakow, Polonia
- Study Site
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England
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Brighton, England, Reino Unido, BN2 1ES
- Study Site
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Bristol, England, Reino Unido, BS10 5NB
- Study Site
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Cambridge, England, Reino Unido, CB2 0QQ
- Study Site
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London, England, Reino Unido, E1 1FR
- Study Site
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Southampton, England, Reino Unido, SO16 6YD
- Study Site
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años a 75 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Descripción
Criterios de inclusión:
- Formulario de consentimiento informado firmado y fechado
- Diagnóstico de AEH tipo I o II
- Historial documentado de al menos 3 ataques de AEH en los últimos 3 meses consecutivos antes de la selección, o un mínimo de 2 ataques de AEH durante el período de selección
- Acceso confiable y experiencia para usar medicamentos estándar para ataques agudos
Criterio de exclusión:
- Embarazo o lactancia
- Electrocardiograma anormal clínicamente significativo
- Cualquier otra enfermedad sistémica o enfermedad o trastorno significativo que pudiera interferir con la seguridad o la capacidad del paciente para participar en el estudio.
- Uso de inhibidores de la esterasa C1, inhibidores orales de la calicreína, andrógenos atenuados, antifibrinolíticos o terapia de AEH monoclonal dentro de un período definido antes de la inscripción
- Función hepática anormal
- Función renal anormal
- Historial de abuso de alcohol o drogas dentro de un período definido, o evidencia actual de dependencia o abuso de sustancias
- Participación en cualquier otro estudio de fármaco en investigación dentro de un período definido
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Prevención
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Comparador de placebos: Parte 1: Placebo
BID placebo
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Cápsulas de placebo a juego para uso oral
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Experimental: Parte 1: dosis baja
BID dosis baja de deucrictibant
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Cápsulas blandas de deucrictibant para uso oral (PHVS416)
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Experimental: Parte 1: dosis alta
BID dosis alta de deucrictibant
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Cápsulas blandas de deucrictibant para uso oral (PHVS416)
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Experimental: Parte 2: etiqueta abierta
BID dosis alta de deucrictibant
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Cápsulas blandas de deucrictibant para uso oral (PHVS416)
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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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
Periodo de tiempo: 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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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Number of Investigator-confirmed Moderate or Severe HAE Attacks During the Treatment Period in Part 1
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Marc Riedl, MD, UC San Diego, La Jolla, California, United States
- Investigador principal: Emel Aygören-Pürsün, MD, University Hospital Frankfurt - Goethe University, Frankfurt, Germany
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
19 de abril de 2022
Finalización primaria (Actual)
30 de junio de 2025
Finalización del estudio (Actual)
30 de junio de 2025
Fechas de registro del estudio
Enviado por primera vez
7 de septiembre de 2021
Primero enviado que cumplió con los criterios de control de calidad
7 de septiembre de 2021
Publicado por primera vez (Actual)
17 de septiembre de 2021
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
17 de agosto de 2026
Última actualización enviada que cumplió con los criterios de control de calidad
12 de agosto de 2026
Última verificación
1 de agosto de 2026
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades hereditarias por deficiencia del complemento
- Enfermedades de inmunodeficiencia primaria
- Enfermedades Vasculares
- Enfermedades cardiovasculares
- Enfermedades Genéticas Congénitas
- Enfermedades del sistema inmunológico
- Hipersensibilidad, Inmediata
- Hipersensibilidad
- Síndromes de deficiencia inmunológica
- Enfermedades de la piel
- Urticaria
- Enfermedades De La Piel Vasculares
- Enfermedades y anomalías congénitas, hereditarias y neonatales
- Enfermedades de la piel y del tejido conectivo
- Angioedema
- Angioedemas Hereditarios
- Angioedema Hereditario Tipos I y II
Otros números de identificación del estudio
- PHA022121-C301
- 2021-000227-13 (Número EudraCT)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Sí
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
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