Estudo de variação de dose de PHA-022121 oral para profilaxia contra ataques de angioedema em pacientes com angioedema hereditário tipo I ou tipo II (HAE CHAPTER-1)
12 de agosto de 2026 atualizado por: Pharvaris Netherlands B.V.
Um estudo de fase II, duplo-cego, controlado por placebo, randomizado, com variação de dose, grupo paralelo para avaliar a segurança e a eficácia do PHA-022121 administrado por via oral para profilaxia contra ataques de angioedema em pacientes com angioedema hereditário devido à deficiência de inibidor de C1 ( Tipo I ou Tipo II)
Este estudo avalia a segurança e eficácia do PHA-022121 administrado por via oral para profilaxia contra ataques de angioedema em pacientes com angioedema hereditário (HAE).
O estudo consiste em 2 partes, com os pacientes concluindo a participação na Parte 1 antes do início do tratamento na Parte 2. A Parte 1 do estudo tem 3 braços paralelos e aproximadamente 30 pacientes serão igualmente randomizados para um dos dois regimes de dosagem de PHA-022121 ou placebo correspondente.
Os pacientes continuarão para o único braço aberto na Parte 2 do estudo após a conclusão da Parte 1.
O período de triagem é de até 8 semanas e os períodos de tratamento são de 12 semanas (Parte 1) e 50 semanas (Parte 2) de duração.
Visão geral do estudo
Status
Rescindido
Condições
- Angioedema Hereditário
- Angioedema Hereditário Tipo I
- Angioedema hereditário tipo II
- Angioedema hereditário tipos I e II
- Ataque de angioedema hereditário
- Angioedema hereditário com deficiência do inibidor da esterase C1
- Angioedema Hereditário - Tipo 1
- Angioedema Hereditário - Tipo 2
- Deficiência do Inibidor da Esterase C1
- Deficiência do Inibidor C1
Intervenção / Tratamento
Tipo de estudo
Intervencional
Inscrição (Real)
34
Estágio
- Fase 2
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Berlin, Alemanha, 10117
- Study Site
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Frankfurt, Alemanha, 60323
- Study Site
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Sofia, Bulgária, 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, Itália, 20157
- Study Site
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Palermo, Itália, 0146
- Study Site
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PD
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Padua, PD, Itália, 35128
- Study Site
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Krakow, Polônia
- 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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Vienna, Áustria, A-1090
- Study Site
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos a 75 anos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Descrição
Critério de inclusão:
- Formulário de consentimento informado assinado e datado
- Diagnóstico de AEH tipo I ou II
- Histórico documentado de pelo menos 3 ataques de HAE nos últimos 3 meses consecutivos antes da triagem, ou um mínimo de 2 ataques de HAE durante o período de triagem
- Acesso confiável e experiência para usar medicamentos padrão de tratamento para ataques agudos
Critério de exclusão:
- Gravidez ou amamentação
- Eletrocardiograma anormal clinicamente significativo
- Qualquer outra doença sistêmica ou doença ou distúrbio significativo que interfira na segurança do paciente ou na capacidade de participar do estudo
- Uso de inibidor de C1-esterase, inibidores orais de calicreína, andrógenos atenuados, antifibrinolíticos ou terapia monoclonal de HAE dentro de um período definido antes da inscrição
- Função hepática anormal
- Função renal anormal
- História de abuso de álcool ou drogas dentro de um período definido, ou evidência atual de dependência ou abuso de substâncias
- Participação em qualquer outro estudo de medicamento experimental dentro do período definido
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Prevenção
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Comparador de Placebo: Parte 1: Placebo
BID placebo
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Cápsulas de placebo correspondentes para uso oral
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Experimental: Parte 1: Dose baixa
BID baixa dose de deucritibant
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Deucrictibant cápsulas moles para uso oral (PHVS416)
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Experimental: Parte 1: Dose alta
BID alta dose de deucritibant
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Deucrictibant cápsulas moles para uso oral (PHVS416)
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Experimental: Parte 2: rótulo aberto
BID alta dose de deucritibant
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Deucrictibant cápsulas moles para uso oral (PHVS416)
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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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
Prazo: 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 resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Number of Investigator-confirmed Moderate or Severe HAE Attacks During the Treatment Period in Part 1
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
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
Publicações e links úteis
A pessoa responsável por inserir informações sobre o estudo fornece voluntariamente essas publicações. Estes podem ser sobre qualquer coisa relacionada ao estudo.
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo (Real)
19 de abril de 2022
Conclusão Primária (Real)
30 de junho de 2025
Conclusão do estudo (Real)
30 de junho de 2025
Datas de inscrição no estudo
Enviado pela primeira vez
7 de setembro de 2021
Enviado pela primeira vez que atendeu aos critérios de CQ
7 de setembro de 2021
Primeira postagem (Real)
17 de setembro de 2021
Atualizações de registro de estudo
Última Atualização Postada (Real)
17 de agosto de 2026
Última atualização enviada que atendeu aos critérios de controle de qualidade
12 de agosto de 2026
Última verificação
1 de agosto de 2026
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças por Deficiência de Complemento Hereditário
- Doenças de Imunodeficiência Primária
- Doenças Vasculares
- Doenças cardiovasculares
- Doenças Genéticas, Congênitas
- Doenças do sistema imunológico
- Hipersensibilidade, Imediata
- Hipersensibilidade
- Síndromes de Deficiência Imunológica
- Doenças de pele
- Urticária
- Doenças de Pele, Vasculares
- Doenças e Anormalidades Congênitas, Hereditárias e Neonatais
- Doenças da Pele e do Tecido Conjuntivo
- Angioedema
- Angioedemas Hereditários
- Angioedema hereditário tipos I e II
Outros números de identificação do estudo
- PHA022121-C301
- 2021-000227-13 (Número EudraCT)
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
NÃO
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Sim
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Não
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