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Dosisbereikstudie van orale PHA-022121 voor profylaxe tegen angio-oedeemaanvallen bij patiënten met erfelijk angio-oedeem type I of type II (HAE CHAPTER-1)

12 augustus 2026 bijgewerkt door: Pharvaris Netherlands B.V.

Een fase II, dubbelblind, placebogecontroleerd, gerandomiseerd, dosis-variërend, parallelle groepsonderzoek om de veiligheid en werkzaamheid te evalueren van PHA-022121 oraal toegediend voor profylaxe tegen angio-oedeemaanvallen bij patiënten met erfelijk angio-oedeem als gevolg van C1-remmerdeficiëntie ( Type I of Type II)

Deze studie evalueert de veiligheid en werkzaamheid van PHA-022121, oraal toegediend als profylaxe tegen angio-oedeemaanvallen bij patiënten met erfelijk angio-oedeem (HAE). De studie bestaat uit 2 delen, waarbij patiënten deelname aan deel 1 voltooien voordat de behandeling in deel 2 wordt gestart. Deel 1 van de studie heeft 3 parallelle armen en ongeveer 30 patiënten zullen gelijkelijk worden toegewezen aan een van de twee doseringsregimes van PHA-022121 of overeenkomende placebo. Patiënten gaan na voltooiing van deel 1 door naar de enkele open-labelarm in deel 2 van het onderzoek. De screeningperiode duurt maximaal 8 weken en de behandelingsperioden duren 12 weken (deel 1) en 50 weken (deel 2).

Studie Overzicht

Toestand

Beëindigd

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Werkelijk)

34

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Bulgarije
      • Sofia, Bulgarije, 1680
        • Study Site
  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1H 1E4
        • Study Site
    • Quebec
      • Montreal, Quebec, Canada, H2W 1R7
        • Study Site
  • Duitsland
      • Berlin, Duitsland, 10117
        • Study Site
      • Frankfurt, Duitsland, 60323
        • Study Site
  • Ierland
      • Dublin, Ierland, D08NHY1
        • Study Site
  • Italië
      • Milan, Italië, 20157
        • Study Site
      • Palermo, Italië, 0146
        • Study Site
    • PD
      • Padua, PD, Italië, 35128
        • Study Site
  • Oostenrijk
      • Vienna, Oostenrijk, A-1090
        • Study Site
  • Polen
      • Krakow, Polen
        • Study Site
  • Verenigd Koninkrijk
    • England
      • Brighton, England, Verenigd Koninkrijk, BN2 1ES
        • Study Site
      • Bristol, England, Verenigd Koninkrijk, BS10 5NB
        • Study Site
      • Cambridge, England, Verenigd Koninkrijk, CB2 0QQ
        • Study Site
      • London, England, Verenigd Koninkrijk, E1 1FR
        • Study Site
      • Southampton, England, Verenigd Koninkrijk, SO16 6YD
        • Study Site
  • Verenigde Staten
    • Alabama
      • Birmingham, Alabama, Verenigde Staten, 35209
        • Study Site
    • Arizona
      • Paradise Valley, Arizona, Verenigde Staten, 85253
        • Study Site
    • Missouri
      • St Louis, Missouri, Verenigde Staten, 63141
        • Study Site

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 75 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Beschrijving

Inclusiecriteria:

  • Ondertekend en gedateerd toestemmingsformulier
  • Diagnose van HAE type I of II
  • Gedocumenteerde geschiedenis van ten minste 3 HAE-aanvallen in de laatste 3 opeenvolgende maanden voorafgaand aan de screening, of minimaal 2 HAE-aanvallen tijdens de screeningperiode
  • Betrouwbare toegang tot en ervaring met het gebruik van standaardmedicatie voor acute aanvallen

Uitsluitingscriteria:

  • Zwangerschap of borstvoeding
  • Klinisch significant abnormaal elektrocardiogram
  • Elke andere systemische ziekte of significante ziekte of stoornis die de veiligheid van de patiënt of het vermogen om aan het onderzoek deel te nemen zou kunnen verstoren
  • Gebruik van C1-esteraseremmer, orale kallikreïneremmers, verzwakte androgenen, antifibrinolytica of monoklonale HAE-therapie binnen een bepaalde periode voorafgaand aan inschrijving
  • Abnormale leverfunctie
  • Abnormale nierfunctie
  • Geschiedenis van alcohol- of drugsmisbruik binnen een bepaalde periode, of actueel bewijs van afhankelijkheid of misbruik van middelen
  • Deelname aan een ander experimenteel geneesmiddelenonderzoek binnen een bepaalde periode

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Preventie
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Verviervoudigen

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Placebo-vergelijker: Deel 1: Placebo
BID-placebo
Geneesmiddel: Placebo
Bijpassende placebocapsules voor oraal gebruik
Experimenteel: Deel 1: Lage dosis
BID lage dosis deucrictibant
Geneesmiddel: Deucrictibant lage dosis
Deucrictibant softgelcapsules voor oraal gebruik (PHVS416)
Experimenteel: Deel 1: Hoge dosis
BID hoge dosis deucrictibant
Geneesmiddel: Deucrictibant hoge dosis
Deucrictibant softgelcapsules voor oraal gebruik (PHVS416)
Experimenteel: Deel 2: Open-label
BID hoge dosis deucrictibant
Geneesmiddel: Deucrictibant hoge dosis
Deucrictibant softgelcapsules voor oraal gebruik (PHVS416)

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
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
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of Investigator-confirmed Moderate or Severe HAE Attacks During the Treatment Period in Part 1
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Pharvaris Netherlands B.V.

Onderzoekers

  • Hoofdonderzoeker: Marc Riedl, MD, UC San Diego, La Jolla, California, United States
  • Hoofdonderzoeker: Emel Aygören-Pürsün, MD, University Hospital Frankfurt - Goethe University, Frankfurt, Germany

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

19 april 2022

Primaire voltooiing (Werkelijk)

30 juni 2025

Studie voltooiing (Werkelijk)

30 juni 2025

Studieregistratiedata

Eerst ingediend

7 september 2021

Eerst ingediend dat voldeed aan de QC-criteria

7 september 2021

Eerst geplaatst (Werkelijk)

17 september 2021

Updates van studierecords

Laatste update geplaatst (Werkelijk)

17 augustus 2026

Laatste update ingediend die voldeed aan QC-criteria

12 augustus 2026

Laatst geverifieerd

1 augustus 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • PHA022121-C301
  • 2021-000227-13 (EudraCT-nummer)

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Ja

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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