Dosisfindungsstudie zu oralem PHA-022121 zur Prophylaxe gegen Angioödem-Attacken bei Patienten mit hereditärem Angioödem Typ I oder Typ II (HAE CHAPTER-1)
12. August 2026 aktualisiert von: Pharvaris Netherlands B.V.
Eine doppelblinde, Placebo-kontrollierte, randomisierte Parallelgruppen-Dosisfindungsstudie der Phase II zur Bewertung der Sicherheit und Wirksamkeit von oral verabreichtem PHA-022121 zur Prophylaxe gegen Angioödem-Attacken bei Patienten mit hereditärem Angioödem aufgrund von C1-Inhibitor-Mangel ( Typ I oder Typ II)
Diese Studie bewertet die Sicherheit und Wirksamkeit von oral verabreichtem PHA-022121 zur Prophylaxe gegen Angioödem-Attacken bei Patienten mit hereditärem Angioödem (HAE).
Die Studie besteht aus 2 Teilen, wobei die Patienten die Teilnahme an Teil 1 vor Beginn der Behandlung in Teil 2 abschließen. Teil 1 der Studie hat 3 parallele Arme und ungefähr 30 Patienten werden zu gleichen Teilen randomisiert einem von zwei Dosierungsschemata von PHA-022121 zugeteilt oder passendes Placebo.
Die Patienten werden nach Abschluss von Teil 1 mit dem einzelnen offenen Arm in Teil 2 der Studie fortfahren.
Der Screening-Zeitraum beträgt bis zu 8 Wochen und die Behandlungszeiträume 12 Wochen (Teil 1) und 50 Wochen (Teil 2).
Studienübersicht
Status
Beendet
Bedingungen
- Hereditäres Angioödem
- Hereditäres Angioödem Typ I
- Hereditäres Angioödem Typ II
- Hereditäres Angioödem Typ I und II
- Hereditärer Angioödem-Angriff
- Hereditäres Angioödem mit C1-Esterase-Inhibitor-Mangel
- Hereditäres Angioödem – Typ 1
- Hereditäres Angioödem – Typ 2
- C1-Esterase-Inhibitor-Mangel
- C1-Inhibitor-Mangel
Intervention / Behandlung
Studientyp
Interventionell
Einschreibung (Tatsächlich)
34
Phase
- Phase 2
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
-
-
-
Sofia, Bulgarien, 1680
- Study Site
-
-
-
-
-
Berlin, Deutschland, 10117
- Study Site
-
Frankfurt, Deutschland, 60323
- Study Site
-
-
-
-
-
Dublin, Irland, D08NHY1
- Study Site
-
-
-
-
-
Milan, Italien, 20157
- Study Site
-
Palermo, Italien, 0146
- Study Site
-
-
PD
-
Padua, PD, Italien, 35128
- Study Site
-
-
-
-
Ontario
-
Ottawa, Ontario, Kanada, K1H 1E4
- Study Site
-
-
Quebec
-
Montreal, Quebec, Kanada, H2W 1R7
- Study Site
-
-
-
-
-
Krakow, Polen
- Study Site
-
-
-
-
Alabama
-
Birmingham, Alabama, Vereinigte Staaten, 35209
- Study Site
-
-
Arizona
-
Paradise Valley, Arizona, Vereinigte Staaten, 85253
- Study Site
-
-
Missouri
-
St Louis, Missouri, Vereinigte Staaten, 63141
- Study Site
-
-
-
-
England
-
Brighton, England, Vereinigtes Königreich, BN2 1ES
- Study Site
-
Bristol, England, Vereinigtes Königreich, BS10 5NB
- Study Site
-
Cambridge, England, Vereinigtes Königreich, CB2 0QQ
- Study Site
-
London, England, Vereinigtes Königreich, E1 1FR
- Study Site
-
Southampton, England, Vereinigtes Königreich, SO16 6YD
- Study Site
-
-
-
-
-
Vienna, Österreich, A-1090
- Study Site
-
-
Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre bis 75 Jahre (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Beschreibung
Einschlusskriterien:
- Unterschriebene und datierte Einverständniserklärung
- Diagnose HAE Typ I oder II
- Dokumentierte Vorgeschichte von mindestens 3 HAE-Attacken innerhalb der letzten 3 aufeinanderfolgenden Monate vor dem Screening oder mindestens 2 HAE-Attacken während des Screening-Zeitraums
- Zuverlässiger Zugang und Erfahrung in der Anwendung von Standardmedikamenten für akute Attacken
Ausschlusskriterien:
- Schwangerschaft oder Stillzeit
- Klinisch signifikantes anormales Elektrokardiogramm
- Jede andere systemische Erkrankung oder signifikante Erkrankung oder Störung, die die Sicherheit oder Fähigkeit des Patienten zur Teilnahme an der Studie beeinträchtigen würde
- Verwendung von C1-Esterase-Inhibitoren, oralen Kallikrein-Inhibitoren, attenuierten Androgenen, Antifibrinolytika oder monoklonaler HAE-Therapie innerhalb eines definierten Zeitraums vor der Einschreibung
- Abnorme Leberfunktion
- Abnorme Nierenfunktion
- Vorgeschichte von Alkohol- oder Drogenmissbrauch innerhalb eines bestimmten Zeitraums oder aktuelle Hinweise auf Drogenabhängigkeit oder -missbrauch
- Teilnahme an einer anderen Arzneimittelstudie innerhalb eines festgelegten Zeitraums
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Verhütung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Vervierfachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Placebo-Komparator: Teil 1: Placebo
BID-Placebo
|
Passende Placebo-Kapseln zur oralen Anwendung
|
|
Experimental: Teil 1: Niedrige Dosis
BID niedrige Dosis Deucrictibant
|
Deucrictibant-Weichkapseln zur oralen Anwendung (PHVS416)
|
|
Experimental: Teil 1: Hochdosiert
Bieten Sie eine hohe Dosis Deucrictibant
|
Deucrictibant-Weichkapseln zur oralen Anwendung (PHVS416)
|
|
Experimental: Teil 2: Open-Label
Bieten Sie eine hohe Dosis Deucrictibant
|
Deucrictibant-Weichkapseln zur oralen Anwendung (PHVS416)
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
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
Zeitfenster: 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
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Number of Investigator-confirmed Moderate or Severe HAE Attacks During the Treatment Period in Part 1
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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
|
Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Ermittler
- Hauptermittler: Marc Riedl, MD, UC San Diego, La Jolla, California, United States
- Hauptermittler: Emel Aygören-Pürsün, MD, University Hospital Frankfurt - Goethe University, Frankfurt, Germany
Publikationen und hilfreiche Links
Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Tatsächlich)
19. April 2022
Primärer Abschluss (Tatsächlich)
30. Juni 2025
Studienabschluss (Tatsächlich)
30. Juni 2025
Studienanmeldedaten
Zuerst eingereicht
7. September 2021
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
7. September 2021
Zuerst gepostet (Tatsächlich)
17. September 2021
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
17. August 2026
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
12. August 2026
Zuletzt verifiziert
1. August 2026
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Erbliche Komplementmangelkrankheiten
- Primäre Immunschwächekrankheiten
- Gefäßerkrankungen
- Herz-Kreislauf-Erkrankungen
- Genetische Krankheiten, angeboren
- Erkrankungen des Immunsystems
- Überempfindlichkeit, sofort
- Überempfindlichkeit
- Immunologische Mangelsyndrome
- Hautkrankheiten
- Urtikaria
- Hautkrankheiten, Gefäß
- Angeborene, erbliche und neonatale Krankheiten und Anomalien
- Haut- und Bindegewebserkrankungen
- Angioödem
- Angioödeme, erblich
- Hereditäres Angioödem Typ I und II
Andere Studien-ID-Nummern
- PHA022121-C301
- 2021-000227-13 (EudraCT-Nummer)
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
NEIN
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Ja
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
Nein
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .