Study of Oral Deucrictibant XR Tablet for Prophylaxis and Deucrictibant Soft Capsule for On-Demand Treatment of Angioedema Attacks in Adults With Acquired Angioedema Due to C1 Inhibitor Deficiency (CREAATE)
A Phase 3, Randomized, Double-blind, Placebo-controlled, 3-Part Study to Evaluate the Efficacy and Safety of Orally Administered Deucrictibant XR Tablet for Prophylaxis and Deucrictibant Soft Capsule for On-demand Treatment of Angioedema Attacks in Adults With Acquired Angioedema Due to C1 Inhibitor Deficiency
This is a Phase 3, multicenter, 3-part study, with 2 randomized, double-blind, placebo-controlled parts and an open-label extension part, to evaluate the efficacy and safety of orally administered deucrictibant XR tablet for prophylaxis, and deucrictibant soft capsule for on-demand treatment of angioedema attacks in adult participants aged ≥ 18 years with AAE-C1INH.
Aperçu de l'étude
Statut
Intervention / Traitement
Description détaillée
The study consists of a Screening Period, during which eligibility is confirmed, a Part 1 Prophylaxis Double-blind Treatment Phase, a Part 2 On-demand, Double-blind Treatment Phase, and a Part 3 On-demand Open-label Extension Phase. Approximately 24 participants will be randomized in Part 1 into 2 parallel arms for a treatment period of 12 weeks. During the prophylaxis treatment period participants will receive blinded study drug (deucrictibant 40 mg XR or placebo randomized in a 1:1 ratio). Upon completion of Part 1, participants will roll-over into Part 2. In addition to rollover participants completing Part 1, new deucrictibant treatment-naïve participants will be enrolled directly into Part 2 and this may occur while Part 1 is ongoing. During the on-demand period participants will receive blinded study drug (deucrictibant 20 mg soft capsule or matching placebo randomized in a 1:1 ratio, 2-period, 2-treatment crossover design) for 2 qualifying AAE-C1INH attacks. Participants completing Part 2 may roll over into Part 3 where all AAE-C1INH attacks will be treated with open-label deucrictibant 20 mg soft capsule.
Type d'étude
Inscription (Estimé)
Phase
- Phase 3
Contacts et emplacements
Coordonnées de l'étude
- Nom: Pharvaris Clinical Team
- Numéro de téléphone: 0031-712-036-410
- E-mail: clinicaltrials@pharvaris.com
Lieux d'étude
-
-
-
Berlin, Allemagne
- Recrutement
- Study Site
-
Frankfurt am Main, Allemagne
- Recrutement
- Study Site
-
Munich, Allemagne
- Recrutement
- Study Site
-
-
-
-
-
Clayton, Australie
- Recrutement
- Study Site
-
-
-
-
-
Sofia, Bulgarie
- Recrutement
- Study Site
-
-
-
-
-
Edmonton, Canada
- Recrutement
- Study Site
-
-
-
-
-
Madrid, Espagne
- Recrutement
- Study Site
-
-
-
-
-
Grenoble, France
- Recrutement
- Study Site
-
Lille, France
- Recrutement
- Study Site
-
Paris, France
- Recrutement
- Study Site
-
-
-
-
-
Budapest, Hongrie
- Recrutement
- Study Site
-
-
-
-
-
Milan, Italie
- Recrutement
- Study Site 1
-
Milan, Italie
- Recrutement
- Study Site 2
-
Milan, Italie
- Recrutement
- Study Site 3
-
Padova, Italie
- Recrutement
- Study Site
-
Roma, Italie
- Recrutement
- Study Site
-
-
-
-
-
Vienna, L'Autriche
- Recrutement
- Study Site
-
-
-
-
-
Auckland, Nouvelle-Zélande
- Recrutement
- Study Site
-
-
-
-
-
Amsterdam, Pays-Bas
- Recrutement
- Study Site
-
-
-
-
-
Krakow, Pologne
- Recrutement
- Study Site
-
-
-
-
-
Bristol, Royaume-Uni
- Recrutement
- Study Site
-
Cambridge, Royaume-Uni
- Recrutement
- Study Site
-
Leicester, Royaume-Uni
- Recrutement
- Study Site
-
London, Royaume-Uni
- Recrutement
- Study Site
-
Newcastle upon Tyne, Royaume-Uni
- Recrutement
- Study Site
-
Plymouth, Royaume-Uni
- Recrutement
- Study Site
-
-
-
-
-
Basel, Suisse
- Recrutement
- Study Site
-
-
-
-
-
Ankara, Turquie (Türkiye)
- Recrutement
- Study Site
-
-
-
-
California
-
San Diego, California, États-Unis, 92093
- Recrutement
- Study Site
-
Walnut Creek, California, États-Unis, 94598,
- Recrutement
- Study Site
-
-
Missouri
-
St Louis, Missouri, États-Unis, 63130
- Recrutement
- Study Site
-
-
Pennsylvania
-
Hershey, Pennsylvania, États-Unis, 17033
- Recrutement
- Study Site
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Provision of written informed consent
- Male or female (sex at birth) aged ≥18 years
- Diagnosis of AAE-C1INH
- History of AAE-C1INH attacks prior to the Screening Visit.
- If underlying disease associated with AAE is present, the underlying disease must be stable throughout the duration of part 1.
- Reliable access and ability to use available therapy to effectively manage AAE- C1INH attacks.
- Female participants of childbearing potential must agree to the protocol-specified pregnancy testing and to be abstinent from heterosexual intercourse or to use an acceptable contraception method.
Females of non-childbearing potential (surgically sterile, or postmenopausal with ≥ 12 months amenorrhea and postmenopausal FSH confirmation) are not required to use contraception during the study.
• Capable of recording, without assistance, eDiary and ePRO data using an electronic device, as evidenced by the eDiary and ePRO training.
Exclusion Criteria:
- Participation in a clinical study with any other investigational drug within the last 30 days or within 5 half-lives of the investigational drug at the Screening Visit (whichever is longer).
- Receiving long-term prophylaxis (LTP) treatment for AAE-C1INH and satisfied with this treatment. Participants who are not satisfied (eg, tolerability issues, lack of efficacy) and have previously stopped LTP treatment for AAE-C1INH, for reasons other than participation in this study, can sign the ICF and begin the Screening Period only if their last dose of the treatment was received prior to the timepoint before the Screening Visit
- Any females who are pregnant, plan to become pregnant, or are currently breast-feeding
- Abnormal hepatic function
- Moderate or severe renal impairment
- Any clinically significant comorbidity or systemic dysfunction that would interfere with the participant's safety or ability to participate in the study.
- History of epilepsy and/or other significant neurological diseases
- Any clinically significant and uncontrolled gastrointestinal dysfunction that may impact study drug absorption
- Evidence of current alcohol or drug abuse
- Use of medications that are moderate and strong inhibitors of cytochrome P450 (CYP) 3A4, or strong inducers of CYP3A4 within the last 30 days or within 5 half-lives (whichever is longer) at the time of the Screening Visit
- Known hypersensitivity to deucrictibant or any of the excipients of the study drug
- Use of angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption within 5 half-lives before the Screening Visit
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Partie 1 - Bras 1 - Actif
|
Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use Part 2: Deucrictibant 20 mg soft capsule oral use Part 3: Deucrictibant 20 mg soft capsule oral use |
|
Comparateur placebo: Partie 1 - Bras 2 - Placebo
|
Part 1: Placebo Comparator tablet for once daily oral use Part 2: Placebo Comparator soft capsule oral use |
|
Expérimental: Partie 2 - Bras 1
|
Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use Part 2: Deucrictibant 20 mg soft capsule oral use Part 3: Deucrictibant 20 mg soft capsule oral use Part 1: Placebo Comparator tablet for once daily oral use Part 2: Placebo Comparator soft capsule oral use |
|
Expérimental: Partie 2 - Bras 2
|
Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use Part 2: Deucrictibant 20 mg soft capsule oral use Part 3: Deucrictibant 20 mg soft capsule oral use Part 1: Placebo Comparator tablet for once daily oral use Part 2: Placebo Comparator soft capsule oral use |
|
Expérimental: Partie 3 - Ouverte
|
Part 1: Deucrictibant 40 mg extended-release tablet for once daily oral use Part 2: Deucrictibant 20 mg soft capsule oral use Part 3: Deucrictibant 20 mg soft capsule oral use |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
|---|---|
|
Part 1: Time-normalized number of Investigator-confirmed AAE-C1INH attacks during Treatment Phase
Délai: 12 weeks
|
12 weeks
|
|
Part 2: Time to symptom relief, Patient Global Impression of Change (PGI-C) rating of at least "better"
Délai: 12 hours post-treatment
|
12 hours post-treatment
|
|
Part 3: Incidence of treatment-emergent adverse events (TEAEs), treatment-emergent adverse events of special interest (AESIs), and serious adverse events (SAEs)
Délai: Through study termination, an average of 36 weeks
|
Through study termination, an average of 36 weeks
|
|
Part 3: Number of participants with clinically significant changes from baseline in Hematology parameters
Délai: Through study termination, an average of 36 weeks
|
Through study termination, an average of 36 weeks
|
|
Part 3: Number of participants with clinically significant changes from baseline in Urinalysis parameters
Délai: Through study termination, an average of 36 weeks
|
Through study termination, an average of 36 weeks
|
|
Part 3: Number of participants with clinically significant changes from baseline in Biochemistry parameters
Délai: Through study termination, an average of 36 weeks
|
Through study termination, an average of 36 weeks
|
|
Part 3: Number of participants with clinically significant changes from baseline in vital signs
Délai: Through study termination, an average of 36 weeks
|
Through study termination, an average of 36 weeks
|
|
Part 3: Number of participants with clinically significant changes from baseline in physical examinations
Délai: Through study termination, an average of 36 weeks
|
Through study termination, an average of 36 weeks
|
|
Part 3: Number of participants with clinically significant changes in electrocardiogram (ECG)
Délai: Through study termination, an average of 36 weeks
|
Through study termination, an average of 36 weeks
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Part 1: Proportion of participants who are AAE-C1INH attack-free during Treatment Phase
Délai: 12 weeks
|
12 weeks
|
|
|
Part 1: Time-normalized number of Investigator-confirmed AAE-C1INH attacks treated with on-demand medication during Treatment Phase
Délai: 12 weeks
|
12 weeks
|
|
|
Part 1: Time-normalized number of Investigator-confirmed moderate or severe AAE-C1INH attacks during Treatment Phase
Délai: 12 weeks
|
12 weeks
|
|
|
Part 1: Time-normalized number of Investigator-confirmed severe AAE-C1INH attacks during Treatment Phase
Délai: 12 weeks
|
12 weeks
|
|
|
Part 1: Proportion of participants achieving ≥50%, ≥70% and ≥90% reduction in AAE-C1NH attack rate relative to baseline during Treatment Phase
Délai: 12 weeks
|
12 weeks
|
|
|
Part 1: Incidence of TEAEs, treatment-emergent AESIs, and SAEs
Délai: 12 weeks
|
12 weeks
|
|
|
Part 1: Number of participants with clinically significant changes from baseline in Hematology parameters
Délai: 12 weeks
|
12 weeks
|
|
|
Part 1: Number of participants with clinically significant changes from baseline in Urinalysis parameters
Délai: 12 weeks
|
12 weeks
|
|
|
Part 1: Number of participants with clinically significant changes from baseline in Biochemistry parameters
Délai: 12 weeks
|
12 weeks
|
|
|
Part 1: Number of participants with clinically significant changes from baseline in Vital signs
Délai: 12 weeks
|
12 weeks
|
|
|
Part 1: Number of participants with clinically significant changes from baseline in physical examination
Délai: 12 weeks
|
12 weeks
|
|
|
Part 1: Number of participants with clinically significant changes from baseline in ECG parameters
Délai: 12 weeks
|
12 weeks
|
|
|
Part 1: Pre-dose plasma concentrations of Deucrictibant
Délai: At Weeks 6 and 12
|
Deucrictibant plasma concentrations will be analyzed using liquid chromatography-mass spectrometry/mass spectrometry methods |
At Weeks 6 and 12
|
|
Part 1: Pre-dose plasma concentrations of deucrictibant metabolites
Délai: At Weeks 6 and 12
|
Deucrictibant metabolites plasma concentrations will be analyzed using liquid chromatography-mass spectrometry/mass spectrometry methods |
At Weeks 6 and 12
|
|
Part 1: Pharmacokinetics [PK]: Urine concentrations of Deucrictibant and deucrictibant metabolites
Délai: At Week 12
|
At Week 12
|
|
|
Part 1: Change from baseline in Angioedema Quality of Life (AE-QoL) questionnaire total score, functioning domain score, and fears/shame domain score
Délai: Baseline (Day 1) and at Weeks 4, 8 and 12
|
The AE-QoL is a short 17-item questionnaire designed to retrospectively assess HRQoL, with a recall period of 4 weeks. Its results can be displayed as a total score or as 4 domain scores. The scores range from 0 to 100, after linear transformation of raw values, with higher scores indicating higher HRQoL impairment. |
Baseline (Day 1) and at Weeks 4, 8 and 12
|
|
Part 1: Change from baseline in Angioedema Control Test 4-week version (AECT-4wk)
Délai: Baseline (Day 1) and at Week 12
|
AECT-4wk measures disease control retrospectively, it comprises 4 questions over a 4-week recall period. Scores for the responses in the AECT range from 0 to 16, with higher scores indicating better disease control (≤ 9 poorly controlled; ≥ 10 well controlled) |
Baseline (Day 1) and at Week 12
|
|
Part 1: Patient Global Assessment-Status (PGA-S) at baseline
Délai: At Baseline (Day 1)
|
PGA-Status assesses on a 5-point scale how the participant's QoL has been impacted by AAE-C1INH since start taking the study drug |
At Baseline (Day 1)
|
|
Part 1: Patient Global Assessment of Change (PGA-Change) at Week 12
Délai: At Week 12
|
PGA-Change assesses on a 5-point scale how the participant's QoL has been impacted by AAE-C1INH since start taking the study drug |
At Week 12
|
|
Part 1: Change from baseline in EuroQol 5 Dimension 5 level (EQ 5D 5L)
Délai: Baseline (Day 1) and at Week 12
|
EQ 5D 5L is a brief, multiattribute, generic, health status measure composed of 5 questions with Likert response options (descriptive system) and a visual analog scale (EQ-VAS). The latter asks patients to rate their own health from 0 to 100 (the worst and best imaginable health, respectively) |
Baseline (Day 1) and at Week 12
|
|
Part 2: Time to complete symptom resolution, Patient Global Impression of Severity (PGI-S) rating of "no symptoms
Délai: sustained within 24 hours post-treatment
|
sustained within 24 hours post-treatment
|
|
|
Part 2: Time to symptom relief defined as PGI-S rating of at least 1 point reduction
Délai: 12 hours post-treatment
|
12 hours post-treatment
|
|
|
Part 2: Proportion of study drug-treated attacks achieving complete symptom resolution defined as achieving PGI- S rating of "no symptoms"
Délai: At 24 hours post-treatment
|
At 24 hours post-treatment
|
|
|
Part 2: Time to onset of symptom relief, defined as PGI-C rating of at least "a little better"
Délai: Within 12 hours post-treatment
|
Within 12 hours post-treatment
|
|
|
Part 2: Time to End of Progression (EoP) in attack symptoms
Délai: Within 12 hours post-treatment
|
EOP is defined as the earliest post-treatment timepoint after which all subsequent PGI-C ratings are stable or improved |
Within 12 hours post-treatment
|
|
Part 2: Incidence of TEAEs, treatment-emergent AESIs, and SAEs
Délai: Up to 24 weeks
|
Up to 24 weeks
|
|
|
Part 2: Number of participants with clinically significant changes from baseline in Hematology parameters
Délai: 24 weeks
|
24 weeks
|
|
|
Part 2: Number of participants with clinically significant changes from baseline in Urinalysis parameters
Délai: 24 weeks
|
24 weeks
|
|
|
Part 2: Number of participants with clinically significant changes from baseline in Biochemistry parameters
Délai: 24 weeks
|
24 weeks
|
|
|
Part 2: Number of participants with clinically significant changes from baseline in Vital signs
Délai: 24 weeks
|
24 weeks
|
|
|
Part 2: Number of participants with clinically significant changes from baseline in physical examination
Délai: 24 weeks
|
24 weeks
|
|
|
Part 2: Number of participants with clinically significant changes from baseline in ECG parameters
Délai: 24 weeks
|
24 weeks
|
|
|
Part 2: Pharmacokinetics [PK]: Deucrictibant and deucrictibant metabolites plasma concentration-time profiles
Délai: Day 1
|
Day 1
|
|
|
Part 3: Time to symptom relief, as PGI-C rating of at least "better"
Délai: 12 hours post-treatment
|
12 hours post-treatment
|
|
|
Part 3: Time to symptom relief, as PGI-S rating of at least 1 point reduction
Délai: 12 hours post-treatment
|
12 hours post-treatment
|
|
|
Part 3: Proportion of study drug-treated attacks achieving complete symptom resolution, defined as achieving PGI-S rating of "no symptoms"
Délai: 24 hours post-treatment
|
24 hours post-treatment
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Directeur d'études: Study Director, Pharvaris, Pharvaris Netherlands B.V.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Maladies héréditaires de déficience du complément
- Maladies d'immunodéficience primaire
- Maladies vasculaires
- Maladies cardiovasculaires
- Maladies génétiques, innées
- Maladies du système immunitaire
- Hypersensibilité immédiate
- Hypersensibilité
- Syndromes d'immunodéficience
- Maladies de la peau
- Urticaire
- Maladies de la peau, vasculaire
- Maladies et anomalies congénitales, héréditaires et néonatales
- Maladies de la peau et du tissu conjonctif
- Angiœdème
- Angiœdème, héréditaire
- Angio-œdème acquis
Autres numéros d'identification d'étude
- PHA022121-C308
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .