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.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Undersøgelsestype
Tilmelding (Anslået)
Tilmelding
Fase
Fase
- Fase 3
Kontakter og lokationer
Studiekontakt
Studiekontakt
- Navn: Pharvaris Clinical Team
- Telefonnummer: 0031-712-036-410
- E-mail: clinicaltrials@pharvaris.com
Studiesteder
-
-
-
Clayton, Australien
- Rekruttering
- Study Site
-
-
-
-
-
Sofia, Bulgarien
- Rekruttering
- Study Site
-
-
-
-
-
Edmonton, Canada
- Rekruttering
- Study Site
-
-
-
-
-
Bristol, Det Forenede Kongerige
- Rekruttering
- Study Site
-
Cambridge, Det Forenede Kongerige
- Rekruttering
- Study Site
-
Leicester, Det Forenede Kongerige
- Rekruttering
- Study Site
-
London, Det Forenede Kongerige
- Rekruttering
- Study Site
-
Newcastle upon Tyne, Det Forenede Kongerige
- Rekruttering
- Study Site
-
Plymouth, Det Forenede Kongerige
- Rekruttering
- Study Site
-
-
-
-
California
-
San Diego, California, Forenede Stater, 92093
- Rekruttering
- Study Site
-
Walnut Creek, California, Forenede Stater, 94598,
- Rekruttering
- Study Site
-
-
Missouri
-
St Louis, Missouri, Forenede Stater, 63130
- Rekruttering
- Study Site
-
-
Pennsylvania
-
Hershey, Pennsylvania, Forenede Stater, 17033
- Rekruttering
- Study Site
-
-
-
-
-
Grenoble, Frankrig
- Rekruttering
- Study Site
-
Lille, Frankrig
- Rekruttering
- Study Site
-
Paris, Frankrig
- Rekruttering
- Study Site
-
-
-
-
-
Amsterdam, Holland
- Rekruttering
- Study Site
-
-
-
-
-
Milan, Italien
- Rekruttering
- Study Site 1
-
Milan, Italien
- Rekruttering
- Study Site 2
-
Milan, Italien
- Rekruttering
- Study Site 3
-
Padova, Italien
- Rekruttering
- Study Site
-
Roma, Italien
- Rekruttering
- Study Site
-
-
-
-
-
Auckland, New Zealand
- Rekruttering
- Study Site
-
-
-
-
-
Krakow, Polen
- Rekruttering
- Study Site
-
-
-
-
-
Basel, Schweiz
- Rekruttering
- Study Site
-
-
-
-
-
Madrid, Spanien
- Rekruttering
- Study Site
-
-
-
-
-
Ankara, Tyrkiet (Türkiye)
- Rekruttering
- Study Site
-
-
-
-
-
Berlin, Tyskland
- Rekruttering
- Study Site
-
Frankfurt am Main, Tyskland
- Rekruttering
- Study Site
-
Munich, Tyskland
- Rekruttering
- Study Site
-
-
-
-
-
Budapest, Ungarn
- Rekruttering
- Study Site
-
-
-
-
-
Vienna, Østrig
- Rekruttering
- Study Site
-
-
Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
|---|---|
|
Eksperimentel: Del 1 - Arm 1 - Aktiv
|
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 |
|
Placebo komparator: Del 1 - Arm 2 - Placebo
|
Part 1: Placebo Comparator tablet for once daily oral use Part 2: Placebo Comparator soft capsule oral use |
|
Eksperimentel: Del 2 - Arm 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 |
|
Eksperimentel: Del 2 - Arm 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 |
|
Eksperimentel: Del 3 - Åbent mærket
|
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 |
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
|
Part 1: Time-normalized number of Investigator-confirmed AAE-C1INH attacks during Treatment Phase
Tidsramme: 12 weeks
|
12 weeks
|
|
Part 2: Time to symptom relief, Patient Global Impression of Change (PGI-C) rating of at least "better"
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: Through study termination, an average of 36 weeks
|
Through study termination, an average of 36 weeks
|
Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Part 1: Proportion of participants who are AAE-C1INH attack-free during Treatment Phase
Tidsramme: 12 weeks
|
12 weeks
|
|
|
Part 1: Time-normalized number of Investigator-confirmed AAE-C1INH attacks treated with on-demand medication during Treatment Phase
Tidsramme: 12 weeks
|
12 weeks
|
|
|
Part 1: Time-normalized number of Investigator-confirmed moderate or severe AAE-C1INH attacks during Treatment Phase
Tidsramme: 12 weeks
|
12 weeks
|
|
|
Part 1: Time-normalized number of Investigator-confirmed severe AAE-C1INH attacks during Treatment Phase
Tidsramme: 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
Tidsramme: 12 weeks
|
12 weeks
|
|
|
Part 1: Incidence of TEAEs, treatment-emergent AESIs, and SAEs
Tidsramme: 12 weeks
|
12 weeks
|
|
|
Part 1: Number of participants with clinically significant changes from baseline in Hematology parameters
Tidsramme: 12 weeks
|
12 weeks
|
|
|
Part 1: Number of participants with clinically significant changes from baseline in Urinalysis parameters
Tidsramme: 12 weeks
|
12 weeks
|
|
|
Part 1: Number of participants with clinically significant changes from baseline in Biochemistry parameters
Tidsramme: 12 weeks
|
12 weeks
|
|
|
Part 1: Number of participants with clinically significant changes from baseline in Vital signs
Tidsramme: 12 weeks
|
12 weeks
|
|
|
Part 1: Number of participants with clinically significant changes from baseline in physical examination
Tidsramme: 12 weeks
|
12 weeks
|
|
|
Part 1: Number of participants with clinically significant changes from baseline in ECG parameters
Tidsramme: 12 weeks
|
12 weeks
|
|
|
Part 1: Pre-dose plasma concentrations of Deucrictibant
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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"
Tidsramme: 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"
Tidsramme: Within 12 hours post-treatment
|
Within 12 hours post-treatment
|
|
|
Part 2: Time to End of Progression (EoP) in attack symptoms
Tidsramme: 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
Tidsramme: Up to 24 weeks
|
Up to 24 weeks
|
|
|
Part 2: Number of participants with clinically significant changes from baseline in Hematology parameters
Tidsramme: 24 weeks
|
24 weeks
|
|
|
Part 2: Number of participants with clinically significant changes from baseline in Urinalysis parameters
Tidsramme: 24 weeks
|
24 weeks
|
|
|
Part 2: Number of participants with clinically significant changes from baseline in Biochemistry parameters
Tidsramme: 24 weeks
|
24 weeks
|
|
|
Part 2: Number of participants with clinically significant changes from baseline in Vital signs
Tidsramme: 24 weeks
|
24 weeks
|
|
|
Part 2: Number of participants with clinically significant changes from baseline in physical examination
Tidsramme: 24 weeks
|
24 weeks
|
|
|
Part 2: Number of participants with clinically significant changes from baseline in ECG parameters
Tidsramme: 24 weeks
|
24 weeks
|
|
|
Part 2: Pharmacokinetics [PK]: Deucrictibant and deucrictibant metabolites plasma concentration-time profiles
Tidsramme: Day 1
|
Day 1
|
|
|
Part 3: Time to symptom relief, as PGI-C rating of at least "better"
Tidsramme: 12 hours post-treatment
|
12 hours post-treatment
|
|
|
Part 3: Time to symptom relief, as PGI-S rating of at least 1 point reduction
Tidsramme: 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"
Tidsramme: 24 hours post-treatment
|
24 hours post-treatment
|
Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Efterforskere
Efterforskere
- Studieleder: Study Director, Pharvaris, Pharvaris Netherlands B.V.
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Studiestart
Primær færdiggørelse (Anslået)
Primær færdiggørelse
Studieafslutning (Anslået)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Arvelige komplement-mangelsygdomme
- Primære immundefektsygdomme
- Karsygdomme
- Hjerte-kar-sygdomme
- Genetiske sygdomme, medfødte
- Sygdomme i immunsystemet
- Overfølsomhed, Øjeblikkelig
- Overfølsomhed
- Immunologiske mangelsyndromer
- Hudsygdomme
- Nældefeber
- Hudsygdomme, vaskulære
- Medfødte, arvelige og neonatale sygdomme og abnormiteter
- Hud- og bindevævssygdomme
- Angioødem
- Angioødem, arvelig
- Erhvervet angioødem
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- PHA022121-C308
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .