Clinical trial • Phase III • Immunology|Dermatology

4-[3-(CYANOMETHYL)-3-(3',5'-DIMETHYL-1H,1'H-[4,4'-BIPYRAZOL]-1-YL)AZETIDIN-1-YL]-2,5-DIFLUORO-N-[(2S)-1,1,1-TRIFLUOROPROPAN-2-YL]BENZAMIDE for Prurigo nodularis

Phase III trial of 4-[3-(CYANOMETHYL)-3-(3',5'-DIMETHYL-1H,1'H-[4,4'-BIPYRAZOL]-1-YL)AZETIDIN-1-YL]-2,5-DIFLUORO-N-[(2S)-1,1,1-TRIFLUOROPROPAN-2-YL]BENZAM…

Overview

Trial Therapeutic Area
Immunology|Dermatology
Trial Disease
Prurigo nodularis
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
07-08-2024
First CTIS Authorization Date
03-12-2024

Trial design

Randomised, placebo (placebo to povorcitinib) qd for 24 weeks (placebo arm is described as 'placebo qd for 24 weeks').-controlled Phase III trial in Poland, Spain, Germany and others.

Randomised
Yes
Comparator
Placebo (Placebo to Povorcitinib) QD for 24 weeks (placebo arm is described as 'Placebo QD for 24 weeks').
Target Sample Size
330
Trial Duration For Participant
336

Eligibility

Recruits 330 Vulnerable populations are addressed: participants must have the ability to comprehend and willingness to sign a written ICF. The trial metadata flags vulnerable populations selected and the protocol explicitly excludes, for France only, "vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection or who are unable to express their consent per article L.1121-8 of the French Public Health Code, not affiliated to a social security per article L.1121-8-1 of the French Public Health Code." Consent must be provided in written ICF; no paediatric/assent procedures are described (trial enrols 18–75 years)..

Pregnancy Exclusion
5. Pregnant (or are considering pregnancy) or breastfeeding.
Vulnerable Population
Vulnerable populations are addressed: participants must have the ability to comprehend and willingness to sign a written ICF. The trial metadata flags vulnerable populations selected and the protocol explicitly excludes, for France only, "vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection or who are unable to express their consent per article L.1121-8 of the French Public Health Code, not affiliated to a social security per article L.1121-8-1 of the French Public Health Code." Consent must be provided in written ICF; no paediatric/assent procedures are described (trial enrols 18–75 years).

Inclusion criteria

  • {"criterion_text":"- Ability to comprehend and willingness to sign a written ICF for the study.\n- 18 to 75 years of age.\n- Clinical diagnosis of PN for at least 3 months before screening.\n- Pruritus, defined as an average Itch NRS score ≥ 7 during the 7 days prior to Day 1.\n- ≥ 20 pruriginous lesions in total on ≥ 2 different body regions (both legs, and/or both arms, and/or trunk) at screening and Day 1.\n- IGA-CPG-S score ≥ 3 at screening and Day 1.\n- Documented history of treatment failure, demonstrated intolerance, or contraindication to a previous PN treatment (eg, TCS or TCI) with the exception of treatment failure with prior topical or systemic JAK or TYK2 inhibitors (see Exclusion Criterion 10).\n- Willingness to avoid pregnancy or fathering children based on the criteria detailed in section 5.1. of the protocol (under inclusion criteria 8).\n- Willing and able to comply with the study protocol and procedures."}

Exclusion criteria

  • {"criterion_text":"- 1. Chronic pruritus due to a condition other than PN.\n- 19. Known hypersensitivity or severe reaction to povorcitinib or excipients of povorcitinib (refer to the IB) and/or other products in the same class.\n- 20. Any condition, laboratory result, or result of screening assessments that would, in the investigator's and sponsor's (or designee's) judgment, interfere with full participation in the study, including administration of study drug and attending required study visits, pose a significant risk to the participant, or interfere with interpretation of study data.\n- 2. Neuropathic and psychogenic pruritus.\n- 21. The following participants are excluded in France: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection or who are unable to express their consent per article L.1121-8 of the French Public Health Code, not affiliated to a social security per article L.1121-8-1 of the French Public Health Code.\n- 3. Diagnosis of PN secondary to medications.\n- 4. Active AD lesions within 3 months of screening.\n- 5. Pregnant (or are considering pregnancy) or breastfeeding.\n- 6. Concurrent conditions or history of other diseases detailed in section 5.2. of the protocol (under exclusion criteria 6).\n- 7. A screening 12-lead ECG that demonstrates clinically significant abnormalities requiring treatment (eg, acute myocardial infarction, serious tachyarrhythmias or bradyarrhythmias) or that is indicative of serious underlying heart disease (eg, cardiomyopathy, major congenital heart disease, low voltage in all leads, Wolff Parkinson-White syndrome) or criteria associated with QT/QTcF abnormalities.\n- 8. Significant trauma or major surgery (per investigator's assessment) within 30 days prior to screening.\n- 10. History of treatment failure for PN or any other inflammatory condition.\n- 9. Planned or expected major surgery during the initial 24 weeks of treatment with study drug (ie, during the PC period of the study).\n- 13. Receipt of medical treatment or investigational drugs within intervals specified in section 5.2 of the protocol (under exclusion criteria 13)\n- 11. History of clinically significant (per investigator's judgment) drug or alcohol abuse within 6 months prior to screening.\n- 12. Initiation or changing the dose of any of the treatments listed in section 5.2. of the protocol (under exclusion criteria 12) within 3 months of Day 1 or expected dose change of any of the following treatments during the initial 24 weeks of treatment with study drug (ie, during the PC period).\n- 14. Concurrent enrollment in another clinical study.\n- 15. At the screening visit, any of the laboratory abnormalities defined in Table 6 of the protocol.\n- 16. Evidence of infection with Mycobacterium tuberculosis (ie, TB) as defined in Section 8.3.5.2.\n- 17. Active HIV or acquired immunodeficiency syndrome. Active HIV is defined as a confirmed positive anti-HIV antibody test (see Section 8.3.5.3).\n- 18. Evidence of HBV or HCV infection or risk of reactivation (see Section 8.3.5.4)."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Proportion of participants achieving Itch NRS4 (≥ 4-point improvement [reduction] in Itch NRS score from baseline) and IGA-CPG-S-TS (IGA CPG-S score of 0 or 1 with a ≥ 2-grade improvement from baseline) at Week 24","definition_or_measurement_approach":"Itch NRS4 defined as ≥4-point improvement (reduction) in Itch NRS score from baseline; IGA-CPG-S-TS defined as IGA CPG-S score of 0 or 1 with a ≥2-grade improvement from baseline; assessed at Week 24."}

Secondary endpoints

  • {"endpoint_text":"- Proportion of participants achieving Itch NRS4 at Week 24","definition_or_measurement_approach":"Itch NRS4 = ≥4-point improvement in Itch NRS score from baseline; assessed at Week 24."}
  • {"endpoint_text":"- Proportion of participants achieving IGA CPG S-TS at Week 24","definition_or_measurement_approach":"IGA-CPG-S-TS = IGA CPG-S score of 0 or 1 with a ≥2-grade improvement from baseline; assessed at Week 24."}
  • {"endpoint_text":"- Proportion of participants achieving Itch NRS4 at Week 4","definition_or_measurement_approach":"Itch NRS4 = ≥4-point improvement in Itch NRS score from baseline; assessed at Week 4."}

Recruitment

Registry Or Advocacy Recruitment
True, Magdeburger Company For Medical Studies & Services GmbH (listed as a Patient organisation/association) is named.
Digital Remote Recruitment
True, the trial uses digital/remote methods including online pre-screeners, patient websites, online banner ads, Facebook adverts, SMS recruitment texts, online landing pages, and remote eCOA (Signant Health eCOA).
Planned Sample Size
330
Recruitment Window Months
33
Consent Approach
Written informed consent (ICF) required: participants must be able to comprehend and sign a written ICF. Consent documents (L1_SIS-ICF_Main and related documents) are provided in multiple language versions (English, German, French, Dutch and country-specific translations) and country-specific participant information/ICF documents are available. Trial enrols adults (18–75) so consent is provided by the participant; no paediatric assent described.

Methods

  • Online banner ads and digital advertising (documents: K1_PN_Banner_Ads, K2_PN_BannerAds, facebook_feed/facebook_stories) targeting potential patients via web and social media.
  • Patient-facing study website / landing page (K2_PN_Patient Website, K2_Galen_Patient_Website) providing study information and contact details in multiple languages.
  • Online pre-screener (K2_Online PreScreener / PN Online PreScreener) to assess eligibility remotely prior to site contact.
  • SMS recruitment messages (K2_SIGAL SMS recruitment text) to potential participants.
  • Concierge service and participant support (L2_Concierge scripts, reminder cards, emails and text messages) to support enrolment and retention.
  • Recruitment via specialist patient recruitment agency (Galen Patient Recruitment Inc.) and other recruitment vendors listed (e.g., Medical Equipment Supplies And Management Limited providing study supplies).
  • Country-specific contact/location lists and materials in local languages (K2_Contact_Locat_en/nl/fr and language-specific patient materials) to direct potential participants to local sites.

Geography

Total Number Of Sites
47
Total Number Of Participants
170

Poland

Earliest CTIS Part Ii Submission Date
30-10-2024
Latest Decision Or Authorization Date
13-03-2026
Processing Time Days
499
Number Of Sites
12
Number Of Participants
45

Sites

Site Name
Uniwersytecki Szpital Kliniczny Im.Fryderyka Chopina W Rzeszowie
Department Name
Klinika Dermatologii
Contact Person Name
Adam Reich
Contact Person Email
adamandrzejreich@gmail.com
Site Name
Medicover Integrated Clinical Services Sp. z o.o.
Department Name
MICS Centrum Medyczne Toruń
Contact Person Name
Aleksandra Badzian
Contact Person Email
a.badzian@naszlekarz.pl
Site Name
Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych I Administracji
Department Name
Klinika Dermatologii
Contact Person Name
Irena Walecka-Herniczek
Contact Person Email
irena.walecka@cskmswia.gov.pl
Site Name
Cityclinic Przychodnia Lekarsko-Psychologiczna Matusiak sp.p.
Contact Person Name
Jacek Szepietowski
Contact Person Email
cityclinic.matusiak@gmail.com
Site Name
Santa Sp. z o.o.
Department Name
Santa Familia PTG Łódź
Contact Person Name
Cezary Chwała
Contact Person Email
cezary.chwala@ptg-network.com
Site Name
Dermoklinika-Centrum Medyczne" Spółka Cywilna M.Kierstan, J.Narbutt, A.Lesiak
Contact Person Name
Joanna Narbutt
Site Name
LUXDERM Specjalistyczny Gabinet Dermatologiczny Prof. Dr. Hab. N. Med. Dorota Krasowska
Contact Person Name
Dorota Krasowska
Contact Person Email
gabinetluxderm@gmail.com
Site Name
Clinical Research Center Sp. z o.o. Medic-R sp.k.
Contact Person Name
Magdalena Czarnecka-Operacz
Contact Person Email
biuro@cr-center.pl
Site Name
"HIGH-MED" Przychodnia Specjalistyczna, Poradnia dermatologiczna
Contact Person Name
Dorota Bystrzanowska
Site Name
Akk Medical Sp. z o.o.
Department Name
Centrum Medyczne Tu Się Leczy
Contact Person Name
Izabela Karamon
Contact Person Email
rejestracja@tusieleczy.pl
Site Name
Care Clinic Sp. z o.o.
Department Name
Care Clinic Centrum Medyczne
Contact Person Name
Dominika Wcisło-Dziadecka
Contact Person Email
poczta@careclinic.katowice.pl
Site Name
Royalderm Agnieszka Nawrocka
Contact Person Name
Witold Owczarek
Contact Person Email
witold.owczarek@dermedicus.pl

Spain

Earliest CTIS Part Ii Submission Date
19-09-2024
Latest Decision Or Authorization Date
05-02-2026
Processing Time Days
504
Number Of Sites
13
Number Of Participants
22

Sites

Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Dermatology
Contact Person Name
Jose Juan Pereyra Rodriguez
Contact Person Email
jpereyra@us.es
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Dermatology
Contact Person Name
Rafael Botella Estrada
Contact Person Email
botella_rafest@gva.es
Site Name
Hospital Universitario Clinico San Cecilio
Department Name
Dermatology
Contact Person Name
Francisco Jose Navarro Triviño
Contact Person Email
fntmed@gmail.com
Site Name
Hospital Universitario Reina Sofia
Department Name
Dermatology
Contact Person Name
Juan Alberto Ruano Ruiz
Contact Person Email
juanruanoruiz@mac.com
Site Name
Hospital Universitario Puerta De Hierro De Majadahonda
Department Name
Dermatology
Contact Person Name
Angel Rosell Diaz
Site Name
Complexo Hospitalario Universitario De Santiago
Department Name
Dermatology
Contact Person Name
Maria Angeles Florez Menendez
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Dermatology
Contact Person Name
Maria Bibiana Perez Garcia
Contact Person Email
bibianapg1@gmail.com
Site Name
Hospital Universitario 12 De Octubre
Department Name
Dermatology
Contact Person Name
Fátima Tous Romero
Contact Person Email
Fatima.tous@salud.madrid.org
Site Name
Hospital De Manises
Department Name
Dermatology
Contact Person Name
Antonio Martorell Calatayud
Contact Person Email
martorell_antcal@gva.es
Site Name
Hospital Germans Trias I Pujol
Department Name
Dermatology
Contact Person Name
Monica Munera Campos
Contact Person Email
muneracampos@gmail.com
Site Name
Hospital De La Santa Creu I Sant Pau
Department Name
Dermatology
Contact Person Name
Esther Serra-Baldrich
Contact Person Email
eserra@santpau.cat
Site Name
Hospital Universitario La Paz
Department Name
Dermatology
Contact Person Name
Pedro Francisco Herranz Pinto
Contact Person Email
pedro.herranz@salud.madrid.org
Site Name
Hospital General Universitario Dr. Balmis
Department Name
Dermatology
Contact Person Name
Juan Francisco Silvestre Salvador
Contact Person Email
silvestre_jfr@gva.es

Germany

Earliest CTIS Part Ii Submission Date
19-09-2024
Latest Decision Or Authorization Date
29-12-2025
Processing Time Days
466
Number Of Sites
14
Number Of Participants
42

Sites

Site Name
Klinikum Oldenburg AöR
Department Name
Universitätsklinik für Dermatologie und Allergologie
Contact Person Name
Nikolaos PATSINAKIDIS
Site Name
Deutsches Rotes Kreuz Gemeinnuetzige Krankenhaus Sachsen GmbH
Department Name
Dermatology
Contact Person Name
Martin KAATZ
Contact Person Email
kaatz.martin@drk-khs.de
Site Name
Klinikum Darmstadt GmbH
Department Name
Dermatology
Contact Person Name
Mana zur Bruegge
Site Name
Goethe University Frankfurt
Department Name
Klinik für Dermatologie, Venerologie und Allergologie (KDVA), Klinische Forschung
Contact Person Name
Andreas PINTER
Contact Person Email
pinter-klifo-ffm@gmx.de
Site Name
Elbe Kliniken Stade-Buxtehude Elbe Klinikum Buxtehude gGmbH
Department Name
Klinik für Dermatologie
Contact Person Name
Andreas KLEINHEINZ
Site Name
Rosenpark Research GmbH
Department Name
Dermatology
Contact Person Name
Oliver WEIRICH
Site Name
Technische Universitaet Dresden
Department Name
Department of Dermatology
Contact Person Name
Roland ASCHOFF
Contact Person Email
roland.aschoff@ukdd.de
Site Name
Universitaetsklinikum Aachen AöR
Department Name
Klinik für Dermatologie und Allergologie - Hautklinik
Contact Person Name
Amir YAZDI
Contact Person Email
ayazdi@ukaachen.de
Site Name
Universitaetsklinikum Muenster AöR
Department Name
Dermatology
Contact Person Name
Sonja STÄNDER
Contact Person Email
sonja.staender@uni-muenster.de
Site Name
Hautarztpraxis Dr Med Matthias Hoffmann
Contact Person Name
Matthias HOFFMANN
Contact Person Email
drho@hautarzt-dr-hoffmann.de
Site Name
Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)
Department Name
Dermatologie und Allergologie
Contact Person Name
Alexander ZINK
Contact Person Email
alexander.zink@tum.de
Site Name
BAG Dres. med. Quist PartG
Contact Person Name
Sven QUIST
Contact Person Email
studie@dermatologie-quist.de
Site Name
Magdeburger Company For Medical Studies & Services GmbH
Contact Person Name
Jens-Joachim BRÜCHER
Contact Person Email
bruecher@dermacare.md
Site Name
Universitaetsmedizin Goettingen
Department Name
Department Dermatology, Venerology, Allergology
Contact Person Name
Timo BUHL

Belgium

Earliest CTIS Part Ii Submission Date
31-10-2024
Latest Decision Or Authorization Date
31-03-2026
Processing Time Days
516
Number Of Sites
5
Number Of Participants
16

Sites

Site Name
Centre hospitalier universitaire de Liege
Department Name
Dermatology
Contact Person Name
Arjen Nikkels
Contact Person Email
af.nikkels@chuliege.be
Site Name
Universitair Ziekenhuis Gent
Department Name
Dermatology
Contact Person Name
Reinhart Speeckaert
Contact Person Email
reinhart.speeckaert@uzgent.be
Site Name
Grand Hopital De Charleroi
Department Name
Dermatology
Contact Person Name
Pierre-Paul Roquet-Gravy
Site Name
Cliniques Universitaires Saint-Luc
Department Name
Dermatology
Contact Person Name
Pierre-Dominique Ghislain
Site Name
Az St-Jan Brugge-Oostende A.V.
Department Name
Dermatology
Contact Person Name
Els Wittouck
Contact Person Email
Els.wittouck@azsintjan.be

Czechia

Earliest CTIS Part Ii Submission Date
23-08-2024
Latest Decision Or Authorization Date
09-04-2026
Processing Time Days
594
Number Of Sites
3
Number Of Participants
45

Sites

Site Name
Kozni ambulance
Contact Person Name
Petr Arenberger
Contact Person Email
avemedica@email.cz
Site Name
Clintrial s.r.o.
Contact Person Name
Otakar Komárek
Contact Person Email
o.komarek@clintrial.cz
Site Name
Sanixtra CZ s.r.o.
Department Name
Poliklinika Hůrka
Contact Person Name
Lucia Mansfeldová
Contact Person Email
lucia.mansfeldova@sanixtra.eu

Sponsor

Primary sponsor

Full Name
Incyte Corp.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Icon Clinical Research Limited
Responsibilities
Multiple operational roles including codes [1,12,13,15 (concierge service),2,4,5,6] as listed in sponsorDuties
Name
IQVIA Limited
Responsibilities
Cardiovascular events adjudication
Name
Suvoda LLC
Responsibilities
Operational role (sponsorDuties code 3) - contact email green@suvoda.com

Third parties

  • {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties codes: [3]","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Incyte Corp.","duties_or_roles":"sponsorDuties codes: [15] (value: 'Serum Biomarker and PK')","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Galen Patient Recruitment Inc.","duties_or_roles":"sponsorDuties codes: [15] (value: 'Recruitment activities')","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties codes: [1,12,13,15 (value: 'Concierge service'),2,4,5,6]","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"sponsorDuties codes: [15] (value: 'Cardiovascular events adjudication')","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Medical Equipment Supplies And Management Limited","duties_or_roles":"sponsorDuties codes: [15] (value: 'Study supplies like wood lamps, incubators, freezers')","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Signant Health Management Limited","duties_or_roles":"sponsorDuties codes: [15] (value: 'eCOA')","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"sponsorDuties codes: [15] (value: 'packaging, labeling and batch release')","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Veeva Systems Inc.","duties_or_roles":"sponsorDuties codes: [7]","organisation_type":"Non-Pharmaceutical company"}

Investigational products

Investigational Product Name
Povorcitinib
Active Substance
4-[3-(CYANOMETHYL)-3-(3',5'-DIMETHYL-1H,1'H-[4,4'-BIPYRAZOL]-1-YL)AZETIDIN-1-YL]-2,5-DIFLUORO-N-[(2S)-1,1,1-TRIFLUOROPROPAN-2-YL]BENZAMIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
MIA Number(s): DE_BW_01_MIA_2022_0034; IMP12181/00001; MIA Number: 7007F
Frequency
Once daily (QD) (study arms: Dose 1 QD or Dose 2 QD for 24 weeks)
Investigational Product Name
Placebo to Povorcitinib
Modality
Other
Authorisation Status
MIA Number: DE_BW_01_MIA_2022_0034 (used as placebo comparator in trial)
Frequency
QD (placebo matched to active dosing schedule)

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