Clinical trial NCT05695950: A Study Evaluating the Effects of GLPG3667 Given as Oral Treatment for up to 24 Weeks in Adults With Dermatomyositis
Official title: A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered GLPG3667 Once Daily for 24 Weeks in Adult Subjects With Dermatomyositis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Dermatomyositis
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2023-01-25
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of orally administered GLPG3667 once daily for 24 weeks in adult participants with dermatomyositis (DM), followed by an open-label extension (OLE) period until Week 48.


Eligibility criteria: Key Inclusion Criteria:

* Participant has probable or definite DM in accordance with the ACR/EULAR criteria for at least 3 months.
* Participant with DM diagnosed in the 3 years prior to screening must have undergone cancer screening (according to local standard of care or applicable guidelines) within 1 year prior to screening. Note: The evidence of cancer screening must be documented.
* Participant must present objective evidence of active disease as defined by fulfilling 1 of the criteria below (as confirmed by the sponsor):

  * DM rash as defined by modified-Cutaneous Dermatomyositis Disease Area and Severity Index Activity Score (m-CDASI-A) ≥ 6 at screening, or
  * Creatine kinase (CK) \> 4x upper limit of normal (ULN) at screening, or
  * muscle biopsy evidence of active disease within 3 months prior to screening (defined as presence of active inflammation in muscle biopsy), or
  * muscle magnetic resonance imaging showing active inflammation (edema) of the proximal skeletal muscles within 3 months prior to screening, or
  * electromyography showing acute changes, such as spontaneous activity and myopathic changes not explained by other diseases within 3 months prior to screening, or
  * any other clinical evidence of active disease as confirmed by the steering committee.
* Participant has reduced muscle strength (defined as Manual Muscle Test-8 \< 142/150) and at least 2 additional abnormal core set measurements out of the following 5 at screening:

  * Physician's Global Disease Activity score \> 2/10 cm on the visual analog scale (VAS),
  * Patient's Global Disease Activity score \> 2/10 cm on VAS,
  * extra-muscular disease activity \> 2/10 cm on VAS,
  * Health Assessment Questionnaire-Disability Index score \> 0.25,
  * elevated muscle enzymes (e.g. aldolase, CK, ALT, AST, and lactate dehydrogenase) with at least 1 muscle enzyme \> 1.5x ULN.
* Participant previously demonstrated failure to or intolerance to first-line treatment (defined as oral corticosteroid\[s\] and at least 1 other immunosuppressant/ hydroxychloroquine) OR active disease despite treatment with first-line drugs. Currently, the participant is receiving maximum 3 treatments for DM (oral corticosteroid\[s\] and/or allowed immunosuppressant\[s\]/hydroxychloroquine) for at least 3 months and is on a stable dose (defined as no change in dose, type of administration, or dose regimen) for at least 4 weeks prior to screening and during screening within maximum allowed doses as specified in the study protocol. Note: Participants receiving 1 or no concomitant treatment for DM are also eligible.
* Open Label Extension : Participant must meet both of the following inclusion criteria at Visit 8 to be eligible for participation in the OLE period of the study: participant who may benefit from open-label treatment with GLPG3667, according to the investigator's judgment; participant who completed the 24-week double-blind treatment period on investigational product.

Key Exclusion Criteria:

* Participant has cancer-associated myositis (defined as myositis diagnosed within 2 years of cancer diagnosis with the exception of basal cell carcinoma, squamous cell carcinoma of the skin, or in situ uterine cervical carcinoma that has been excised and cured). Note: At least 1 year for basal cell carcinoma and squamous cell carcinoma or 5 years for in situ uterine cervical carcinoma must have passed since the excision.
* Participant has other causes of myositis (e.g. connective tissue disease) associated DM, polymyositis, juvenile DM, inclusion body myositis, or necrotizing idiopathic inflammatory myopathies (with or without rash) with the exception of overlap with secondary Sjogren's syndrome.
* Participant has permanent muscle weakness due to muscle damage (e.g. participant is wheelchair bound or has significant muscle atrophy on magnetic resonance imaging \[MRI\]) or a non-DM cause (drug-induced myopathy, including glucocorticoid-induced myopathy as primary cause of muscle weakness), according to investigator's judgement.
* Participant has taken any prohibited therapies within the defined washout periods before screening, and during screening as listed in the study protocol.
* Open Label Extension : Participant meeting one or more of the criteria at Visit 8 as defined in the protocol, cannot be selected for the OLE period of this clinical study. 1. Participant has total bilirubin \>1.5x ULN; however, participant with an isolated increase in total bilirubin \<3 x ULN due to Gilbert's Syndrome, with normal direct bilirubin, can be enrolled in the OLE period. 2. Participant has AST or ALT \>1.5 x ULN (hepatic injury), or AST or ALT \>=5 x ULN if judged to be of muscular origin (and confirmed by the steering committee) at Visit 7 and Visit 8.

Primary outcomes:
measure: Total improvement score [TIS] according to the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants With at Least Minimal Improvement According to the ACR/EULAR Criteria
timeFrame: Week 24
measure: Change From Baseline in Modified-Cutaneous DM Disease Area and Severity Index Activity Score (m-CDASI-A) at Week 24
timeFrame: Week 24
measure: Change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24
timeFrame: Week 24
measure: Change from baseline in the manual muscle test (MMT-8) at Week 24
timeFrame: Week 24
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation
timeFrame: Baseline (Day 1) up to Week 24
measure: Maximum Plasma Concentration (Cmax) of GLPG3667
timeFrame: Week 4
measure: Area Under the Plasma Concentration-Time Curve (AUC) of GLPG3667
timeFrame: Week 4
measure: Plasma Trough Concentration (Ctrough) at Steady State of GLPG3667
timeFrame: Week 2 predose until Week 24
Other outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and TEAEs Leading to Treatment Discontinuation
timeFrame: Baseline (Day 1) up to Week 52
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Neurology
state: Arizona
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials, Inc.
state: California
city: Kendall
country: United States
facility: New Access Research and Medical Center
state: Florida
city: Orlando
country: United States
facility: Omega Research Orlando, LLC
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Eagan
country: United States
facility: St. Paul Rheumatology
state: Minnesota
city: Lake Success
country: United States
facility: Northwell Health, LLC PRIME
state: New York
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research, P.C.
state: Pennsylvania
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Fundacion Respirar Consultorios Médicos Dr. Doreski
city: Cordoba
country: Argentina
facility: Hospital Cordoba
city: La Plata
country: Argentina
facility: Hospital Italiano de La Plata
city: La Plata
country: Argentina
facility: Framingham Centro Medico
city: Quilmes
country: Argentina
facility: Instituto Medico CER
city: Leuven
country: Belgium
facility: UZ Leuven
city: Santiago
country: Chile
facility: Enroll SpA
city: Santiago
country: Chile
facility: BioMedica Research Group Psicomedica Clinical and Research Group
city: Barranquilla
country: Colombia
facility: Clinica de la Costa S.A.S
city: Barranquilla
country: Colombia
facility: Centro de Investigacion Medico Asistencial S.A.S
city: Zipaquirá
country: Colombia
facility: Healthy Medical Center
city: Zagreb
country: Croatia
facility: Polyclinic Bonifarm
city: Zagreb
country: Croatia
facility: Solmed Polyclinic
city: Praha 2
country: Czechia
facility: Revmatologicky Ustav
city: Nice
country: France
facility: CHU de Nice Hôpital Pasteur 2 Centre de Réf des Maladies Neuromusculaires et SLA
city: Paris cedex 13
country: France
facility: Groupe Hospitalier Pitie-Salpetriere service de médecine interne et immunologie cliniqu
city: Strasbourg cedex
country: France
facility: CHU Strasbourg - Hôpital Hautepierre service de rhumatologie
city: Berlin
country: Germany
facility: Charité - Campus Charité Mitte - Klinik für Dermatologie, Venerologie und Allergologie
city: Gommern
country: Germany
facility: Helios Fachklinik Vogelsang-Gommern
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen - Universitäts-Hautklinik
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili) Medicina Interna
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico. PO San Marco
city: Milano
country: Italy
facility: Ospedale San Raffaele U.O. di Medicina Gen. Ind. Immunologico-Clinica
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana U.O. Reumatologia Universitaria
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas U.O. Reumatologia
city: Torino
country: Italy
facility: Ospedale San Giovanni Bosco
city: Mexico
country: Mexico
facility: Centro de Investigacion Clínica GRAMEL S.C
city: Mexico
country: Mexico
facility: Consultorio de Reumatologia Hospital Angeles Lindavista
city: Mérida
country: Mexico
facility: Medical Care & Research SA de CV
city: San Luis Potosi
country: Mexico
facility: Centro de Alta Especialidad en Reumatología e Investigación del Potosí S.C.
city: Bialystok
country: Poland
facility: Nova Reuma Domysławska i Rusiłowicz, Spółka Partnerska Lekarza Reumatologa i Fizjoterapeuty
city: Krakow
country: Poland
facility: Centrum Medyczne Plejady
city: Lublin
country: Poland
facility: Zespol Poradni Specjalistycznych Reumed
city: Warsawa
country: Poland
facility: Klinika Ambroziak ESTEDERM
city: Bucharest
country: Romania
facility: Spitalul Clinic 'Sf. Maria' Clinica de Medicina Interna si Reumatologie
city: Bucuresti
country: Romania
facility: Spitalul Clinic Colentina parent
city: Râmnicu Vâlcea
country: Romania
facility: Sc Medaudio-Optica SRL
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron Internal Medicine Dept.
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona Servicio de Medicina Interna
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge Servicio de Cardiologia
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Chertsey
country: United Kingdom
facility: St. Peter´s Hospital Dept of Rheumatology
city: Edinburgh
country: United Kingdom
facility: Western General Hospital Dept of Rheumatology
city: London
country: United Kingdom
facility: King's College Hospital Dept of Rheumatology
city: Salford
country: United Kingdom
facility: Salford Care Organisation Dept of Rheumatology
Study officials:
affiliation: Galapagos NV
name: Galapagos Study Director
role: STUDY_DIRECTOR
References: