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A Study Evaluating the Effects of GLPG3667 Given as Oral Treatment for up to 24 Weeks in Adults With Dermatomyositis

Phase 2
Recruiting
Conditions
Dermatomyositis
Interventions
Drug: GLPG3667
Drug: Placebo
Registration Number
NCT05695950
Lead Sponsor
Galapagos NV
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
62
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.

Key

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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
GLPG3667 During DB + During OLEGLPG3667Participants will receive GLPG3667 dose A orally once daily for 24 weeks in the double-blind (DB) treatment period. Eligible participants will roll-over to an open-label extension (OLE) period to receive the same dose for another 24 weeks.
Placebo During DB + GLPG3667 During OLEGLPG3667Participants will receive placebo matching to GLPG3667 orally once daily for 24 weeks in the DB treatment period. Eligible participants will roll-over to an OLE period to receive GLPG3667 dose A orally once daily for another 24 weeks.
Placebo During DB + GLPG3667 During OLEPlaceboParticipants will receive placebo matching to GLPG3667 orally once daily for 24 weeks in the DB treatment period. Eligible participants will roll-over to an OLE period to receive GLPG3667 dose A orally once daily for another 24 weeks.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With at Least Minimal Improvement at Week 24 According to the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) CriteriaWeek 24

Minimal improvement per ACR/EULAR was defined as total improvement score (TIS) of ≥ 20 points. The TIS is a score derived from the evaluation of the results from 6 core set measurements (CSMs) of myositis disease activity: Physician's Global Disease Activity Assessment; Patient's Global Disease Activity Assessment; Muscle Manual Test-8 (MMT-8); Health Assessment Questionnaire-Disability Index (HAQ-DI); Enzymes (aldolase, creatine kinase (CK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH); and Extra-muscular disease activity. The TIS is a scale from 0 to 100 that allows for the discrimination between minimal, moderate and major responders depending on their improvement in the combined 6 CSM.

Secondary Outcome Measures
NameTimeMethod
Change from baseline in the manual muscle test (MMT-8) at Week 24Week 24

MMT-8 is a set of 8 designated muscles, 7 of them being tested bilaterally (potential score 0-140). Axial (neck flexors) testing is included, so that potential maximum MMT-8 score = 150.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (SAEs), and TEAEs Leading to Treatment DiscontinuationBaseline (Day 1) up to Week 24
Change From Baseline in Modified-Cutaneous DM Disease Area and Severity Index Activity Score (m-CDASI-A) at Week 24Week 24

The CDASI is a clinician-scored single page instrument that separately measures activity (m-CDASI-A) and damage (m-CDASI-D) in the skin of DM participants. The m-CDASI-A consists of 3 activity measures (erythema, scale, and erosion/ulceration) assessed over 15 body areas along with the activity of Gottron's papules on hands and activity of periungual changes and alopecia. m-CDASI-A ranges from 0-100. Higher scores indicate more disease activity.

Change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24Week 24

The HAQ-DI is a generic rather than a disease-specific instrument, comprised of 8 sections: dressing, arising, eating, walking, hygiene, reach, grip, and activities. There are 2 or 3 questions for each section. Scoring within each section is from 0 \[without any difficulty\] to 3 \[unable to do\]. For each section the score given to that section is the worst score within the section. The 8 scores of the 8 sections are summed and divided by 8.

Maximum Plasma Concentration (Cmax) of GLPG3667Week 4
Area Under the Plasma Concentration-Time Curve (AUC) of GLPG3667Week 4
Plasma Trough Concentration (Ctrough) at Steady State of GLPG3667Week 2 predose until Week 24

Trial Locations

Locations (54)

Fundacion Cardiovascular de Colombia

🇨🇴

Floridablanca, Colombia

Fundacion Respirar Consultorios Médicos Dr. Doreski

🇦🇷

Ciudad Autonoma de Buenos Aires, Argentina

Clinica de la Costa S.A.S

🇨🇴

Barranquilla, Colombia

Charité - Campus Charité Mitte - Klinik für Dermatologie, Venerologie und Allergologie

🇩🇪

Berlin, Germany

HonorHealth Neurology

🇺🇸

Scottsdale, Arizona, United States

Inland Rheumatology Clinical Trials, Inc.

🇺🇸

Upland, California, United States

New Access Research and Medical Center

🇺🇸

Kendall, Florida, United States

Omega Research Orlando, LLC

🇺🇸

Orlando, Florida, United States

Augusta University

🇺🇸

Augusta, Georgia, United States

St. Paul Rheumatology

🇺🇸

Eagan, Minnesota, United States

Northwell Health, LLC PRIME

🇺🇸

Lake Success, New York, United States

Altoona Center for Clinical Research, P.C.

🇺🇸

Duncansville, Pennsylvania, United States

Arthritis & Osteoporosis Clinic

🇺🇸

Waco, Texas, United States

Hospital Cordoba

🇦🇷

Cordoba, Argentina

Hospital Italiano de La Plata

🇦🇷

La Plata, Argentina

Framingham Centro Medico

🇦🇷

La Plata, Argentina

UZ Leuven

🇧🇪

Leuven, Belgium

DCC Focus 5 - MEOH OOD

🇧🇬

Sofia, Bulgaria

Enroll SpA

🇨🇱

Santiago, Chile

BioMedica Research Group Psicomedica Clinical and Research Group

🇨🇱

Santiago, Chile

Healthy Medical Center

🇨🇴

Zipaquirá, Colombia

Clinical Research Chile SpA.

🇨🇱

Valdivia, Chile

Centro de Investigacion Medico Asistencial S.A.S

🇨🇴

Barranquilla, Colombia

Polyclinic Bonifarm

🇭🇷

Zagreb, Croatia

Solmed Polyclinic

🇭🇷

Zagreb, Croatia

Revmatologicky Ustav

🇨🇿

Praha 2, Czechia

CHU de Nice Hôpital Pasteur 2 Centre de Réf des Maladies Neuromusculaires et SLA

🇫🇷

Nice, France

Groupe Hospitalier Pitie-Salpetriere service de médecine interne et immunologie cliniqu

🇫🇷

Paris cedex 13, France

CHU Strasbourg - Hôpital Hautepierre service de rhumatologie

🇫🇷

Strasbourg cedex, France

Universitätsklinikum Tübingen - Universitäts-Hautklinik

🇩🇪

Tübingen, Germany

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (Presidio Spedali Civili) Medicina Interna

🇮🇹

Brescia, Italy

Azienda Ospedaliero Universitaria Policlinico. PO San Marco

🇮🇹

Catania, Italy

Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico

🇮🇹

Milano, Italy

Ospedale San Raffaele U.O. di Medicina Gen. Ind. Immunologico-Clinica

🇮🇹

Milano, Italy

Azienda Ospedaliero Universitaria Pisana U.O. Reumatologia Universitaria

🇮🇹

Pisa, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

🇮🇹

Roma, Italy

Istituto Clinico Humanitas U.O. Reumatologia

🇮🇹

Rozzano, Italy

Ospedale San Giovanni Bosco

🇮🇹

Torino, Italy

Consultorio de Reumatologia Hospital Angeles Lindavista

🇲🇽

Mexico, Mexico

Nova Reuma Domysławska i Rusiłowicz, Spółka Partnerska Lekarza Reumatologa i Fizjoterapeuty

🇵🇱

Bialystok, Poland

Centrum Medyczne Plejady

🇵🇱

Krakow, Poland

Zespol Poradni Specjalistycznych Reumed

🇵🇱

Lublin, Poland

Klinika Ambroziak ESTEDERM

🇵🇱

Warsawa, Poland

Spitalul Clinic 'Sf. Maria' Clinica de Medicina Interna si Reumatologie

🇷🇴

Bucharest, Romania

Spitalul Clinic Colentina parent

🇷🇴

Bucuresti, Romania

Sc Medaudio-Optica SRL

🇷🇴

Râmnicu Vâlcea, Romania

Hospital Universitari Vall d'Hebron Internal Medicine Dept.

🇪🇸

Barcelona, Spain

Hospital Clinic de Barcelona Servicio de Medicina Interna

🇪🇸

Barcelona, Spain

Hospital Universitari de Bellvitge Servicio de Cardiologia

🇪🇸

L'Hospitalet de Llobregat, Spain

Hospital Universitario Fundacion Jimenez Diaz

🇪🇸

Madrid, Spain

St. Peter´s Hospital Dept of Rheumatology

🇬🇧

Chertsey, United Kingdom

Western General Hospital Dept of Rheumatology

🇬🇧

Edinburgh, United Kingdom

King's College Hospital Dept of Rheumatology

🇬🇧

London, United Kingdom

Salford Care Organisation Dept of Rheumatology

🇬🇧

Salford, United Kingdom

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