A study evaluating the effects of GLPG3667 given as oral treatment for up to 24 weeks in adults with dermatomyositis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Galapagos

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

9 Aug 2023 → 20 Apr 2026

Decision date (initial)

2023-05-17

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Galapagos NV

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic, Safety, Pharmacokinetic, Others

To evaluate the efficacy of GLPG3667 compared to placebo on the signs and symptoms of dermatomyositis. Open Label Extension: to evaluate the safety and tolerability of GLPG3667 150 mg q.d. in subjects with DM.

Secondary objectives 3

1. To evaluate the efficacy of GLPG3667 150 mg once daily compared to placebo on signs and symptoms of dermatomyositis, skin disease activity in dermatomyositis, health-related outcomes (impact of dermatomyositis on activities in daily life of subjects with dermatomyositis), and muscle strength.
2. To evaluate the safety and tolerability of GLPG3667 in subjects with dermatomyositis.
3. To characterize the pharmacokinetics of GLPG3667 in subjects with dermatomyositis.

Conditions and MedDRA coding

dermatomyositis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Female or male subjects from 18 to 75 years of age inclusive, on the date of signing the informed consent form.
2. Subject has probable or definite DM in accordance with the ACR/EULAR criteria for at least 3 months.
3. Subject with dermatomyositis 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.
4. Subject must present objective evidence of active disease as defined by fulfilling 1 of the criteria below (as confirmed by the sponsor): dermatomyositis rash as defined by m-CDASI-A >= 6 at screening, or creatinine kinase > 4x ULN at screening, or muscle biopsy evidence of active disease within 3 months prior to screening (as 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.
5. Subject 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 and/or Patient’s Global Disease Activity score > 2/10 cm on the visual analog scale (VAS), and/or extra-muscular disease activity > 2/10 cm on VAS, and/or Health Assessment Questionnaire-Disability Index score > 0.25, and/or elevated muscle enzymes (e.g. aldolase, CK, ALT, AST, and lactate dehydrogenase) with at least 1 muscle enzyme > 1.5x ULN.
6. Subject previously demonstrated failure to or intolerance to first-line treatment (defined as oral corticosteroid[s] and at least 1 immunosuppressant/hydroxychloroquine) OR active disease despite treatment with first-line drugs. Currently, the subject is receiving maximum 3 treatments for dermatomyositis (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 protocol.
7. Open Label Extension : The ICF has been signed at the screening visit (see inclusion criteria #1 and #9). Subjects must meet both of the following inclusion criteria at Visit 8 to be eligible for participation in the OLE period of the study: subject who may benefit from open-label treatment with GLPG3667, according to the investigator’s judgment. Female or male subjects who completed the 24-week double-blind treatment period on IP.

Exclusion criteria 5

1. Subject 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).
2. Subject has other causes of myositis (e.g. connective tissue disease) associated dermatomyositis (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.
3. Subject has permanent muscle weakness due to muscle damage (e.g. subject is wheelchair bound or has significant muscle atrophy on MRI) or a non-DM cause (drug-induced myopathy, including glucocorticoid-induced myopathy as primary cause of muscle weakness), according to investigator’s judgement.
4. Subject has taken any prohibited therapies within the defined washout periods before screening, and during screening as listed in the protocol.
5. Open Label Extension : Subjects meeting one or more of the criteria at Visit 8 as defined in the protocool, cannot be selected for the OLE period of this clinical study. 1. Subject has total bilirubin >1.5x ULN; subjects 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. Subject 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Total improvement score [TIS] according to the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria at Week 24. Open Label Extension : Frequency and severity of TEAEs, treatment-emergent SAEs, and TEAEs leading to treatment discontinuation (over time up to Week 52).

Secondary endpoints 3

1. At week 24 - - Proportion of subjects with at least minimal improvement according to the ACR/EULAR criteria (defined as TIS of >= 20 points) at Week 24. - Change from baseline in modified-Cutaneous DM Disease Area and Severity Index Activity Score (m-CDASI-A). - Change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) - Change from baseline in the manual muscle test (MMT-8)
2. Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (SAEs), and TEAEs leading to treatment discontinuation (over time up to Week 24).
3. Estimated GLPG3667 maximum plasma concentration (Cmax), area under the plasma concentration-time curve (AUC), and trough plasma concentration (Ctrough) at steady-state.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Galapagos

Sponsor organisation

Galapagos

Address

Generaal De Wittelaan L11 A3

City

Mechelen

Postcode

2800

Country

Belgium

Scientific contact point

Organisation

Galapagos

Contact name

Galapagos Medical Information

Public contact point

Organisation

Galapagos

Contact name

Galapagos Medical Information

Third parties 5

Locations

10 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 138 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

21 submissions — initial application plus substantial / non-substantial modifications