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

Trial ID: 2022-501097-19-00
Protocol: GLPG3667-CL-214
Sponsor: Lakefront Biotherapeutics

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Diseases & Conditions

Dermatomyositis

Objectives

The primary objective of this study is to evaluate the **efficacy** of GLPG3667 compared to placebo on the signs and symptoms of **dermatomyositis**. This is clinically relevant as dermatomyositis is a chronic inflammatory condition affecting the skin and muscles, and effective treatment options are essential for improving patient outcomes.

Secondary objectives include:

Evaluating the efficacy of GLPG3667 150 mg once daily compared to placebo on skin disease activity in dermatomyositis, health-related outcomes, and muscle strength.
Assessing the safety and tolerability of GLPG3667 in subjects with dermatomyositis.
Characterizing the pharmacokinetics of GLPG3667 in subjects with dermatomyositis.

Participants

The clinical trial involves a total of **28 participants** diagnosed with **dermatomyositis**, a condition characterized by muscle weakness and skin rash. The study population includes both **female and male subjects** aged between 18 to 75 years. Participants were selected based on their diagnosis of probable or definite dermatomyositis according to the ACR/EULAR criteria, with the condition present for at least three months. The trial includes individuals who have shown failure or intolerance to first-line treatments or have active disease despite such treatments. Participants are required to have objective evidence of active disease, such as a dermatomyositis rash or elevated creatinine kinase levels, and reduced muscle strength. The trial population is composed of individuals who are currently receiving a maximum of three treatments for dermatomyositis and are on a stable dose regimen. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, ensuring comprehensive evaluation of the treatment's efficacy and safety across a diverse group of subjects.

Plans and Procedures

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to assess the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of the investigational drug GLPG3667, administered orally once daily for 24 weeks in adult subjects diagnosed with **dermatomyositis**. The trial will involve a multi-center approach, ensuring a diverse participant pool. The study will include a placebo group to provide a control for comparison against the active treatment group receiving GLPG3667. The trial is expected to last until September 2025, with recruitment having commenced in May 2023.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age, diagnosis, and evidence of active disease. Following successful screening, participants will be randomized to receive either GLPG3667 or placebo. The primary endpoint is the proportion of subjects showing at least minimal improvement at Week 24 according to the ACR/EULAR criteria. Secondary endpoints include changes from baseline in disease activity scores and the frequency and severity of treatment-emergent adverse events (TEAEs).

Study visits will occur at regular intervals to monitor the participants' health, assess the drug's efficacy, and record any adverse events. The end-of-study visit will conclude the 24-week treatment period, with an option for eligible participants to enter an open-label extension phase to further evaluate the safety and tolerability of GLPG3667. The expected length of participant involvement is approximately 24 weeks, with conditions for early termination including significant adverse events or withdrawal of consent. Participants must adhere to the study protocol, including maintaining stable doses of any concurrent treatments for dermatomyositis, to remain in the trial.

Treatment

The clinical trial involves the administration of **GLPG3667**, an experimental medication, to evaluate its efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics in adult subjects with dermatomyositis. **GLPG3667** is provided in a **capsule** form and is administered orally. The active substance in the medication is **GLPG3667 fumarate**, a chemical compound. The dosage for the trial is set at 150 mg once daily, with a maximum treatment period of 24 weeks. The medication is manufactured by Galapagos and is not a pediatric formulation. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the protocol.

The study also includes a **placebo** as a comparator treatment to assess the efficacy of **GLPG3667**. The placebo is designed to mimic the experimental medication in appearance but does not contain any active substance. It is administered in the same **pharmaceutical form** and via the same **oral route** as **GLPG3667**. The use of a placebo allows for a double-blind, placebo-controlled study design, ensuring that neither the participants nor the investigators know which treatment is being administered, thereby reducing bias in the assessment of the treatment's effects.

Efficacy

The efficacy of GLPG3667 in the treatment of **dermatomyositis** will be assessed through a randomized, double-blind, placebo-controlled, multi-center study. The primary endpoint for evaluating efficacy is the proportion of subjects achieving at least minimal improvement at Week 24, as defined by the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria, with a total improvement score (TIS) of ≥ 20 points.

Secondary endpoints include changes from baseline at Week 24 in the modified-Cutaneous DM Disease Area and Severity Index Activity Score (m-CDASI-A), Health Assessment Questionnaire-Disability Index (HAQ-DI), and the manual muscle test (MMT-8). Additionally, the frequency and severity of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (SAEs), and TEAEs leading to treatment discontinuation will be monitored over time up to Week 24. Pharmacokinetic parameters such as the estimated maximum plasma concentration (Cmax), area under the plasma concentration-time curve (AUC), and trough plasma concentration (Ctrough) at steady-state will also be evaluated.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Female or male subjects from 18 to 75 years of age inclusive, on the date of signing the informed consent form.
Subject has probable or definite DM in accordance with the ACR/EULAR criteria for at least 3 months.
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.
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.
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.
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.
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.

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Exclusion Criteria

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).
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.
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.
Subject has taken any prohibited therapies within the defined washout periods before screening, and during screening as listed in the protocol.
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.

Trial Status by Country

Country	Status	Start of Recruitment	Planned Patients
Belgium	Not Recruiting	30 May 2023	3
Bulgaria	Not Recruiting	30 May 2023	3
Croatia	Not Recruiting	30 May 2023	3
Czechia	Not Recruiting	30 May 2023	2
France	Not Recruiting	30 May 2023	2
Germany	Not Recruiting	30 May 2023	2
Italy	Not Recruiting	30 May 2023	6
Poland	Not Recruiting	30 May 2023	4
Romania	Not Recruiting	30 May 2023	5
Spain	Not Recruiting	30 May 2023	2