Evaluation of the Efficacy and Safety of GLPG3667 in Adults with Active Systemic Lupus Erythematosus: A Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2023-503183-16-00
- Protocol
- GLPG3667-CL-215
- Sponsor
- Lakefront Biotherapeutics
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of GLPG3667 compared to placebo on disease activity in subjects with active **Systemic Lupus Erythematosus** (SLE). This is clinically relevant as it aims to determine the potential of GLPG3667 to reduce disease activity, which is a critical aspect of managing SLE and improving patient outcomes.
Secondary objectives include: - To further characterize the efficacy of GLPG3667 compared to placebo in subjects with active SLE. - To evaluate the safety and tolerability of GLPG3667 in subjects with active SLE. - To characterize the pharmacokinetics of GLPG3667 in subjects with active SLE.
Participants
The clinical trial involves a total of **126 participants** diagnosed with **Systemic Lupus Erythematosus** (SLE). The study population includes both female and male subjects aged between 18 and 75 years. Participants were selected based on a documented diagnosis of SLE as per the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria, with the disease diagnosed at least 24 weeks prior to the screening visit. The trial includes individuals with a total Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 6 or higher, and a clinical SLEDAI-2K score of 4 or higher at screening and baseline. Participants are required to have a positive result for antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA), or anti-Smith (anti-Sm) antibodies. The trial population is characterized by the presence of specific BILAG-based manifestations of SLE and requires stable background therapy with immunosuppressants or antimalarials for at least 12 weeks before screening. The study does not focus on any specific lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, ensuring comprehensive evaluation of the efficacy of GLPG3667 compared to placebo on disease activity in subjects with active SLE.
Plans and Procedures
The clinical trial is designed to evaluate the **efficacy**, safety, tolerability, pharmacokinetics, and pharmacodynamics of the orally administered investigational drug GLPG3667 in adult subjects with active **systemic lupus erythematosus** (SLE). This is a randomized, double-blind, placebo-controlled, multicenter study. Participants will be randomly assigned to receive either GLPG3667 or a placebo, which consists only of excipients identical to those in the active drug product. The trial is expected to commence recruitment on January 1, 2024, and conclude by March 31, 2026, with a maximum treatment period of 48 weeks.
The study will include several key visits: an initial screening visit, multiple follow-up visits, and an end-of-study visit. During the screening visit, eligibility will be assessed based on criteria such as age (18 to 75 years), a documented diagnosis of SLE, and specific disease activity scores. Follow-up visits will occur at regular intervals to monitor the participants' response to treatment and any adverse events. The primary endpoint is the proportion of subjects achieving the SLE Responder Index (SRI)-4 response at Week 32. Secondary endpoints include the SRI-4 response at Week 48, BILAG-based Composite Lupus Assessment (BICLA) response, and changes in joint counts and cutaneous lupus severity scores at Weeks 32 and 48.
Participants are expected to be involved in the study for the entire duration unless conditions arise that necessitate early termination, such as significant adverse events or withdrawal of consent. The trial will also assess treatment-emergent adverse events and pharmacokinetic parameters of GLPG3667. The study aims to provide comprehensive data on the potential of GLPG3667 as a therapeutic option for SLE, contributing to the understanding of its clinical benefits and safety profile.
Treatment
The clinical trial involves the administration of **GLPG3667**, an investigational medication, to evaluate its efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics in adult subjects with active **systemic lupus erythematosus** (SLE). **GLPG3667** is provided in the form of a capsule and is administered orally. The active substance in this medication is **GLPG3667 fumarate**, a chemical entity developed by GALAPAGOS. The maximum daily dose of **GLPG3667** is 150 mg, with a total maximum dose of 50.4 g over the course of the study. The treatment period extends up to 48 weeks, during which participant compliance will be monitored to ensure adherence to the dosing schedule.
The study also includes a **placebo** group to serve as a control for comparison with the active treatment. The placebo consists solely of excipients that are identical to those in the active **GLPG3667** drug product, ensuring that any observed effects can be attributed to the active substance rather than the formulation itself. The placebo is administered in the same pharmaceutical form and via the same route as the active medication, maintaining the double-blind nature of the trial. Participants will receive the placebo according to the same dosing schedule as those receiving **GLPG3667**, and compliance will be similarly monitored.
Efficacy
The efficacy of GLPG3667 in the treatment of active systemic lupus erythematosus (SLE) will be assessed through a randomized, double-blind, placebo-controlled, multicenter study. The primary endpoint for evaluating efficacy is the proportion of subjects achieving the Systemic Lupus Erythematosus Responder Index (SRI)-4 response at Week 32. Secondary endpoints include the proportion of subjects achieving the SRI-4 response at Week 48, the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) response at Weeks 32 and 48, and a ≥50% reduction in the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-A score at Weeks 32 and 48. Additionally, the proportion of subjects achieving the Lupus Low Disease Activity State (LLDAS) at Weeks 32 and 48 will be evaluated, along with changes from baseline in the 28-joint count for tender, swollen, and tender + swollen (active) joints at the same timepoints.
Data collection will involve validated scales and assessments, with efficacy parameters measured at specified intervals throughout the trial. The study will also monitor treatment-emergent adverse events (TEAEs), serious adverse events, and TEAEs leading to treatment discontinuation. Pharmacokinetic parameters, including the estimated maximum plasma concentration, area under the plasma concentration-time curve, and trough plasma concentration at steady-state for GLPG3667, will be analyzed to further understand the drug's efficacy and safety profile. The trial is designed to provide comprehensive data on the efficacy of GLPG3667 in managing disease activity in subjects with active SLE.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Female or male subjects from 18 to 75 years of age inclusive, on the date of signing the informed consent form (ICF).
- Subject with documented diagnosis of SLE as defined by the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria with a disease diagnosed >=24 weeks before the screening visit.
- Subject has a total Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score >=6 points and a clinical SLEDAI-2K score >=4 at screening and baseline (scores must be confirmed by central review at screening). Lupus headache, alopecia, organic brain syndrome, and mucous membrane ulceration will not count toward the score required for screening at entry. Clinical SLEDAI-2K excludes laboratory abnormalities such as hematuria, pyuria, urinary casts, proteinuria, positive anti-double-stranded deoxyribonucleic acid (antidsDNA), decreased complement, thrombocytopenia, and leukopenia.
- Subject is positive for 1 of the following: antinuclear antibodies (ANA) >=1:80 or positive anti-dsDNA (indeterminate values are considered positive), or positive anti-Smith (anti- Sm), as determined by the central laboratory.
- At least 1 of the following BILAG-based protocol-specific manifestations of SLE: (1) BILAG A or B score in the mucocutaneous body system; (2) BILAG A or B score in the musculoskeletal body system due to arthritis; (3) If only 1 B and no A score is present in the mucocutaneous body system or in the musculoskeletal body system due to arthritis, then at least 1 B score must be present in one of the other body systems, for a total of >=2 BILAG B body system scores.
- Background therapy with at least 1 of the following medications is required for >=12 weeks before the screening visit and must remain stable until randomization and throughout study participation: (1) 1 immunosuppressant (combination of immunosuppressants is not permitted), stable at least 8 weeks prior to screening; (2)1 antimalarial, stable at least 8 weeks prior to screening. In addition, oral CS (prednisone or equivalent) and/or NSAIDs background therapy is permitted but not required: (1) CS (prednisone or equivalent; <=30 mg/day; CS monotherapy is not permitted), stable at least 2 weeks prior to screening; AND/OR (2) Non-steroidal antiinflammatory drugs (NSAIDs; NSAIDs monotherapy is not permitted), stable at least 2 weeks prior to screening.
Exclusion Criteria
- Subject with active, severe lupus nephritis (World Health Organization Class III, IV) that requires or may require treatment with cytotoxic agents or high-dose corticosteroid are excluded. Subjects with pre-existing, controlled renal disease with serum creatinine <=2 x upper limit of normal (ULN) and either residual proteinuria up to 3 g/day or a urine protein: creatinine ratio (UPCR) of up to 3 mg/mg or 339 mg/mmol are allowed. Control of renal disease must be documented with at least 2 measurements of proteinuria or UPCR over the past 6 months.
- Subjects with a history of catastrophic antiphospholipid syndrome are excluded. This includes subjects with a serious thrombotic event (e.g. pulmonary embolism, stroke, deep vein thrombosis) or unexplained pregnancy loss within 1 year before the screening visit or history of 3 or more unexplained consecutive pregnancy losses. Subjects with antiphospholipid antibody syndrome on stable anticoagulant therapy at an effective dose are allowed.
- Subjects with active or unstable lupus neuropsychiatric manifestations, including but not limited to any condition defined by BILAG A criteria are excluded, with the exception of subjects with mononeuritis multiplex and polyneuropathy, who are allowed.
- Drug-induced systemic lupus erythematosus.
- Subject has a chronic hepatitis B virus (HBV) infection, as defined by positive HBV surface antigen (HBsAg) at screening and detectable HBV core antibody (HBcAb).
- Subject has chronic hepatitis C virus (HCV) infection, as defined by positive HCV antibody (Ab) at screening and detectable HCV viremia. Subjects with positive HCV Ab must undergo reflex HCV ribonucleic acid (RNA) testing, and subjects with HCV RNA positivity will be excluded. Subjects with positive HCV Ab and negative HCV RNA are eligible.
- Subject has a history of or a current immunosuppressive condition or a history of opportunistic infections (e.g. human immunodeficiency virus [HIV] infection, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis, herpes simplex, herpes zoster).
- Subject testing positive for severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) infection, even if fully vaccinated against SARS-CoV-2, as detected by rapid antigen testing and/or reverse transcription polymerase chain reaction (RT-PCR) test at screening and/or baseline (Day 1). Subject presenting any signs or symptoms suggestive of SARS-CoV-2 infection, as detected at screening or baseline following careful physical examination (e.g. cough, fever, headaches, fatigue, dyspnea, myalgia, anosmia, dysgeusia, anorexia, sore throat), should undergo testing even if fully vaccinated against SARS-CoV-2, as per locally applicable standard diagnostic criteria to diagnose SARS-CoV-2 infection, and excluded if positive.
- Subject meets 1 of the following tuberculosis (TB) criteria at screening: (1) A history of active or currently active TB (regardless of treatment). (2) A positive QuantiFERON®-TB Gold Plus In-tube test at screening unless the investigator assesses this is due to a documented history of adequately treated latent TB infection. Note: If the test result is indeterminate, it may be repeated once; if indeterminate or positive on retest, subject is not eligible.
- Subject with poorly controlled chronic cardiac, pulmonary, or renal disease.
- Subject has at screening, presence of severe renal impairment (defined as estimated glomerular filtration rate [eGFR] <30 mL/minute/1.73 m2, using the Chronic Kidney Disease Epidemiology equation).
- Prior exposure to tyrosine kinase 2 (TYK2) inhibitors.
- Female subject is pregnant or breast feeding or intending to become pregnant or breastfeed during the study.
- Subject has taken any prohibited therapies within the defined washout periods before screening, and during screening.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Bulgaria | Not Recruiting | 01 Jan 2024 | 7 |
 France | Not Recruiting | 01 Jan 2024 | 4 |
 Germany | Not Recruiting | 01 Jan 2024 | 7 |
 Hungary | Not Recruiting | 01 Jan 2024 | 6 |
 Poland | Not Recruiting | 01 Jan 2024 | 30 |
 Spain | Not Recruiting | 01 Jan 2024 | 16 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo consists only of excipients which are identical to those in the active GLPG3667 drug product | Placebo | N/A | — | — | — | N/A |
GLPG3667 | Test | CAPSULE | ORAL USE | 150 | 48 | PRD10211985 |