A Study Evaluating the Effects of GLPG3667 Administered as Oral Treatment in Adult Participants With Active Systemic Lupus Erythematosus

Phase 2

Active, not recruiting

• Conditions: Systemic Lupus Erythematosus
• Interventions: Drug: GLPG3667; Drug: Placebo

• Registration Number: NCT05856448
• Lead Sponsor: Galapagos NV

Brief Summary

A study evaluating the efficacy, safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GLPG3667 administered orally once daily for 48 weeks in approximately 180 adult participants with active Systemic Lupus Erythematosus (SLE).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-05-03
• Study First Submitted QC: 2023-05-04
• Study First Posted: 2023-05-12
• Study Start: 2023-06-28
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-12
• Last Update Posted: 2025-03-14
• Primary Completion: 2025-10
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 186

Inclusion Criteria

1. Participant 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.

2. Participant 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 (anti-dsDNA), decreased complement, thrombocytopenia, and leukopenia.

3. Participant 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.

4. At least 1 of the following BILAG-based protocol-specific manifestations of SLE:

   • BILAG A or B score in the mucocutaneous body system.
   • BILAG A or B score in the musculoskeletal body system due to arthritis.
   • 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.

5. 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 immunosuppressant (combination of immunosuppressants is not permitted), stable at least 8 weeks prior to screening.
   • 1 antimalarial, stable at least 8 weeks prior to screening. In addition, oral corticosteroids (CS) (prednisone or equivalent) and/or NSAIDs background therapy is permitted but not required:
   • CS (prednisone or equivalent; <=30 mg/day; CS monotherapy is not permitted), stable at least 2 weeks prior to screening; AND/OR
   • Non-steroidal anti-inflammatory drugs (NSAIDs; NSAIDs monotherapy is not permitted), stable at least 2 weeks prior to screening.

Key

Exclusion Criteria

1. Participant with active, severe lupus nephritis (World Health Organization Class III, IV) that requires or may require treatment with cytotoxic agents or high-dose CS are excluded.

2. Participants with pre-existing, controlled renal disease with serum creatinine≥ 2 x upper limit of normal (ULN) and either residual proteinuria up to 3 grams/day (g/day) or a urine protein: creatinine ratio (UPCR) of up to 3 milligrams/milligrams (mg/mg) or 339 milligrams of albumin per millimole of creatinine (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.

3. Participants with a history of catastrophic antiphospholipid syndrome are excluded. This includes Participants 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. Participants with antiphospholipid antibody syndrome on stable anticoagulant therapy at an effective dose are allowed.

4. Participants 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 participants with mononeuritis multiplex and polyneuropathy, who are allowed.

5. Drug-induced SLE.

6. Participant has a chronic hepatitis B virus (HBV) infection, as defined by positive HBV surface antigen (HBsAg) at screening and detectable HBV core antibody (HBcAb).

7. Participant has chronic hepatitis C virus (HCV) infection, as defined by positive HCV antibody (Ab) at screening and detectable HCV viremia. Participants with positive HCV Ab must undergo reflex HCV ribonucleic acid (RNA) testing, and Participants with HCV RNA positivity will be excluded. Participants with positive HCV Ab and negative HCV RNA are eligible.

8. Participant 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).

9. Participant 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 revert transcription polymerase chain reaction (RT-PCR), test at screening and/or baseline (Day 1). Participant 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, dyspnoea, 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.

10. Participant meets 1 of the following tuberculosis (TB) criteria at screening:

    • A history of active or currently active TB (regardless of treatment).
    • 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, Participant is not eligible.

11. Participant with poorly controlled chronic cardiac, pulmonary, or renal disease.

12. Participant 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).

13. Prior exposure to tyrosine kinase 2 (TYK2) inhibitors.

14. Female participant is pregnant or breast feeding or intending to become pregnant or breastfeed during the study.

15. Participant has taken any prohibited therapies within the defined washout periods before screening, and during screening.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
GLPG3667 - Treatment A	GLPG3667	Participant will receive a dose A of GLPG3667 capsules orally once daily (q.d.) for 48 weeks.
GLPG3667 - Treatment B	GLPG3667	Participant will receive a dose B of GLPG3667 capsules orally (q.d.) for 48 weeks.
Placebo	Placebo	Participant will receive placebo matched to GLPG3667 capsules orally q.d for 48 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants who Achieved the SLE Responder Index (SRI)-4 Response at Week 32	Week 32

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants who Achieved the SRI-4 Response at Week 48	Week 48
Percentage of Participants who Achieved the British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response at Week 32 and Week 48	Week 32, Week 48
Percentage of Participants with >=50% Reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score at Week 32 and Week 48	Week 32, Week 48
Percentage of Participants who achieve Lupus Low Disease Activity State (LLDAS) at Week 32 and Week 48	Week 32, Week 48
Change from Baseline in the 28-joint Count for Tender joints at Week 32 and Week 48	Baseline, Week 32 and Week 48
Change from Baseline in the 28-joint Count for Swollen joints at Week 32 and Week 48	Baseline, Week 32 and Week 48
Change from Baseline in the 28-joint Count for Tender + Swollen (active) joints at Week 32 and Week 48	Baseline, Week 32 and Week 48
Number of Participants with Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs leading to treatment discontinuation	From the start of first dose till 30 days after the last dose (up to 52 weeks)
Pharmacokinetics (PK) of GLPG3667: Estimated Maximum Plasma Concentration (Cmax)	Predose every 4 weeks from Week 2 to Week 32 and 0.5hours (h)-2h , 2h-4h , 4h-6h postdose at Week 4, Predose every 8 weeks from Week 32 to Week 48
PK of GLPG3667: Estimated Area Under the Concentration Time Curve (AUC) at Steady State	Predose every 4 weeks from Week 2 to Week 32 and 0.5-2h , 2h-4h , 4h-6h postdose at Week 4, Predose every 8 weeks from Week 32 to Week 48
PK of GLPG3667: Estimated Trough Concentration (Ctrough) at Steady State	Predose every 4 weeks from Week 2 to Week 32 and 0.5-2h , 2h-4h , 4h-6h postdose at Week 4, Predose every 8 weeks from Week 32 to Week 48

Trial Locations

Locations (84)

Desert Medical Advances; 🇺🇸 Rancho Mirage, California, United States

Millennium Clinical Trials; 🇺🇸 Simi Valley, California, United States

Inland Rheumatology Clinical Trials; 🇺🇸 Upland, California, United States

Upland Rheumatology Center; 🇺🇸 Upland, California, United States

Arthritis & Rheumatic Disease Specialties; 🇺🇸 Aventura, Florida, United States

Omega Research DeBary; 🇺🇸 DeBary, Florida, United States

Alloy Clinical Research, LLC; 🇺🇸 Kissimmee, Florida, United States

San Marcus Research Clinic; 🇺🇸 Miami, Florida, United States

Advanced Pharma - Miami; 🇺🇸 Miami, Florida, United States

Professional Research Center; 🇺🇸 Miami, Florida, United States

Integral Rheumatology & Immunology Specialists; 🇺🇸 Plantation, Florida, United States

Alliance Clinical Research of Tampa; 🇺🇸 Tampa, Florida, United States

Albuquerque Clinical Trials; 🇺🇸 Albuquerque, New Mexico, United States

DJL Clinical Research; 🇺🇸 Charlotte, North Carolina, United States

Lynn Institute of Tulsa; 🇺🇸 Tulsa, Oklahoma, United States

New Phase Research & Development; 🇺🇸 Knoxville, Tennessee, United States

Hospital Universitario de Badajoz; 🇪🇸 Badajoz, Spain

GCM Medical Group; 🇵🇷 San Juan, Puerto Rico

University of Arizona College of Medicine - Tucson; 🇺🇸 Tucson, Arizona, United States

University of California San Diego; 🇺🇸 La Jolla, California, United States

Office of Ramesh C. Gupta MD / Shelby Research LLC - Tennessee; 🇺🇸 Memphis, Tennessee, United States

Care and Cure Clinic; 🇺🇸 Houston, Texas, United States

Southwest Arthritis; 🇺🇸 Mesquite, Texas, United States

Sun Research Institute; 🇺🇸 San Antonio, Texas, United States

Clinica Adventista Belgrano; 🇦🇷 Belgrano, Argentina

Fundación Respirar Consultorio Médico Dr. Mariana Rivera; 🇦🇷 Buenos Aires, Argentina

Investigaciones Reumatológicas y Osteológicas; 🇦🇷 Caba, Argentina

Maffei Centro Medico; 🇦🇷 Ciudad Autónoma de Buenos Aires, Argentina

Fundación Respirar - Consultorios Médicos Dr. Doreski; 🇦🇷 Ciudad Autónoma de Buenos Aires, Argentina

Clínica Privada Vélez Sarsfield; 🇦🇷 Cordoba, Argentina

Hospital Italiano La Plata; 🇦🇷 La Plata, Argentina

Instituto de Reumatología; 🇦🇷 Mendoza, Argentina

Instituto de Investigaciones Clinicas Quilmes; 🇦🇷 Quilmes, Argentina

Centro Medico Privado de Reumatología; 🇦🇷 San Miguel de Tucumán, Argentina

Medical Center Artmed; 🇧🇬 Plovdiv, Bulgaria

Excelsior Medical Center; 🇧🇬 Sofia, Bulgaria

Diagnostic Consultative Center Aleksandrovska; 🇧🇬 Sofia, Bulgaria

Centro de Estudios Clínicos G y C; 🇨🇱 Providencia, Chile

Centros de Estudios Reumatológicos (CER); 🇨🇱 Providencia, Chile

Centro Internacional de Estudios Clínicos; 🇨🇱 Recoleta, Chile

Prosalud - Centro de Reumatología; 🇨🇱 Santiago, Chile

CeCim - Centro de Estudios Clínicos e Investigaciones Médicas; 🇨🇱 Santiago, Chile

Oncocentro APYS - Centro de Atención Médica Oncológica Integral; 🇨🇱 Viña del Mar, Chile

Hôpital Lapeyronie; 🇫🇷 Montpellier, France

Hôpital Emile Muller; 🇫🇷 Mulhouse, France

Hôpital Hautepierre; 🇫🇷 Strasbourg, France

New Plasma Clinic; 🇬🇪 Batumi, Georgia

Aversi Clinic - Central Branch; 🇬🇪 Tbilisi, Georgia

Jerarsi Clinic; 🇬🇪 Tbilisi, Georgia

Caucasus Medical Center; 🇬🇪 Tbilisi, Georgia

Clinic Innova LCC; 🇬🇪 Tbilisi, Georgia

Universitätsklinikum Düsseldorf; 🇩🇪 Düsseldorf, Germany

Universitätsmedizin der Johannes Gutenberg-Universität Mainz; 🇩🇪 Mainz, Germany

LMU Klinikum - Campus Innenstadt; 🇩🇪 München, Germany

Praxis Für Rheumatologie, Gastroenterologie Und Innere Medizin; 🇩🇪 München, Germany

Krankenhaus der Barmherzigen Brüder Trier; 🇩🇪 Trier, Germany

Qualiclinic Egeszsegugyi Szolgaltato es Kutatasszervezo; 🇭🇺 Budapest, Hungary

Békés Megyei Központi Kórház - Pándy Kálmán Tagkórház; 🇭🇺 Gyula, Hungary

Vital Medical Center - Reumatológia; 🇭🇺 Veszprém, Hungary

Clínica San Juan de Dios; 🇵🇪 Cayma, Peru

ACQ Medic S.A.C.; 🇵🇪 Jesús María, Peru

Hospital Militar Central Coronel Luis Arias Schreiber; 🇵🇪 Jesús María, Peru

Clínica Monterrico; 🇵🇪 Lima, Peru

Instituto Peruano Del Hueso Y La Articulacion; 🇵🇪 San Isidro, Peru

Clínica Anglo Americana - Sede San Isidro; 🇵🇪 San Isidro, Peru

Hospital Maria Auxiliadora; 🇵🇪 San Juan De Miraflores, Peru

Niepubliczny Zakład Opieki Zdrowotnej Bif-Med S.C.; 🇵🇱 Bytom, Poland

Centrum Medyczne Plejady; 🇵🇱 Kraków, Poland

Poradnie specjalistyczne REUMED Wallenroda; 🇵🇱 Lublin, Poland

AES - Synexus - Poznań; 🇵🇱 Poznań, Poland

Prywatna Praktyka Lekarska Prof. Dr Hab. Med. Paweł Hrycaj; 🇵🇱 Poznań, Poland

Trialmed CRS - Warszawa; 🇵🇱 Warszawa, Poland

Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. prof. dr hab. med. Eleonory Reicher; 🇵🇱 Warszawa, Poland

Klinika Reuma Park sp. z o.o. sp.k - Centrum Medyczne Reuma Park; 🇵🇱 Warszawa, Poland

AES - Synexus - Wrocław; 🇵🇱 Wrocław, Poland

FutureMeds - Wroclaw; 🇵🇱 Wrocław, Poland

Latin Clinical Trial Center; 🇵🇷 San Juan, Puerto Rico

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Hospital General Universitario Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Regional Universitario de Málaga - Hospital General; 🇪🇸 Málaga, Spain

Hospital de Mérida; 🇪🇸 Mérida, Spain

Hospital Universitario Virgen de Valme; 🇪🇸 Sevilla, Spain

Hospital Universitario Araba; 🇪🇸 Vitoria-Gasteiz, Spain