Clinical trial NCT05856448: A Study Evaluating the Effects of GLPG3667 Administered As Oral Treatment in Adult Participants with Active Systemic Lupus Erythematosus
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Orally Administered GLPG3667 in Adult Subjects with Active Systemic Lupus Erythematosus
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2023-05-12
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: Key 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.

Primary outcomes:
measure: Percentage of Participants who Achieved the SLE Responder Index (SRI)-4 Response at Week 32
timeFrame: Week 32
Secondary outcomes:
measure: Percentage of Participants who Achieved the SRI-4 Response at Week 48
timeFrame: Week 48
measure: Percentage of Participants who Achieved the British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response at Week 32 and Week 48
timeFrame: Week 32, Week 48
measure: 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
timeFrame: Week 32, Week 48
measure: Percentage of Participants who achieve Lupus Low Disease Activity State (LLDAS) at Week 32 and Week 48
timeFrame: Week 32, Week 48
measure: Change from Baseline in the 28-joint Count for Tender joints at Week 32 and Week 48
timeFrame: Baseline, Week 32 and Week 48
measure: Change from Baseline in the 28-joint Count for Swollen joints at Week 32 and Week 48
timeFrame: Baseline, Week 32 and Week 48
measure: Change from Baseline in the 28-joint Count for Tender + Swollen (active) joints at Week 32 and Week 48
timeFrame: Baseline, Week 32 and Week 48
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs leading to treatment discontinuation
timeFrame: From the start of first dose till 30 days after the last dose (up to 52 weeks)
measure: Pharmacokinetics (PK) of GLPG3667: Estimated Maximum Plasma Concentration (Cmax)
timeFrame: 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
measure: PK of GLPG3667: Estimated Area Under the Concentration Time Curve (AUC) at Steady State
timeFrame: 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
measure: PK of GLPG3667: Estimated Trough Concentration (Ctrough) at Steady State
timeFrame: 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
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona College of Medicine - Tucson
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Rancho Mirage
country: United States
facility: Desert Medical Advances
state: California
city: Simi Valley
country: United States
facility: Millennium Clinical Trials
state: California
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials
state: California
city: Upland
country: United States
facility: Upland Rheumatology Center
state: California
city: Aventura
country: United States
facility: Arthritis & Rheumatic Disease Specialties
state: Florida
city: DeBary
country: United States
facility: Omega Research DeBary
state: Florida
city: Kissimmee
country: United States
facility: Alloy Clinical Research, LLC
state: Florida
city: Miami
country: United States
facility: San Marcus Research Clinic
state: Florida
city: Miami
country: United States
facility: Advanced Pharma - Miami
state: Florida
city: Miami
country: United States
facility: Professional Research Center
state: Florida
city: Plantation
country: United States
facility: Integral Rheumatology & Immunology Specialists
state: Florida
city: Tampa
country: United States
facility: Alliance Clinical Research of Tampa
state: Florida
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials
state: New Mexico
city: Charlotte
country: United States
facility: DJL Clinical Research
state: North Carolina
city: Tulsa
country: United States
facility: Lynn Institute of Tulsa
state: Oklahoma
city: Knoxville
country: United States
facility: New Phase Research & Development
state: Tennessee
city: Memphis
country: United States
facility: Office of Ramesh C. Gupta MD / Shelby Research LLC - Tennessee
state: Tennessee
city: Houston
country: United States
facility: Care and Cure Clinic
state: Texas
city: Mesquite
country: United States
facility: Southwest Arthritis
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: Belgrano
country: Argentina
facility: Clinica Adventista Belgrano
city: Buenos Aires
country: Argentina
facility: Fundación Respirar Consultorio Médico Dr. Mariana Rivera
city: Caba
country: Argentina
facility: Investigaciones Reumatológicas y Osteológicas
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Maffei Centro Medico
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: Fundación Respirar - Consultorios Médicos Dr. Doreski
city: Cordoba
country: Argentina
facility: Clínica Privada Vélez Sarsfield
city: La Plata
country: Argentina
facility: Hospital Italiano La Plata
city: Mendoza
country: Argentina
facility: Instituto de Reumatología
city: Quilmes
country: Argentina
facility: Instituto de Investigaciones Clinicas Quilmes
city: San Miguel de Tucumán
country: Argentina
facility: Centro Medico Privado de Reumatología
city: Plovdiv
country: Bulgaria
facility: Medical Center Artmed
city: Sofia
country: Bulgaria
facility: Excelsior Medical Center
city: Sofia
country: Bulgaria
facility: Diagnostic Consultative Center Aleksandrovska
city: Providencia
country: Chile
facility: Centro de Estudios Clínicos G y C
city: Providencia
country: Chile
facility: Centros de Estudios Reumatológicos (CER)
city: Recoleta
country: Chile
facility: Centro Internacional de Estudios Clínicos
city: Santiago
country: Chile
facility: Prosalud - Centro de Reumatología
city: Santiago
country: Chile
facility: CeCim - Centro de Estudios Clínicos e Investigaciones Médicas
city: Viña del Mar
country: Chile
facility: Oncocentro APYS - Centro de Atención Médica Oncológica Integral
city: Montpellier
country: France
facility: Hôpital Lapeyronie
city: Mulhouse
country: France
facility: Hôpital Emile Muller
city: Strasbourg
country: France
facility: Hôpital Hautepierre
city: Batumi
country: Georgia
facility: New Plasma Clinic
city: Tbilisi
country: Georgia
facility: Aversi Clinic - Central Branch
city: Tbilisi
country: Georgia
facility: Jerarsi Clinic
city: Tbilisi
country: Georgia
facility: Caucasus Medical Center
city: Tbilisi
country: Georgia
facility: Clinic Innova LCC
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: München
country: Germany
facility: LMU Klinikum - Campus Innenstadt
city: München
country: Germany
facility: Praxis Für Rheumatologie, Gastroenterologie Und Innere Medizin
city: Trier
country: Germany
facility: Krankenhaus der Barmherzigen Brüder Trier
city: Budapest
country: Hungary
facility: Qualiclinic Egeszsegugyi Szolgaltato es Kutatasszervezo
city: Gyula
country: Hungary
facility: Békés Megyei Központi Kórház - Pándy Kálmán Tagkórház
city: Veszprém
country: Hungary
facility: Vital Medical Center - Reumatológia
city: Cayma
country: Peru
facility: Clínica San Juan de Dios
city: Jesús María
country: Peru
facility: ACQ Medic S.A.C.
city: Jesús María
country: Peru
facility: Hospital Militar Central Coronel Luis Arias Schreiber
city: Lima
country: Peru
facility: Clínica Monterrico
city: San Isidro
country: Peru
facility: Instituto Peruano Del Hueso Y La Articulacion
city: San Isidro
country: Peru
facility: Clínica Anglo Americana - Sede San Isidro
city: San Juan De Miraflores
country: Peru
facility: Hospital Maria Auxiliadora
city: Bytom
country: Poland
facility: Niepubliczny Zakład Opieki Zdrowotnej Bif-Med S.C.
city: Kraków
country: Poland
facility: Centrum Medyczne Plejady
city: Lublin
country: Poland
facility: Poradnie specjalistyczne REUMED Wallenroda
city: Poznań
country: Poland
facility: AES - Synexus - Poznań
city: Poznań
country: Poland
facility: Prywatna Praktyka Lekarska Prof. Dr Hab. Med. Paweł Hrycaj
city: Warszawa
country: Poland
facility: Trialmed CRS - Warszawa
city: Warszawa
country: Poland
facility: Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. prof. dr hab. med. Eleonory Reicher
city: Warszawa
country: Poland
facility: Klinika Reuma Park sp. z o.o. sp.k - Centrum Medyczne Reuma Park
city: Wrocław
country: Poland
facility: AES - Synexus - Wrocław
city: Wrocław
country: Poland
facility: FutureMeds - Wroclaw
city: San Juan
country: Puerto Rico
facility: Latin Clinical Trial Center
city: San Juan
country: Puerto Rico
facility: GCM Medical Group
city: Badajoz
country: Spain
facility: Hospital Universitario de Badajoz
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga - Hospital General
city: Mérida
country: Spain
facility: Hospital de Mérida
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de Valme
city: Vitoria-Gasteiz
country: Spain
facility: Hospital Universitario Araba
Study officials:
affiliation: Galapagos NV
name: Galapagos Study Director
role: STUDY_DIRECTOR
References: