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

Systemic Lupus Erythematosus Clinical Trial

— GALACELA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05856448
• Other study ID #: GLPG3667-CL-215
• Secondary ID: 2023-503183-16-0
• Status: Recruiting
• Phase: Phase 2
• Start date: June 28, 2023
• Est. completion date: April 2026

Study information

• Verified date: June 2024
• Source: Galapagos NV
• Contact: Galapagos Medical Information
• Phone: +3215342900
• Email: medicalinfo[@]glpg.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: April 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Drug:
• GLPG3667
Capsule
• Placebo
Capsule

Locations

Country	Name	City	State
Argentina	Clinica Adventista Belgrano	Belgrano
Argentina	Fundación Respirar Consultorio Médico Dr. Mariana Rivera	Buenos Aires
Argentina	Investigaciones Reumatológicas y Osteológicas	Caba
Argentina	Fundación Respirar - Consultorios Médicos Dr. Doreski	Ciudad Autónoma de Buenos Aires
Argentina	Maffei Centro Medico	Ciudad Autónoma de Buenos Aires
Argentina	Instituto de Reumatología	Mendoza
Argentina	Instituto de Investigaciones Clinicas Quilmes	Quilmes
Argentina	Centro Medico Privado de Reumatología	San Miguel de Tucumán
Bulgaria	Medical Center Artmed	Plovdiv
Bulgaria	Diagnostic Consultative Center Aleksandrovska	Sofia
Bulgaria	Excelsior Medical Center	Sofia
Chile	Centros de Estudios Reumatológicos (CER)	Providencia
Chile	Centro Internacional de Estudios Clínicos	Recoleta
Chile	Prosalud - Centro de Reumatología	Santiago
Chile	Oncocentro APYS - Centro de Atención Médica Oncológica Integral	Viña del Mar
France	Hôpital Lapeyronie	Montpellier
France	Hôpital Emile Muller	Mulhouse
France	Hôpital Hautepierre	Strasbourg
Georgia	New Plasma Clinic	Batumi
Georgia	Aversi Clinic - Central Branch	Tbilisi
Georgia	Caucasus Medical Center	Tbilisi
Georgia	Clinic Innova LCC	Tbilisi
Georgia	Jerarsi Clinic	Tbilisi
Germany	LMU Klinikum - Campus Innenstadt	München
Germany	Praxis Für Rheumatologie, Gastroenterologie Und Innere Medizin	München
Germany	Krankenhaus der Barmherzigen Brüder Trier	Trier
Hungary	Qualiclinic Egeszsegugyi Szolgaltato es Kutatasszervezo	Budapest
Hungary	Vital Medical Center - Reumatológia	Veszprém
Peru	Clínica Monterrico	Lima
Poland	Niepubliczny Zaklad Opieki Zdrowotnej Bif-Med S.C.	Bytom
Poland	Centrum Medyczne Plejady	Kraków
Poland	Poradnie specjalistyczne REUMED Wallenroda	Lublin
Poland	Prywatna Praktyka Lekarska Prof. Dr Hab. Med. Pawel Hrycaj	Poznan
Poland	Klinika Reuma Park sp. z o.o. sp.k - Centrum Medyczne Reuma Park	Warszawa
Poland	Narodowy Instytut Geriatrii, Reumatologii i Rehabilitacji im. prof. dr hab. med. Eleonory Reicher	Warszawa
Poland	Trialmed CRS - Warszawa	Warszawa
Poland	AES - Synexus - Wroclaw	Wroclaw
Poland	FutureMeds - Wroclaw	Wroclaw
Puerto Rico	Latin Clinical Trial Center	San Juan
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
United States	Albuquerque Clinical Trials	Albuquerque	New Mexico
United States	Arthritis & Rheumatic Disease Specialties	Aventura	Florida
United States	DJL Clinical Research	Charlotte	North Carolina
United States	Omega Research DeBary	DeBary	Florida
United States	Care and Cure Clinic	Houston	Texas
United States	Alloy Clinical Research, LLC	Kissimmee	Florida
United States	New Phase Research & Development	Knoxville	Tennessee
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	Southwest Arthritis	Mesquite	Texas
United States	Advanced Pharma - Miami	Miami	Florida
United States	Professional Research Center	Miami	Florida
United States	San Marcus Research Clinic	Miami	Florida
United States	Integral Rheumatology & Immunology Specialists	Plantation	Florida
United States	Desert Medical Advances	Rancho Mirage	California
United States	Sun Research Institute	San Antonio	Texas
United States	Millennium Clinical Trials	Simi Valley	California
United States	Alliance Clinical Research of Tampa	Tampa	Florida
United States	University of Arizona College of Medicine - Tucson	Tucson	Arizona
United States	Lynn Institute of Tulsa	Tulsa	Oklahoma
United States	Inland Rheumatology Clinical Trials	Upland	California
United States	Upland Rheumatology Center	Upland	California

Sponsors (1)

Lead Sponsor	Collaborator
Galapagos NV

Countries where clinical trial is conducted

United States,  Argentina,  Bulgaria,  Chile,  France,  Georgia,  Germany,  Hungary,  Peru,  Poland,  Puerto Rico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants who Achieved the SLE Responder Index (SRI)-4 Response at Week 32		Week 32
Secondary	Percentage of Participants who Achieved the SRI-4 Response at Week 48		Week 48
Secondary	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
Secondary	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
Secondary	Percentage of Participants who achieve Lupus Low Disease Activity State (LLDAS) at Week 32 and Week 48		Week 32, Week 48
Secondary	Change from Baseline in the 28-joint Count for Tender joints at Week 32 and Week 48		Baseline, Week 32 and Week 48
Secondary	Change from Baseline in the 28-joint Count for Swollen joints at Week 32 and Week 48		Baseline, Week 32 and Week 48
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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