A study evaluating the effects of GLPG3667 given as oral treatment in adults with active systemic lupus erythematosus.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Galapagos

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12]

Trial duration

16 Jan 2024 → 27 Feb 2026

Decision date (initial)

2023-12-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Galapagos NV

External identifiers

EU CT number

2023-503183-16-00

ClinicalTrials.gov

NCT05856448

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Pharmacokinetic, Safety, Pharmacodynamic

- To evaluate the efficacy of GLPG3667 compared to placebo on disease activity in subjects with active systemic lupus erythematosus (SLE).

Secondary objectives 3

1. - To further characterize the efficacy of GLPG3667 compared to placebo in subjects with active SLE.
2. - To evaluate the safety and tolerability of GLPG3667 in subjects with active SLE.
3. - To characterize the pharmacokinetics of GLPG3667 in subjects with active SLE.

Conditions and MedDRA coding

Systemic Lupus Erythematosus

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. - Female or male subjects from 18 to 75 years of age inclusive, on the date of signing the informed consent form (ICF).
2. - 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.
3. - 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.
4. - 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.
5. - 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.
6. - 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 14

1. - 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.
2. - 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.
3. - 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.
4. - Drug-induced systemic lupus erythematosus.
5. - 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).
6. - 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.
7. - 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).
8. - 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.
9. - 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.
10. - Subject with poorly controlled chronic cardiac, pulmonary, or renal disease.
11. - 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).
12. - Prior exposure to tyrosine kinase 2 (TYK2) inhibitors.
13. - Female subject is pregnant or breast feeding or intending to become pregnant or breastfeed during the study.
14. - Subject has taken any prohibited therapies within the defined washout periods before screening, and during screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. - Proportion of subjects who achieved the SLE responder index (SRI)-4 response at Week 32.

Secondary endpoints 7

1. - Proportion of subjects who achieved the SRI-4 response at Week 48.
2. - Proportion of subjects who achieved the British Isles Lupus Assessment Group (BILAG)-based Composite Lupus Assessment (BICLA) response at Week 32 and Week 48
3. - Proportion of subjects with >=50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-A score at Week 32 and Week 48 .
4. - Proportion of subjects who achieve Lupus Low Disease Activity State (LLDAS) at Week 32 and Week 48.
5. - Change from baseline in the 28-joint count for tender, swollen, and tender + swollen (active) joints at Week 32 and Week 48.
6. - Treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events, and TEAEs leading to treatment discontinuation.
7. - Estimated GLPG3667 maximum plasma concentration, area under the plasma concentration-time curve, and trough plasma concentration at steady-state.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Galapagos

Sponsor organisation

Galapagos

Address

Generaal De Wittelaan L11 A3

City

Mechelen

Postcode

2800

Country

Belgium

Scientific contact point

Organisation

Galapagos

Contact name

Galapagos Medical Information

Public contact point

Organisation

Galapagos

Contact name

Galapagos Medical Information

Third parties 3

Locations

6 EU/EEA countries · 32 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 43 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications