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

• ClinicalTrials.gov Identifier: NCT05856448
• Recruitment Status: Recruiting
• First Posted: May 12, 2023
• Last Update Posted: May 14, 2024
• Sponsor: Galapagos NV
• Information provided by (Responsible Party): Galapagos NV

Tracking Information

• First Submitted Date: May 3, 2023
• First Posted Date: May 12, 2023
• Last Update Posted Date: May 14, 2024
• Actual Study Start Date: June 28, 2023
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 4, 2023): Percentage of Participants who Achieved the SLE Responder Index (SRI)-4 Response at Week 32 [ Time Frame: Week 32 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 18, 2023)

• Percentage of Participants who Achieved the SRI-4 Response at Week 48 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Week 32, Week 48 ]
• Percentage of Participants who achieve Lupus Low Disease Activity State (LLDAS) at Week 32 and Week 48 [ Time Frame: Week 32, Week 48 ]
• Change from Baseline in the 28-joint Count for Tender joints at Week 32 and Week 48 [ Time Frame: Baseline, Week 32 and Week 48 ]
• Change from Baseline in the 28-joint Count for Swollen joints at Week 32 and Week 48 [ Time Frame: 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 [ Time Frame: Baseline, Week 32 and Week 48 ]
• Number of Participants with Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs leading to treatment discontinuation [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 ]

Original Secondary Outcome Measures (submitted: May 4, 2023)

• Percentage of Participants who Achieved the British Isles Lupus Assessment Group (BILAG) -Based Composite Lupus Assessment (BICLA) Response at Week 32 [ Time Frame: Week 32 ]
• Percentage of Participants with >=50% Reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score at Week 16 [ Time Frame: Week 16 ]
• Percentage of Participants who achieve Lupus Low Disease Activity State (LLDAS) at Week 32 [ Time Frame: Week 32 ]
• Change from Baseline in the 28-joint Count for Tender joints at Week 32 [ Time Frame: Baseline, Week 32 ]
• Change from Baseline in the 28-joint Count for Swollen joints at Week 32 [ Time Frame: Baseline, Week 32 ]
• Change from Baseline in the 28-joint Count for Tender + Swollen (active) joints at Week 32 [ Time Frame: Baseline, Week 32 ]
• Number of Participants with Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs leading to treatment discontinuation [ Time Frame: From the start of first dose till 30 days after the last dose (up to 36 weeks) ]
• Pharmacokinetics (PK) of GLPG3667: Estimated Maximum Plasma Concentration (Cmax) [ Time Frame: Predose every 4 weeks from Week 2 to Week 32 and 0.5hours (h)-2h , 2h-4h , 4h-6h postdose at Week 4 ]
• PK of GLPG3667: Estimated Area Under the Concentration Time Curve (AUC) at Steady State [ Time Frame: Predose every 4 weeks from Week 2 to Week 32 and 0.5hours (h)-2h , 2h-4h , 4h-6h postdose at Week 4 ]
• PK of GLPG3667: Estimated Trough Concentration (Ctrough) at Steady State [ Time Frame: Predose every 4 weeks from Week 2 to Week 32 and 0.5hours (h)-2h , 2h-4h , 4h-6h postdose at Week 4 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Systemic Lupus Erythematosus

Intervention

• Drug: GLPG3667
  Capsule
• Drug: Placebo
  Capsule

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 18, 2023): 180
• Original Estimated Enrollment (submitted: May 4, 2023): 140
• Estimated Study Completion Date: April 2026
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Galapagos Medical Information; +3215342900; medicalinfo@glpg.com

• Listed Location Countries: Argentina, Bulgaria, Chile, France, Georgia, Germany, Hungary, Peru, Poland, Puerto Rico, Spain, United States

Administrative Information

• NCT Number: NCT05856448
• Other Study ID Numbers: GLPG3667-CL-215; 2023-503183-16-00 ( EU Trial (CTIS) Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Galapagos NV
• Original Responsible Party: Same as current
• Current Study Sponsor: Galapagos NV
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Galapagos Study Director; Galapagos NV

• PRS Account: Galapagos NV
• Verification Date: May 2024