A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety and Efficacy of Filgotinib and GS-9876 in Female Subjects with Moderately-to-Severely Active Cutaneous Lupus Erythematosus (CLE)

What we are studying

Filgotinib is an orally administered, small molecule inhibitor of JAK1, an intracellular TYK dysregulated in subjects with inflammatory disorders. Filgotinib has demonstrated clinical activity and a favorable safety and tolerability profile in Phase 2 studies in subjects with moderately to severely active RA. Janus kinase 1 activation is required for type I interferon (IFN) signaling, which is thought to be central to both systemic and cutaneous lupus. Further, in vivo studies using a JAK1/JAK2 inhibitor (ruxolitinib) attenuated the development of skin lesions in the MRL/lpr mouse model of lupus. Given its central role in immune cell signaling, inhibition of SYK is expected to have pleiotropic anti-inflammatory effects and affect multiple steps in CLE pathogenesis. B cells have been implicated in the pathogenesis of CLE as demonstrated by an increased number of B cells in the peripheral blood and lesions of individuals with DLE. B cell depletion demonstrates an effect in individuals with certain types of CLE. As a critical mediator of BCR signaling, SYK inhibition suppresses BCR-stimulated proliferation, co-stimulatory molecule expression, and autoantibody production. Phosphorylated SYK and SYK-associated genes are highly expressed in several cell types in CLE skin including keratinocytes and infiltrating immune cells. Further, inhibiting SYK in vitro decreases keratinocyte expression of pro-inflammatory cytokines. Spleen tyrosine kinase inhibition in two lupus-prone mouse models (MRL/lpr and BAK/BAX) suppresses skin disease. The primary objective of this study is as follows: To evaluate the efficacy of filgotinib and GS-9876 in female subjects with moderately-to-severely active cutaneous lupus erythematosus (CLE). The secondary objective of this study is as follows: To evaluate the safety and tolerability of filgotinib and GS-9876 in moderately-to-severely active CLE. The exploratory objectives of this study are as follows: To characterize the pharmacokinetics (PK) of filgotinib and GS-9876 in moderately-to-severely active CLE, To evaluate the effect of filgotinib and GS-9876 on patient-reported outcomes in CLE, including disability and quality of life, To evaluate the effect of filgotinib and GS-9876 on peripheral blood and histologic markers of inflammation, To evaluate the association of inflammatory biomarkers with clinical outcomes, To characterize the association of host genetics and other markers with disease severity, disease progression, and treatment response to filgotinib and GS-9876 in CLE.

Who is Eligible

  • Genders:
    • Women
  • Races:
    • White
    • African American
    • American Indian or Alaska Native
    • Native Hawaiian or Pacific Islander
  • All Ethnicities
  • Ages 18 - 75

Eligibility Criteria

  • If of childbearing potential have negative pregnancy and agree to use specified method(s) of contraception
  • Diagnosis of Moderately-to-severely activeCLE (CCLE (eg
  • DLE) or SCLE)
  • Per investigator evaluation
  • Prior intolerance or inadequate response to at least one of the following medications for the treatment of CLE | Topical corticosteroids or topical tacromilus
  • Administered for ? 3 months; Oral corticosteroids ? 10 mg/day taken for ? 3 months; Antirheumatic drug (csDMARD) (including
  • But not limited to chloroquine; quinicrine; hyoxychloroquine; zathioprine; mycophenolate; leflunomide; dapsone; or MTX)administered for ? 3 months
  • Bdmard (such as belimumab or abatacept) administered for ? 3 months or ? 1 dose of rituximab
  • No Major surgery within past 30 days
  • No History of malignancy within the last 5 yrs prior to screening (except for successfully treated basal cell or non-metastatic squamous cell skin cancer
  • HIV
  • HCV
  • Hepatitis B negative

What is involved

  • Study will last 52 weeks (1 year) not including Screening Visit
  • Required to visit the clinic at least 14 times
  • Visits include: blood work; chest x-ray; ECG; physical exam; and lupus evaluation

Compensation

You will be paid $2250.00 if you complete all visits. If you withdraw before completion of the study you will be paid as follows for each complete study visit. Travel: $50.00 per visit; Study Visit Participation: $100.00 per visit; Meals: $30.00 per visi

Contact Information

Study Coordinator
Pat Wagoner
Email
pwagoner@wakehealth.edu
Phone
336-716-3775
Principal Investigator
William Huang

Disclaimer: The information on this website is for general informational purposes only and SHOULD NOT be relied upon as a substitute for sound professional medical advice, evaluation or care from your physician or other qualified health care provider.