Efficacy and Safety of Filgotinib in Adults With Active Noninfectious Uveitis (Humboldt)

• ClinicalTrials.gov Identifier: NCT03207815
• Recruitment Status: Recruiting
• First Posted: July 5, 2017
• Last Update Posted: October 11, 2019
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: June 30, 2017
• First Posted Date: July 5, 2017
• Last Update Posted Date: October 11, 2019
• Actual Study Start Date: July 26, 2017
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 13, 2017)

Proportion of Participants Failing Treatment for Active NonInfectious Uveitis by Week 24 [ Time Frame: Baseline to Week 24 ]

Treatment failure will be defined as a participant meeting at least one of the following criteria in at least one eye:

• New active, inflammatory lesions relative to Day 1/Baseline (during all visits beginning Week 6 visit)
• Inability to achieve ≤ grade 0.5+ (at Week 6); or 2-step increase (all visits after Week 6) relative to best state achieved in Anterior Chamber Cell grade (SUN Criteria)
• Inability to achieve ≤ grade 0.5+ (at Week 6); or 2-step increase (all visits after Week 6) relative to best state achieved in Vitreous Haze (VH) grade (NEI/SUN Criteria)
• Worsening of best corrected visual acuity (BCVA) by ≥ 15 letters relative to best state achieved (during all visits beginning at Week 6 visit)

Original Primary Outcome Measures (submitted: June 30, 2017)

Proportion of Participants Failing Treatment for Active Non-Infectious Uveitis by Week 24 [ Time Frame: Baseline to Week 24 ]

Treatment failure will be defined as a participant meeting at least one of the following criteria in at least one eye:

• New active, inflammatory lesions relative to Day 1/Baseline (during all visits beginning Week 6 visit)
• Inability to achieve ≤ grade 0.5 (at Week 6); or 2-step increase (all visits after Week 6) relative to best state achieved in Anterior Chamber Cell grade (SUN Criteria)
• Inability to achieve ≤ grade 0.5 (at Week 6); or 2-step increase (all visits after Week 6) relative to best state achieved in Vitreous Haze (VH) grade (NEI/SUN Criteria)
• Worsening of best corrected visual acuity (BCVA) by ≥ 15 letters relative to best state achieved (during all visits beginning at Week 6 visit)

• Change History: Complete list of historical versions of study NCT03207815 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: December 13, 2017)

• Time to Treatment Failure on or After Week 6 [ Time Frame: Baseline to Week 52 ]
  Treatment failure will be defined as a participant meeting at least one of the following criteria in at least one eye:

  • New active, inflammatory lesions relative to Day 1/Baseline (during all visits beginning Week 6 visit)
  • Inability to achieve ≤ grade 0.5+ (at Week 6); or 2-step increase (all visits after Week 6) relative to best state achieved in Anterior Chamber Cell grade (SUN Criteria)
  • Inability to achieve ≤ grade 0.5+ (at Week 6); or 2-step increase (all visits after Week 6) relative to best state achieved in VH grade (NEI/SUN Criteria)
  • Worsening of best corrected visual acuity (BCVA) by ≥ 15 letters relative to best state achieved (during all visits beginning at Week 6 visit)
• Change in VH Grade in Each Eye (NEI/SUN criteria), from Best State Achieved Prior to Week 6 to Week 52 or End of Treatment (EOT) visit [ Time Frame: Baseline to Week 52 ]
• Change in Anterior Chamber (AC) Cell Grade in Each Eye, from Best State Achieved Prior to Week 6 to Week 52 or EOT Visit [ Time Frame: Baseline to Week 52 ]
• Change in Logarithm of the Minimal Angle of Resolution (logMAR) BCVA in Each Eye, from Best State Achieved Prior to Week 6 to Week 52 or EOT Visit [ Time Frame: Baseline to Week 52 ]
• Log Change in Central Retinal Thickness in Each Eye, from Best State Achieved Prior to Week 6 to Week 52 or EOT Visit [ Time Frame: Baseline to Week 52 ]
• Time to Development of Macular Edema in At Least One Eye on or After Week 6 [ Time Frame: Baseline to Week 52 ]
  Macular edema is determined by optical coherence tomography (OCT)
• Pharmacokinetic Plasma Concentrations of Filgotinib and its Metabolite GS-829845 [ Time Frame: Baseline to Week 52 ]

Original Secondary Outcome Measures (submitted: June 30, 2017)

• Time to Treatment Failure on or After Week 6 [ Time Frame: Baseline to Week 52 ]
  Treatment failure will be defined as a participant meeting at least one of the following criteria in at least one eye:

  • New active, inflammatory lesions relative to Day 1/Baseline (during all visits beginning Week 6 visit)
  • Inability to achieve ≤ grade 0.5 (at Week 6); or 2-step increase (all visits after Week 6) relative to best state achieved in Anterior Chamber Cell grade (SUN Criteria)
  • Inability to achieve ≤ grade 0.5 (at Week 6); or 2-step increase (all visits after Week 6) relative to best state achieved in VH grade (NEI/SUN Criteria)
  • Worsening of best corrected visual acuity (BCVA) by ≥ 15 letters relative to best state achieved (during all visits beginning at Week 6 visit)
• Change in VH Grade in Each Eye (NEI/SUN criteria), from Best State Achieved Prior to Week 6 to Week 52 or End of Treatment (EOT) visit [ Time Frame: Baseline to Week 52 ]
• Change in Anterior Chamber (AC) Cell Grade in Each Eye, from Best State Achieved Prior to Week 6 to Week 52 or EOT Visit [ Time Frame: Baseline to Week 52 ]
• Change in Logarithm of the Minimal Angle of Resolution (logMAR) BCVA in Each Eye, from Best State Achieved Prior to Week 6 to Week 52 or EOT Visit [ Time Frame: Baseline to Week 52 ]
• Log Change in Central Retinal Thickness in Each Eye, from Best State Achieved Prior to Week 6 to Week 52 or EOT Visit [ Time Frame: Baseline to Week 52 ]
• Time to Development of Macular Edema in At Least One Eye on or After Week 6 [ Time Frame: Baseline to Week 52 ]
  Macular edema is determined by optical coherence tomography (OCT)
• Pharmacokinetic Plasma Concentrations of Filgotinib and its Metabolite GS-829845 [ Time Frame: Baseline to Week 52 ]

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

Descriptive Information

• Brief Title: Efficacy and Safety of Filgotinib in Adults With Active Noninfectious Uveitis
• Official Title: A Phase 2, Randomized, Placebo-Controlled Trial Evaluating the Efficacy and Safety of Filgotinib in Subjects With Active Noninfectious Uveitis
• Brief Summary: The primary objective of this study is to evaluate the efficacy of filgotinib versus placebo for the treatment of the signs and symptoms of noninfectious uveitis in participants failing treatment for active noninfectious uveitis.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Noninfectious Uveitis

Intervention

• Drug: Filgotinib
  200 mg tablet(s) administered orally once daily
  Other Names:

  • GS-6034
  • GLPG0634
• Drug: Placebo to match filgotinib
  Tablet(s) administered orally once daily
• Drug: Prednisone
  Tablet(s) administered orally once daily

Study Arms

• Experimental: Filgotinib

  All participants will receive a standardized prednisone burst of 60 mg/day at Day 1/Baseline followed by a protocol-defined mandatory taper schedule, to Week 15.

  All participants will receive filgotinib for up to 52 weeks.

  Interventions:

  • Drug: Filgotinib
  • Drug: Prednisone
• Placebo Comparator: Placebo

  All participants will receive a standardized prednisone burst of 60 mg/day at Day 1/Baseline followed by a protocol-defined mandatory taper schedule, to Week 15.

  All participants will receive placebo to match filgotinib for up to 52 weeks.

  Interventions:

  • Drug: Placebo to match filgotinib
  • Drug: Prednisone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 30, 2017): 110
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2022
• Estimated Primary Completion Date: December 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Is diagnosed with active noninfectious intermediate-, posterior-, or pan-uveitis

• Must have active uveitic disease at the Day 1/Baseline visit as defined by the presence of at least 1 of the following parameters in at least one eye despite 2 weeks of maintenance therapy with oral prednisone (≥ 10 mg/day to ≤ 60 mg/day) or an oral corticosteroid equivalent:

  • Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion
  • ≥ 2+ anterior chamber cells per the Standardization of Uveitis Nomenclature (SUN) criteria
  • ≥ 2+ vitreous haze per the National Eye Institute/Standardization of Uveitis Nomenclature (NEI/SUN) criteria
• No evidence of active tuberculosis (TB), history of prior TB or latent TB meeting the screening criteria

Key Exclusion Criteria:

• Elevated intraocular pressures and/or severe glaucoma at screening
• Confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to TB, cytomegalovirus (CMV), Human T-Lymphotropic Virus Type 1 (HTLV-1), Whipple's disease, Herpes Zoster virus (HZV), Lyme disease, toxoplasmosis and herpes simplex virus (HSV)
• Adults in whom anti-tumor necrosis factor (TNF) therapy has failed in controlling uveitis (as determined by the investigator) or previous exposure to any biologic therapy (except intravitreal anti-vascular endothelial growth factor (VEGF) therapy) with a potential therapeutic impact on noninfectious uveitis within 90 days of Day 1/ Baseline are not eligible to participate

Note: Other protocol defined Inclusion/ Exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Gilead Clinical Study Information Center; 1-833-445-3230 (GILEAD-0); GileadClinicalTrials@gilead.com

• Listed Location Countries: Australia, Canada, Germany, Israel, New Zealand, United Kingdom, United States

Administrative Information

• NCT Number: NCT03207815
• Other Study ID Numbers: GS-US-432-4097; 2017-001485-17 ( EudraCT 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: Not Provided
• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: October 2019