Study to Evaluate the Efficacy and Safety of Filgotinib in Adults With Active Noninfectious Uveitis (HUMBOLDT)

A Phase 2, Randomized, Placebo-Controlled Trial Evaluating the Efficacy and Safety of Filgotinib in Subjects With Active Noninfectious Uveitis

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 as measured by the percentage of participants failing treatment for active noninfectious uveitis by Week 24.

Study Overview

• Status: Terminated
• Conditions: Noninfectious Uveitis
• Intervention / Treatment: Drug: Filgotinib; Drug: Prednisone; Drug: Placebo to match filgotinib

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Lions Eye Institute
• Canada
  • Vancouver, Canada, V5Z 0E9
    • Retina Consultants
• Germany
  • Münster, Germany
    • St. Franziskus Hospital
• Israel
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center
• New Zealand
  • Remuera, New Zealand, 1050
    • Auckland Eye
• United Kingdom
  • Liverpool, United Kingdom, L7 8XP
    • Royal Liverpool University Hospital
  • London, United Kingdom
    • Moorfields Eye Hospital NHS Foundation Trust
  • Manchester, United Kingdom, M13 9WL
    • Central Mancester Hospitals NHS Foundation Trust, Manchester Royal Eye Hospital
  • Oxford, United Kingdom, OX3 9DU
    • Eye Research Group Oxford, Oxford Eye Hospital
• United States
  • California
    • Palo Alto, California, United States, 94303
      • Stanford Byers Eye Institute
  • Colorado
    • Golden, Colorado, United States, 80401
      • Colorado Retina Associates PC
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Medical Group
    • Oak Park, Illinois, United States, 60304
      • Illinois Retina Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Ophthalmic Consultants of Boston
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Associated Retinal Consultants PC
  • New Jersey
    • Palisades Park, New Jersey, United States, 07650
      • Metropolitan Eye Research and Surgery Institute
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Eye Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44191
      • Cleveland Clinic Foundation-Cole Eye Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Science University-Casey Eye Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Mid Atlantic Retina
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Texas Retina Associates - Fort Worth
    • San Antonio, Texas, United States, 78240
      • Foresight Studies, LLC
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin-Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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) or untreated latent TB

Key Exclusion Criteria:

• Participants with elevated intraocular pressures and/or severe glaucoma
• 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)

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Filgotinib; Participants will receive filgotinib 200 milligrams (mg) once daily for up to 52 weeks along with a standardized prednisone burst of 60 milligrams per day (mg/day) at Day 1/Baseline followed by a protocol-defined mandatory taper schedule up to Week 15.	Drug: Filgotinib; Tablet(s) administered orally; Other Names: GS-6034; GLPG0634; Drug: Prednisone; Tablet(s) administered orally
Placebo Comparator: Placebo; Participants will receive placebo to match filgotinib once daily for up to 52 weeks along with a standardized prednisone burst of 60 mg/day at Day 1/Baseline followed by a protocol-defined mandatory taper schedule up to Week 15.	Drug: Prednisone; Tablet(s) administered orally; Drug: Placebo to match filgotinib; Tablet(s) administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Failing Treatment for Active NonInfectious Uveitis by Week 24	Treatment failure was a participant meeting at least 1 of these criteria in at least 1 eye: New active, inflammatory lesions relative to Day 1/Baseline (all visits starting Week (Wk) 6); Inability to achieve ≤Grade 0.5+ (at Wk 6) or 2-step increase (change of Grade 0 to Grade 2+/Grade 0.5+ to Grade 3+) (all visits after Wk 6) relative to best state (RBS) achieved in Anterior Chamber (AC) cell grade (Standardization of Uveitis Nomenclature [SUN] criteria)[AC cell grades range from 0 (0 cells) to 4+ (>50 cells), higher scores=severe uveitis]; Inability to achieve ≤Grade 0.5+ (at Wk 6) or 2-step increase (all visits after Wk 6) RBS achieved in Vitreous Haze (VH) grade (National Eye Institute [NEI]/SUN criteria)[VH grades range from 0 (no evident VH) to 4+ (optic nerve head is obscured), higher scores=severe uveitis]; Worsening of best corrected visual acuity (BCVA) by ≥15 letters RBS achieved (all visits starting Wk 6), measured by an eye chart, fewer correct letters=severe uveitis.	Week 6 through Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Treatment Failure on or After Week 6	Treatment failure was a participant meeting at least 1 of these criteria in at least 1 eye: New active, inflammatory lesions relative to Day 1/Baseline (all visits starting Wk 6); Inability to achieve ≤Grade 0.5+ (at Wk 6) or 2-step increase (change of Grade 0 to Grade 2+/Grade 0.5+ to Grade 3+) (all visits after Wk 6) relative to best state (RBS) achieved in AC cell grade (SUN criteria) [AC cell grades range from 0 (0 cells) to 4+ (>50 cells), higher scores=severe uveitis]; Inability to achieve ≤Grade 0.5+ (at Wk 6) or 2-step increase (all visits after Wk 6) RBS achieved in VH grade (NEI/SUN criteria) [VH grades range from 0 (no evident VH) to 4+ (optic nerve head is obscured), higher scores=severe uveitis]; Worsening of BCVA by ≥15 letters RBS achieved (all visits starting Wk 6), measured by an eye chart, fewer correct letters=severe uveitis.	Week 6 through Week 52
Change in Vitreous Haze (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 or Early Termination (ET)	Grading of VH was based on the publication from the NEI which has also been adapted by the SUN working group. VH grades range from 0 (no evident VH) to 4+ (optic nerve head is obscured), with higher scores indicating greater severity of uveitis. A negative change from best state value obtained prior to Week 6 indicates improvement.	Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks)
Change in Anterior Chamber (AC) Cell Grade in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET	The number of AC cells observed within a 1 mm × 1 mm slit beam were recorded for each eye. The reported number was used to determine the grade according to the SUN criteria. AC cell grades range from 0 (0 cells in field) to 4+ (>50 cells in field), with higher scores indicating more cells visible in the AC and greater severity of uveitis. A negative change from best state value obtained prior to Week 6 indicates improvement.	Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks)
Change in Logarithm of the Minimal Angle of Resolution (logMAR) Best Corrected Visual Acuity (BCVA) in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET	BCVA is the best possible vision that an eye can achieve with the set of glasses or contact lenses. A refraction test was performed to measure the appropriate lens strength to focus light on the retina. Using the appropriate corrective lenses based on that visit's refraction, participant's BCVA was measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. In the ETDRS system, 15 letters is equal to a change in 3 lines of visual acuity. If the participant is unable to read letters on a testing chart, visual acuity is described as ranging from ability to count fingers, recognize hand movements, or light perception. The smaller BVCA score indicates greater severity of uveitis. A positive change from best state value obtained prior to Week 6 indicates improvement.	Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks)
Log Change in Central Retinal Thickness in Each Eye, From Best State Achieved Prior to Week 6 to Week 52 or EOT Visit or ET	Central retinal thickness is measured by optical coherence tomography (OCT). Central retinal thickness is defined as the thickness of the retina in the center of the foveal pit (1 mm subfield). The larger central retinal thickness value indicates greater severity of uveitis. A negative change from best state value obtained prior to Week 6 indicates improvement.	Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks)
Time to Development of Macular Edema in At Least One Eye on or After Week 6	Time in weeks until the development of Macular edema or Week 52 or EOT or ET. Macular edema is determined by OCT and is defined as central retinal thickness ≥ 300 microns if using Cirrus machine, or ≥ 315 microns if using Spectralis machine.	Week 6 through Week 52
Plasma Concentration of Filgotinib		Day 1 post dose, Weeks 4 and 6 predose, Week 12 post dose, Weeks 24, 36, 52 (EOT), ET at any time
Plasma Concentration of Metabolite, GS-829845		Day 1 post dose, Weeks 4 and 6 predose, Week 12 post dose, Weeks 24, 36, 52 (EOT), ET at any time

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Collaborators: Galapagos NV

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2017
• Primary Completion (Actual): December 29, 2020
• Study Completion (Actual): April 22, 2021

Study Registration Dates

• First Submitted: June 30, 2017
• First Submitted That Met QC Criteria: June 30, 2017
• First Posted (Actual): July 5, 2017

Study Record Updates

• Last Update Posted (Actual): January 21, 2022
• Last Update Submitted That Met QC Criteria: December 23, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Uveal Diseases; Uveitis; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: GS-US-432-4097; 2017-001485-17 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No