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

Primary Purpose

Noninfectious Uveitis

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Filgotinib
Placebo to match filgotinib
Prednisone
Sponsored by
Gilead Sciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Noninfectious Uveitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Stanford Byers Eye Institute
  • Colorado Retina Associates PC
  • Northwestern Medical Group
  • Illinois Retina Associates
  • Ophthalmic Consultants of Boston
  • Associated Retinal Consultants PC
  • Metropolitan Eye Research and Surgery Institute
  • Duke University Eye Center
  • Wake Forest Baptist Medical Center
  • Cleveland Clinic Foundation-Cole Eye Institute
  • Oregon Health Science University-Casey Eye Institute
  • Mid Atlantic Retina
  • Texas Retina Associates - Fort Worth
  • Foresight Studies, LLC
  • university of Wisconsin-Madison
  • Lions Eye Institute
  • Retina Consultants
  • St. Franziskus Hospital
  • Hadassah Medical Center
  • Auckland Eye
  • Royal Liverpool University Hospital
  • Moorfields Eye Hospital NHS Foundation Trust
  • Central Mancester Hospitals NHS Foundation Trust, Manchester Royal Eye Hospital
  • Eye Research Group Oxford, Oxford Eye Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Filgotinib

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
Plasma Concentration of Filgotinib
Plasma Concentration of Metabolite, GS-829845

Full Information

First Posted
June 30, 2017
Last Updated
December 23, 2021
Sponsor
Gilead Sciences
Collaborators
Galapagos NV
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1. Study Identification

Unique Protocol Identification Number
NCT03207815
Brief Title
Study to Evaluate the Efficacy and Safety of Filgotinib in Adults With Active Noninfectious Uveitis
Acronym
HUMBOLDT
Official Title
A Phase 2, Randomized, Placebo-Controlled Trial Evaluating the Efficacy and Safety of Filgotinib in Subjects With Active Noninfectious Uveitis
Study Type
Interventional

2. Study Status

Record Verification Date
December 2021
Overall Recruitment Status
Terminated
Why Stopped
Development program terminated
Study Start Date
July 26, 2017 (Actual)
Primary Completion Date
December 29, 2020 (Actual)
Study Completion Date
April 22, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
Collaborators
Galapagos NV

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Noninfectious Uveitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
74 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Filgotinib
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Filgotinib
Other Intervention Name(s)
GS-6034, GLPG0634
Intervention Description
Tablet(s) administered orally
Intervention Type
Drug
Intervention Name(s)
Placebo to match filgotinib
Intervention Description
Tablet(s) administered orally
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Tablet(s) administered orally
Primary Outcome Measure Information:
Title
Percentage of Participants Failing Treatment for Active NonInfectious Uveitis by Week 24
Description
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.
Time Frame
Week 6 through Week 24
Secondary Outcome Measure Information:
Title
Time to Treatment Failure on or After Week 6
Description
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.
Time Frame
Week 6 through Week 52
Title
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)
Description
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.
Time Frame
Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks)
Title
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
Description
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.
Time Frame
Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks)
Title
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
Description
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.
Time Frame
Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks)
Title
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
Description
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.
Time Frame
Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks)
Title
Time to Development of Macular Edema in At Least One Eye on or After Week 6
Description
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.
Time Frame
Week 6 through Week 52
Title
Plasma Concentration of Filgotinib
Time Frame
Day 1 post dose, Weeks 4 and 6 predose, Week 12 post dose, Weeks 24, 36, 52 (EOT), ET at any time
Title
Plasma Concentration of Metabolite, GS-829845
Time Frame
Day 1 post dose, Weeks 4 and 6 predose, Week 12 post dose, Weeks 24, 36, 52 (EOT), ET at any time

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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) 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Stanford Byers Eye Institute
City
Palo Alto
State/Province
California
ZIP/Postal Code
94303
Country
United States
Facility Name
Colorado Retina Associates PC
City
Golden
State/Province
Colorado
ZIP/Postal Code
80401
Country
United States
Facility Name
Northwestern Medical Group
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Illinois Retina Associates
City
Oak Park
State/Province
Illinois
ZIP/Postal Code
60304
Country
United States
Facility Name
Ophthalmic Consultants of Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Associated Retinal Consultants PC
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
Metropolitan Eye Research and Surgery Institute
City
Palisades Park
State/Province
New Jersey
ZIP/Postal Code
07650
Country
United States
Facility Name
Duke University Eye Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Wake Forest Baptist Medical Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Cleveland Clinic Foundation-Cole Eye Institute
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44191
Country
United States
Facility Name
Oregon Health Science University-Casey Eye Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Mid Atlantic Retina
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Texas Retina Associates - Fort Worth
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Foresight Studies, LLC
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78240
Country
United States
Facility Name
university of Wisconsin-Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53705
Country
United States
Facility Name
Lions Eye Institute
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Retina Consultants
City
Vancouver
ZIP/Postal Code
V5Z 0E9
Country
Canada
Facility Name
St. Franziskus Hospital
City
Münster
Country
Germany
Facility Name
Hadassah Medical Center
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Auckland Eye
City
Remuera
ZIP/Postal Code
1050
Country
New Zealand
Facility Name
Royal Liverpool University Hospital
City
Liverpool
ZIP/Postal Code
L7 8XP
Country
United Kingdom
Facility Name
Moorfields Eye Hospital NHS Foundation Trust
City
London
Country
United Kingdom
Facility Name
Central Mancester Hospitals NHS Foundation Trust, Manchester Royal Eye Hospital
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
Facility Name
Eye Research Group Oxford, Oxford Eye Hospital
City
Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

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

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