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

NCT03207815 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: GS-US-432-40972017-001485-17
• Study Type: interventional
• Target: 74
• Locations: 7 countries
• Sites: 24

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.

Conditions

Noninfectious Uveitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Time to Treatment Failure on or After Week 6

  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)

  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

  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

  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

  Prior to Week 6; Up to Week 52 or EOT or ET (maximum: 53 weeks)

Study Arms (2)

Filgotinib

EXPERIMENTAL

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; Drug: Prednisone

Placebo

PLACEBO COMPARATOR

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: Placebo to match filgotinib; Drug: Prednisone

Interventions

Filgotinib DRUG

Tablet(s) administered orally

Also known as: GS-6034, GLPG0634

Filgotinib

Placebo to match filgotinib DRUG

Tablet(s) administered orally

Placebo

Prednisone DRUG

Tablet(s) administered orally

Filgotinib; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Gilead Sciences: lead
• Galapagos NV: collaborator

Study Sites (24)

Stanford Byers Eye Institute

Palo Alto, California, 94303, United States

Location

Colorado Retina Associates PC

Golden, Colorado, 80401, United States

Location

Northwestern Medical Group

Chicago, Illinois, 60611, United States

Location

Illinois Retina Associates

Oak Park, Illinois, 60304, United States

Location

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

Location

Associated Retinal Consultants PC

Royal Oak, Michigan, 48073, United States

Location

Metropolitan Eye Research and Surgery Institute

Palisades Park, New Jersey, 07650, United States

Location

Duke University Eye Center

Durham, North Carolina, 27710, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic Foundation-Cole Eye Institute

Cleveland, Ohio, 44191, United States

Location

Oregon Health Science University-Casey Eye Institute

Portland, Oregon, 97239, United States

Location

Mid Atlantic Retina

Philadelphia, Pennsylvania, 19107, United States

Location

Texas Retina Associates - Fort Worth

Fort Worth, Texas, 76104, United States

Location

Foresight Studies, LLC

San Antonio, Texas, 78240, United States

Location

university of Wisconsin-Madison

Madison, Wisconsin, 53705, United States

Location

Lions Eye Institute

Nedlands, Western Australia, 6009, Australia

Location

Retina Consultants

Vancouver, V5Z 0E9, Canada

Location

St. Franziskus Hospital

Münster, Germany

Location

Hadassah Medical Center

Jerusalem, 91120, Israel

Location

Auckland Eye

Remuera, 1050, New Zealand

Location

Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

Moorfields Eye Hospital NHS Foundation Trust

London, United Kingdom

Location

Central Mancester Hospitals NHS Foundation Trust, Manchester Royal Eye Hospital

Manchester, M13 9WL, United Kingdom

Location

Eye Research Group Oxford, Oxford Eye Hospital

Oxford, OX3 9DU, United Kingdom

Location

Related Publications (2)

• Srivastava SK, Watkins TR, Nguyen QD, Sharma S, Scales DK, Dacey MS, Shah RE, Chu DS, Grewal DS, Faia LJ, Suhler EB, Genovese MC, Guo Y, Barchuk WT, Besuyen R, Dick AD, Rosenbaum JT. Filgotinib in Active Noninfectious Uveitis: The HUMBOLDT Randomized Clinical Trial. JAMA Ophthalmol. 2024 Sep 1;142(9):789-797. doi: 10.1001/jamaophthalmol.2024.2439.

  PMID: 39023880 DERIVED

• Hashida N, Nishida K. Recent advances and future prospects: Current status and challenges of the intraocular injection of drugs for vitreoretinal diseases. Adv Drug Deliv Rev. 2023 Jul;198:114870. doi: 10.1016/j.addr.2023.114870. Epub 2023 May 10.

  PMID: 37172783 DERIVED

MeSH Terms

Interventions

GLPG0634; Prednisone

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

Study was terminated early due to termination of the development program. Due to early termination and small sample size, pharmacokinetic (PK) analysis was not performed for this study.

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2017
• First Posted: July 5, 2017
• Study Start: July 26, 2017
• Primary Completion: December 29, 2020
• Study Completion: April 22, 2021
• Last Updated: January 21, 2022
• Results First Posted: January 21, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (15); IL (1); AU (1); CA (1); GB (4); NZ (1); DE (1)