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Ustekinumab for Active Sight-Threatening Uveitis

Primary Purpose

Uveitis

Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Ustekinumab
Sponsored by
National Eye Institute (NEI)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Uveitis focused on measuring Uveitis, Ustekinumab, IL 12/23, Stelara

Eligibility Criteria

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

  • INCLUSION CRITERIA:

    1. Participant has the ability to understand and sign the informed consent document.
    2. Participant is 18 years of age or older.
    3. Participant has negative PPD or quantiferon testing done within three months prior to enrollment or had latent TB but has completed prophylactic anti-TB treatment.

    4. Participant has active intermediate uveitis, posterior uveitis or panuveitis in at least one eye requiring systemic therapy. Active disease is defined as:

      • 1 or more anterior chamber cells (according to SUN criteria); and/or
      • 0.5 or more vitreous haze (according to SUN criteria); and/or

      Active chorioretinitis or greater than or equal to quadrants with leakage on FA.

    5. Participant has visual acuity in at least one eye of 20/400 or better.
    6. Participant is willing and able to comply with the study procedures.
    7. Female participants of childbearing potential must not be pregnant or breast-feeding, have a negative pregnancy test at screening and must be willing to undergo pregnancy testing throughout the study.
    8. Both female participants of childbearing potential and male participants able to father a child must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice two effective methods of contraception throughout the course of the study and for six weeks after the last investigational product injection. Acceptable methods of contraception for this study include:
  • hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring),
  • intrauterine device,
  • barrier methods (diaphragm, condom) with spermicide, or
  • surgical sterilization (tubal ligation).

EXCLUSION CRITERIA:

  1. Participant has a significant active infection (an infection requiring treatment as determined by the medical team), including active tuberculosis or human immunodeficiency virus (HIV).
  2. Participant received a live vaccination within the past six weeks.
  3. Participant is expected to receive a live vaccination at any time during the study.
  4. Participant received the Bacillus Calmette-Guerin (BCG) vaccine within the past year.
  5. Participant is expected to receive the BCG vaccine at anytime during the study or up to one year after discontinuing ustekinumab.
  6. Participant has a history of cancer (other than a non-melanoma skin cancer) diagnosed within the past five years.
  7. Participant has received intraocular (or periocular) steroid or anti-VEGF injections within the last six weeks.

Sites / Locations

    Outcomes

    Primary Outcome Measures

    The primary outcome is the number of participants who experience at least a 2-step (or down to grade 0) reduction in inflammation as per the Standardization of Uveitis Nomenclature (SUN) criteria by Week 8.

    Secondary Outcome Measures

    Full Information

    First Posted
    July 19, 2012
    Last Updated
    December 4, 2019
    Sponsor
    National Eye Institute (NEI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01647152
    Brief Title
    Ustekinumab for Active Sight-Threatening Uveitis
    Official Title
    A Pilot Study to Investigate Ustekinumab (StelaraTM) for the Treatment of Active Sight-Threatening Uveitis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 5, 2014
    Overall Recruitment Status
    Withdrawn
    Study Start Date
    July 3, 2012 (undefined)
    Primary Completion Date
    June 30, 2015 (Anticipated)
    Study Completion Date
    June 30, 2015 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    National Eye Institute (NEI)

    4. Oversight

    5. Study Description

    Brief Summary
    Background: - Uveitis is an eye inflammation that can cause vision loss. It is treated with eye drops, drugs and sometimes surgery. In some people, treatment may not prevent vision loss. A type of white blood cells called T-cells often have a role in causing uveitis. In some cases of uveitis, T-cells attack the eye and cause inflammation. A drug called ustekinumab reduces inflammation from these T-cells. Researchers want to see if ustekinumab can be used to treat uveitis. Objectives: - To see if ustekinumab can be used to treat uveitis. Eligibility: - Individuals at least 18 years of age who have active uveitis that needs treatment. Design: Participants will be screened with a physical exam, eye exam, and medical history. Blood and urine samples will be taken. Participants will have at least eight clinic visits during the 64-week study period. After the first visit, visits will occur at 2, 4, and 8 weeks, and then every 12 weeks. Participants will have a ustekinumab injection at the first study visit. They will have additional doses at the second and third visits, and then every 12 weeks until 1 year after the first dose (Week 52). Treatment will be monitored with frequent blood tests and eye exams. Other standard treatments for uveitis may be given as needed. There will be a final study visit 3 months after the last injection.
    Detailed Description
    Objective: Uveitis refers to intraocular inflammatory diseases that are an important cause of visual loss. Standard systemic immunosuppressive medications for uveitis can cause significant adverse effects and many patients continue to experience disease flare-ups. Ustekinumab is a human IL-12 and -23 antagonist. The involvement of IL-12 and IL-23 in the pathophysiology of uveitis and other autoimmune diseases known to be associated with uveitis suggests that ustekinumab could be a potential treatment for uveitis. The study objective is to investigate the safety, tolerability and potential efficacy of subcutaneous injections of ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis. Study Population: Five participants with active intermediate uveitis, posterior uveitis or panuveitis who meet the inclusion criteria will be initially enrolled. Up to seven participants may be enrolled, as up to two participants may be accrued to account for participants who withdraw from the study prior to Week 8. Design: This is a prospective, non-randomized, uncontrolled, single-center pilot study to evaluate subcutaneous injections of ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis. Participants will receive a 90 mg subcutaneous injection of ustekinumab at baseline and a second and third injection at Week 2 and 4 and every 12 weeks thereafter. Participants will continue to receive injections of ustekinumab every 12 weeks until Week 52. Participants will return for a final safety visit 12 weeks later. Outcome Measures: The primary outcome is the number of participants who experience treatment response (as defined in Appendix 1) by Week 8. Secondary outcomes include changes in visual acuity, the number of participants who experience a recurrence, the number of days to recurrence, presence or extent of macular edema, the amount of retino-vascular leakage, changes in retinal thickening, the length of time to quiescence and the ability to taper concomitant immunosuppressive medications. Safety outcomes include the number and severity of systemic and ocular toxicities and adverse events, the proportion of participants who experience vision loss of greater than or equal to 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and the number of participants who experience a substantial rise in elevated intraocular pressure (IOP).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Uveitis
    Keywords
    Uveitis, Ustekinumab, IL 12/23, Stelara

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Intervention Type
    Drug
    Intervention Name(s)
    Ustekinumab
    Primary Outcome Measure Information:
    Title
    The primary outcome is the number of participants who experience at least a 2-step (or down to grade 0) reduction in inflammation as per the Standardization of Uveitis Nomenclature (SUN) criteria by Week 8.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    INCLUSION CRITERIA: Participant has the ability to understand and sign the informed consent document. Participant is 18 years of age or older. Participant has negative PPD or quantiferon testing done within three months prior to enrollment or had latent TB but has completed prophylactic anti-TB treatment. Participant has active intermediate uveitis, posterior uveitis or panuveitis in at least one eye requiring systemic therapy. Active disease is defined as: 1 or more anterior chamber cells (according to SUN criteria); and/or 0.5 or more vitreous haze (according to SUN criteria); and/or Active chorioretinitis or greater than or equal to quadrants with leakage on FA. Participant has visual acuity in at least one eye of 20/400 or better. Participant is willing and able to comply with the study procedures. Female participants of childbearing potential must not be pregnant or breast-feeding, have a negative pregnancy test at screening and must be willing to undergo pregnancy testing throughout the study. Both female participants of childbearing potential and male participants able to father a child must have (or have a partner who has) had a hysterectomy or vasectomy, be completely abstinent from intercourse or must agree to practice two effective methods of contraception throughout the course of the study and for six weeks after the last investigational product injection. Acceptable methods of contraception for this study include: hormonal contraception (i.e., birth control pills, injected hormones, dermal patch or vaginal ring), intrauterine device, barrier methods (diaphragm, condom) with spermicide, or surgical sterilization (tubal ligation). EXCLUSION CRITERIA: Participant has a significant active infection (an infection requiring treatment as determined by the medical team), including active tuberculosis or human immunodeficiency virus (HIV). Participant received a live vaccination within the past six weeks. Participant is expected to receive a live vaccination at any time during the study. Participant received the Bacillus Calmette-Guerin (BCG) vaccine within the past year. Participant is expected to receive the BCG vaccine at anytime during the study or up to one year after discontinuing ustekinumab. Participant has a history of cancer (other than a non-melanoma skin cancer) diagnosed within the past five years. Participant has received intraocular (or periocular) steroid or anti-VEGF injections within the last six weeks.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Hatice N Sen, M.D.
    Organizational Affiliation
    National Eye Institute (NEI)
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    15019324
    Citation
    Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology. 2004 Mar;111(3):491-500; discussion 500. doi: 10.1016/j.ophtha.2003.06.014.
    Results Reference
    background
    PubMed Identifier
    12434489
    Citation
    Djalilian AR, Nussenblatt RB. Immunosuppression in uveitis. Ophthalmol Clin North Am. 2002 Sep;15(3):395-404, viii. doi: 10.1016/s0896-1549(02)00036-6.
    Results Reference
    background
    PubMed Identifier
    18391061
    Citation
    Luger D, Silver PB, Tang J, Cua D, Chen Z, Iwakura Y, Bowman EP, Sgambellone NM, Chan CC, Caspi RR. Either a Th17 or a Th1 effector response can drive autoimmunity: conditions of disease induction affect dominant effector category. J Exp Med. 2008 Apr 14;205(4):799-810. doi: 10.1084/jem.20071258. Epub 2008 Apr 7.
    Results Reference
    background

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    Ustekinumab for Active Sight-Threatening Uveitis

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