Adalimumab in JIA-associated Uveitis Stopping Trial (ADJUST)

March 5, 2024 updated by: Nisha Acharya

Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial

The proposed study is a stratified, block-randomized, double-masked, controlled trial to determine the feasibility of discontinuing adalimumab treatment in patients with quiescent uveitis associated with juvenile idiopathic arthritis (JIA) or chronic anterior uveitis (CAU).

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Background: Juvenile idiopathic arthritis (JIA)-associated uveitis is a chronic pediatric ocular inflammatory condition that can result in visual impairment. Chronic anterior uveitis (CAU) does not have systemic manifestations of disease but presents similarly in the eye and can result in identical visual complications as JIA-associated uveitis. Adalimumab, a tumor necrosis factor (TNF)-alpha inhibitor, effectively controls joint and eye inflammation; however, its long-term use may increase the risk of adverse health outcomes and place an undue financial burden on the patient and healthcare system given its high cost. There is great interest for patients to stop adalimumab following remission due to these reasons but there is a lack of information on the ability to maintain control after discontinuing adalimumab.

Methods: The Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Trial (ADJUST) is a multi-center international trial that will randomize 118 participants aged 2 years and older with controlled JIA-associated uveitis or chronic anterior uveitis to either continue adalimumab or discontinue adalimumab and receive a placebo. The trial will compare the time to uveitis recurrence between the two groups over 12 months. All participants will receive the standard weight-based dose of adalimumab or placebo: 20 mg biweekly (if < 30 kg) or 40 mg biweekly (if ≥ 30 kg).

Impact: This is the first randomized controlled trial to assess the efficacy of discontinuing adalimumab after demonstrating control of JIA-associated uveitis for at least 12 months. The results of ADJUST will provide information on clinical outcomes to guide clinicians in their decision-making regarding discontinuation of adalimumab.

Study Type

Interventional

Enrollment (Estimated)

118

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • Victoria
      • Parkville, Victoria, Australia, 3052
        • Murdoch Children's Research Institute
  • United Kingdom
      • Bristol, United Kingdom, BS1 3NU
        • University Hospitals Bristol and Weston
      • Cambridge, United Kingdom
        • Cambridge university hospital
      • Leicester, United Kingdom
        • University Hospitals, Leicester
      • Liverpool, United Kingdom, L14 5AB
        • Alder Hey Children's Hospital
      • London, United Kingdom, WC1N 3JH
        • Great Ormond Street Hospital
      • Manchester, United Kingdom
        • Manchester University NHS Foundation Trust
      • Newcastle Upon Tyne, United Kingdom, NE1 4LP
        • Great North Children's Hospital
      • Norwich, United Kingdom, NR4 6TZ
        • Norfolk and Norwich University Hospital
      • Sheffield, United Kingdom, S10 2TQ
        • Sheffield Children's Hospital
  • United States
    • California
      • Sacramento, California, United States, 95817
        • University of California, Davis
      • San Francisco, California, United States, 94143
        • University of California, San Francisco
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Denver
      • Lakewood, Colorado, United States, 80228
        • Colorado Retina Associates
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
    • Tennessee
      • Nashville, Tennessee, United States, 37212
        • Vanderbilt University Medical Center
    • Texas
      • Austin, Texas, United States, 78712
        • University of Texas, Austin
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria (must meet all of the following to qualify):

  • Stated willingness to comply with all study procedures and availability for the duration of the study period
  • ≥ 2 years of age
  • History of JIA or CAU diagnosed prior to 16 years of age (patient may be older than 16 at time of enrollment)
  • Formal diagnosis of JIA-associated uveitis or CAU with no other suspected etiology
  • ≥12 consecutive months of controlled ocular inflammation (≤0.5+ anterior chamber cell, ≤0.5+ vitreous haze, no active retinal/choroidal lesions in either eye)
  • ≥ 12 consecutive months of controlled arthritis verified by a pediatric rheumatologist, if defined as JIA-associated uveitis
  • ≥12 consecutive months of treatment with adalimumab or a biosimilar of adalimumab
  • ≥180 days on a stable dose of adalimumab or a biosimilar; must be biweekly dose of either 20mg (if<30kg) or 40mg (if ≥30kg)
  • If on a biosimilar of adalimumab, ≥90 days on the biosimilar
  • If on concomitant antimetabolite (injectable or oral methotrexate, mycophenolate mofetil, azathioprine, or leflunomide), dose must be ≤25 mg weekly for methotrexate, ≤3 g daily for mycophenolate mofetil, ≤250 mg daily for azathioprine, or ≤20 mg daily for leflunomide; dose and route of administration must be stable for ≥90 days
  • If on topical corticosteroids, dose must be ≤2 drops prednisolone acetate 1% or equivalent per day and stable for ≥90 days
  • Willingness to limit consumption of alcohol during the study period
  • Agreement to avoid live attenuated vaccinations
  • Agreement to use highly effective contraception for ≥28 days prior to screening and throughout study period (for males and females of reproductive age)
  • Suitable, in the opinion of the Investigator, to continue treatment with adalimumab or placebo per regional labeling
  • No contraindications to receive adalimumab as per the local Summary of Product Characteristics (SmPC)

Exclusion Criteria (any one of these excludes the patient):

  • Intraocular surgery in the past 90 days or planned surgery in the next 12 months
  • Severe cataract or opacity preventing view to the posterior pole in both eyes
  • Chronic hypotony (<5mmHg for ≥90 days) in either eye
  • Treatment with oral corticosteroids or intraocular corticosteroid injection within the last 12 months
  • Use of NSAID eye drops within the last 90 days
  • Acute anterior uveitis characterized by redness and symptoms, including but not limited to floaters, pain, and light sensitivity
  • Pregnancy or lactation (a pregnancy test will be conducted at baseline and all follow-up visits for females of reproductive age)
  • Presence of intraretinal or subretinal fluid in either eye
  • Prior safety or tolerability issues with adalimumab
  • History of cancer, active tuberculosis, or hepatitis B
  • Other medical condition expected to dictate treatment course during the study
  • Any of the following laboratory test results on their most recent tests within the past 90 days prior to screening/enrollment: leukocyte count <2500, platelet count ≤75000, hemoglobin<9.0, AST or ALT ≥ 2 times the upper limit of normal range, creatinine ≥1.5

There are no sex, race, or ethnicity restrictions for this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Continue adalimumab
Patients randomized to this arm will continue adalimumab at their current dose (either 20mg/0.2mL or 40mg/0.4mL) administered subcutaneously every other week.
Biological: Adalimumab
Adalimumab is a fully human monoclonal anti-tumor necrosis factor alpha antibody, a biologic, immunomodulatory drug. Adalimumab 20mg/0.8mL and 40mg/0.8mL is a clear, colorless solution provided in a pre-filled syringe for subcutaneous injection. The formulation is adalimumab, mannitol, polysorbate 80, and water for injection Each pre-filled syringe has a fixed 29-gauge thin wall and ½ inch needle with black protective cover and is intended for a single dose to a single patient.
Other Names:
  • HUMIRA
Placebo Comparator: Stop adalimumab
Patients randomized to this arm will receive a volume-matched placebo (0.8mL) administered subcutaneously every other week.
Other: Placebo
The placebo solution is a clear, colorless solution provided in a single-use, pre-filled syringe for subcutaneous injection. The placebo is designed to match the characteristics of the citrate-free adalimumab during injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to treatment failure
Time Frame: From baseline until 12 months post-randomization

Time to treatment failure until 12 months post-randomization. Treatment failure is defined by recurrence of ocular inflammation in at least one eye as follows:

  • 3+ anterior chamber (AC) for a single visit

    •>0.5+ anterior chamber (AC) cell for ≥28 days

  • 2-step increase in AC cell observed at two separate visits ≥7 days apart

    • 0.5+ vitreous haze, active retinal or choroidal inflammation, or macular edema observed at a single visit. Treatment failure can also be declared by recurrence of joint inflammation that is persistent and severe enough to necessitate unmasking to manage the arthritis recurrence.
From baseline until 12 months post-randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nisha Acharya

Collaborators

Children's Hospital of Philadelphia
University of Miami
National Eye Institute (NEI)
University of California, Davis
Cambridge University Hospitals NHS Foundation Trust
Norfolk and Norwich University Hospitals NHS Foundation Trust
Vanderbilt University Medical Center
Children's Hospital Medical Center, Cincinnati
University of Utah
University Hospitals, Leicester
Manchester University NHS Foundation Trust
Children's Mercy Hospital Kansas City
Royal Children's Hospital
Newcastle-upon-Tyne Hospitals NHS Trust
University Hospitals Bristol and Weston NHS Foundation Trust
University of Texas at Austin
Great Ormond Street Hospital for Children NHS Foundation Trust
Alder Hey Children's NHS Foundation Trust
Sheffield Children's NHS Foundation Trust
Colorado Retina Associates

Investigators

  • Principal Investigator: Nisha Acharya, MD MS, Principal Investigator

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2020

Primary Completion (Estimated)

April 30, 2025

Study Completion (Estimated)

July 30, 2025

Study Registration Dates

First Submitted

January 22, 2019

First Submitted That Met QC Criteria

January 22, 2019

First Posted (Actual)

January 25, 2019

Study Record Updates

Last Update Posted (Actual)

March 7, 2024

Last Update Submitted That Met QC Criteria

March 5, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-23987
  • UG1EY029658 (U.S. NIH Grant/Contract)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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