Adalimumab in JIA-associated Uveitis Stopping Trial

Study Purpose

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).

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 2 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03816397
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 4
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Nisha Acharya
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Nisha Acharya, MD MS
Principal Investigator Affiliation Principal Investigator
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, NIH
Overall Status Recruiting
Countries Australia, United Kingdom, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Uveitis, JIA
Additional Details

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.

Arms & Interventions

Arms

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.

Placebo Comparator: Stop adalimumab

Patients randomized to this arm will receive a volume-matched placebo (0.8mL) administered subcutaneously every other week.

Interventions

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: - 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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of California, Davis, Sacramento, California

Status

Recruiting

Address

University of California, Davis

Sacramento, California, 95817

Site Contact

Parisa Emami-Naeini, MD, MPH

[email protected]

415-476-8131

University of California, San Francisco, San Francisco, California

Status

Recruiting

Address

University of California, San Francisco

San Francisco, California, 94143

Site Contact

Nisha Acharya, MD MS

[email protected]

415-476-8131

University of Colorado Denver, Aurora, Colorado

Status

Recruiting

Address

University of Colorado Denver

Aurora, Colorado, 80045

Site Contact

Katharine Moore, MD

[email protected]

415-476-8131

Colorado Retina Associates, Lakewood, Colorado

Status

Recruiting

Address

Colorado Retina Associates

Lakewood, Colorado, 80228

Site Contact

Mark Dacey, MD

[email protected]

415-476-8131

University of Miami, Miami, Florida

Status

Recruiting

Address

University of Miami

Miami, Florida, 33136

Site Contact

Janet L Davis, MD

[email protected]

415-476-8131

Children's Mercy Hospital, Kansas City, Missouri

Status

Recruiting

Address

Children's Mercy Hospital

Kansas City, Missouri, 64108

Site Contact

Erin Stahl, MD

[email protected]

415-476-8131

Cincinnati Children's Hospital, Cincinnati, Ohio

Status

Recruiting

Address

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229

Site Contact

Virginia Miraldi Utz, MD

[email protected]

415-476-8131

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

Status

Recruiting

Address

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104

Site Contact

Stefanie Davidson, MD

[email protected]

415-476-8131

Vanderbilt University Medical Center, Nashville, Tennessee

Status

Recruiting

Address

Vanderbilt University Medical Center

Nashville, Tennessee, 37212

Site Contact

Sapna Gangaputra, MD, MPH

[email protected]

415-476-8131

University of Texas, Austin, Austin, Texas

Status

Recruiting

Address

University of Texas, Austin

Austin, Texas, 78712

Site Contact

Eric Crowell, MD, MPH

[email protected]

415-476-8131

University of Utah Health, Salt Lake City, Utah

Status

Recruiting

Address

University of Utah Health

Salt Lake City, Utah, 84132

Site Contact

Albert Vitale, MD

[email protected]

415-476-8131

International Sites

Murdoch Children's Research Institute, Parkville, Victoria, Australia

Status

Recruiting

Address

Murdoch Children's Research Institute

Parkville, Victoria, 3052

Site Contact

William Renton

[email protected]

+61 03 9345 5522

University Hospitals Bristol and Weston, Bristol, United Kingdom

Status

Recruiting

Address

University Hospitals Bristol and Weston

Bristol, , BS1 3NU

Site Contact

A V Ramanan

[email protected]

415-476-8131

Cambridge University Hospital, Cambridge, United Kingdom

Status

Recruiting

Address

Cambridge University Hospital

Cambridge, ,

University Hospitals, Leicester, Leicester, United Kingdom

Status

Recruiting

Address

University Hospitals, Leicester

Leicester, ,

Site Contact

Arani Sridhar, MD

[email protected]

415-476-8131

Alder Hey Children's Hospital, Liverpool, United Kingdom

Status

Recruiting

Address

Alder Hey Children's Hospital

Liverpool, , L14 5AB

Site Contact

Jose Gonzalez-Martin

[email protected]

415-476-8131

Great Ormond Street Hospital, London, United Kingdom

Status

Recruiting

Address

Great Ormond Street Hospital

London, , WC1N 3JH

Site Contact

Elena Moraitis

[email protected]

415-476-8131

Manchester, United Kingdom

Status

Recruiting

Address

Manchester University NHS Foundation Trust

Manchester, ,

Site Contact

Jane Ashworth, MD

[email protected]

415-476-8131

Great North Children's Hospital, Newcastle Upon Tyne, United Kingdom

Status

Recruiting

Address

Great North Children's Hospital

Newcastle Upon Tyne, , NE1 4LP

Site Contact

Michael Clarke

[email protected]

415-476-8131

Norfolk and Norwich University Hospital, Norwich, United Kingdom

Status

Recruiting

Address

Norfolk and Norwich University Hospital

Norwich, , NR4 6TZ

Site Contact

Narman Puvanachandra

[email protected]

415-476-8131

Sheffield Children's Hospital, Sheffield, United Kingdom

Status

Recruiting

Address

Sheffield Children's Hospital

Sheffield, , S10 2TQ

Site Contact

Jessy Choi

[email protected]

415-476-8131