Adalimumab in JIA-associated Uveitis Stopping Trial

NCT03816397 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: 17-23987UG1EY029658
• Study Type: interventional
• Target: 87
• Locations: 3 countries
• Sites: 21

Brief Summary

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).

Conditions

Uveitis; JIA

Keywords

chronic anterior uveitis; adalimumab; JIA-associated uveitis; stopping

Outcome Measures

Primary Outcomes (1)

• Time to Treatment Failure

  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. Time (days) from all participants is included in the analysis.

  From baseline until 48 weeks post-randomization

Study Arms (2)

Continue adalimumab

ACTIVE COMPARATOR

Patients randomized to this arm will continue adalimumab at their current weight-based dose administered subcutaneously every other week.

Biological: Adalimumab

Stop adalimumab

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Adalimumab BIOLOGICAL

Adalimumab is a fully human monoclonal anti-tumor necrosis factor alpha antibody, a biologic, immunomodulatory drug. Adalimumab 20mg/0.8 mL and 40mg/0.8 mL 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.

Also known as: HUMIRA

Continue adalimumab

Placebo OTHER

The placebo solution is a clear, colorless solution provided in a single-use, pre-filled syringe for subcutaneous injection. The volume-matched (0.8mL) placebo is designed to match the characteristics of the citrate-free adalimumab during injection.

Stop adalimumab

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 (\<5 mmHg 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, Aspartate Aminotransferase (AST) or Alanine Transferase (ALT) ≥ 2 times the upper limit of normal range, creatinine ≥1.5
• There are no sex, race, or ethnicity restrictions for this study.

Sponsors & Collaborators

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

Study Sites (21)

University of California, Davis

Sacramento, California, 95817, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Colorado Retina Associates

Lakewood, Colorado, 80228, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

University of Texas, Austin

Austin, Texas, 78712, United States

Location

University of Utah Health

Salt Lake City, Utah, 84132, United States

Location

Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

Location

University Hospitals Bristol and Weston

Bristol, BS1 3NU, United Kingdom

Location

Cambridge University Hospital

Cambridge, United Kingdom

Location

University Hospitals, Leicester

Leicester, United Kingdom

Location

Alder Hey Children's Hospital

Liverpool, L14 5AB, United Kingdom

Location

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

Location

Manchester University NHS Foundation Trust

Manchester, United Kingdom

Location

Great North Children's Hospital

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Norfolk and Norwich University Hospital

Norwich, NR4 6TZ, United Kingdom

Location

Sheffield Children's Hospital

Sheffield, S10 2TQ, United Kingdom

Location

Related Publications (9)

• Jaffe GJ, Dick AD, Brezin AP, Nguyen QD, Thorne JE, Kestelyn P, Barisani-Asenbauer T, Franco P, Heiligenhaus A, Scales D, Chu DS, Camez A, Kwatra NV, Song AP, Kron M, Tari S, Suhler EB. Adalimumab in Patients with Active Noninfectious Uveitis. N Engl J Med. 2016 Sep 8;375(10):932-43. doi: 10.1056/NEJMoa1509852.

  PMID: 27602665 BACKGROUND

• Nguyen QD, Merrill PT, Jaffe GJ, Dick AD, Kurup SK, Sheppard J, Schlaen A, Pavesio C, Cimino L, Van Calster J, Camez AA, Kwatra NV, Song AP, Kron M, Tari S, Brezin AP. Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet. 2016 Sep 17;388(10050):1183-92. doi: 10.1016/S0140-6736(16)31339-3. Epub 2016 Aug 16.

  PMID: 27542302 BACKGROUND

• Ramanan AV, Dick AD, Benton D, Compeyrot-Lacassagne S, Dawoud D, Hardwick B, Hickey H, Hughes D, Jones A, Woo P, Edelsten C, Beresford MW; SYCAMORE Trial Management Group. A randomised controlled trial of the clinical effectiveness, safety and cost-effectiveness of adalimumab in combination with methotrexate for the treatment of juvenile idiopathic arthritis associated uveitis (SYCAMORE Trial). Trials. 2014 Jan 9;15:14. doi: 10.1186/1745-6215-15-14.

  PMID: 24405833 BACKGROUND

• Vazquez-Cobian LB, Flynn T, Lehman TJ. Adalimumab therapy for childhood uveitis. J Pediatr. 2006 Oct;149(4):572-5. doi: 10.1016/j.jpeds.2006.04.058.

  PMID: 17011337 BACKGROUND

• Chang CY, Meyer RM, Reiff AO. Impact of medication withdrawal method on flare-free survival in patients with juvenile idiopathic arthritis on combination therapy. Arthritis Care Res (Hoboken). 2015 May;67(5):658-66. doi: 10.1002/acr.22477.

  PMID: 25220674 BACKGROUND

• Baszis K, Garbutt J, Toib D, Mao J, King A, White A, French A. Clinical outcomes after withdrawal of anti-tumor necrosis factor alpha therapy in patients with juvenile idiopathic arthritis: a twelve-year experience. Arthritis Rheum. 2011 Oct;63(10):3163-8. doi: 10.1002/art.30502.

  PMID: 21702011 BACKGROUND

• Shakoor A, Esterberg E, Acharya NR. Recurrence of uveitis after discontinuation of infliximab. Ocul Immunol Inflamm. 2014 Apr;22(2):96-101. doi: 10.3109/09273948.2013.812222. Epub 2013 Jul 22.

  PMID: 23876234 BACKGROUND

• Acharya NR, Ebert CD, Kelly NK, Porco TC, Ramanan AV, Arnold BF; ADJUST Research Group. Discontinuing adalimumab in patients with controlled juvenile idiopathic arthritis-associated uveitis (ADJUST-Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Stopping Trial): study protocol for a randomised controlled trial. Trials. 2020 Oct 27;21(1):887. doi: 10.1186/s13063-020-04796-z.

  PMID: 33109240 BACKGROUND

• Acharya NR, Ramanan AV, Coyne AB, Dudum KL, Rubio EM, Woods SM, Guly CM, Moraitis E, Petrushkin HJD, Armon K, Puvanachandra N, Choi JT, Hawley DP, Arnold BF; ADJUST Study Group. Stopping of adalimumab in juvenile idiopathic arthritis-associated uveitis (ADJUST): a multicentre, double-masked, randomised controlled trial. Lancet. 2025 Jan 25;405(10475):303-313. doi: 10.1016/S0140-6736(24)02468-1.

  PMID: 39863370 RESULT

MeSH Terms

Conditions

Uveitis; Uveitis, Intermediate

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Uveal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Nisha Acharya, MD, MS
• Organization: F.I. Proctor Foundation, University of California, San Francisco

nisha.acharya@ucsf.edu

(415) 476-6687

Study Officials

• Nisha Acharya, MD MS

  Principal Investigator

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Uveitis and Ocular Inflammatory Disease Service

Study Record Dates

• First Submitted: January 22, 2019
• First Posted: January 25, 2019
• Study Start: March 15, 2020
• Primary Completion: January 23, 2025
• Study Completion: April 3, 2025
• Last Updated: May 11, 2025
• Results First Posted: March 26, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (9); AU (1); US (11)