Adalimumab vs. Conventional Immunosuppression for Uveitis Trial

NCT03828019 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 9196
• Study Type: interventional
• Target: 227
• Locations: 3 countries
• Sites: 26

Brief Summary

Non-infectious intermediate, posterior, and panuveitides are chronic, potentially-blinding diseases. Vision-threatening cases require long-term therapy with oral corticosteroids and immunosuppression. Based upon preliminary data, adalimumab, a fully-human, anti-tumor necrosis(TNF)-α monoclonal antibody, now US FDA-approved for uveitis treatment, may be a superior corticosteroid-sparing agent than conventional immunosuppressive drugs. The ADVISE Trial is multicenter randomized, parallel-treatment, comparative effectiveness trial comparing adalimumab to conventional (small molecule) immunosuppression for corticosteroid spring in the treatment of non-infectious, intermediate, posterior, and panuveitides.

Conditions

Uveitis

Keywords

Immunosuppression; Adalimumab; Antimetabolites; Calcineurin inhibitors; Corticosteroid sparing

Outcome Measures

Primary Outcomes (1)

• Corticosteroid-sparing Treatment Success Within the First 6 Months After Randomization

  Corticosteroid-sparing success is defined as achieving inactive uveitis for two consecutive visits \>= 28 days apart while on \<= 7.5 mg/day of corticosteroids. Uveitis status (active vs inactive) is determined by the study ophthalmologist after reviewing the eye exam and imaging. Steroid dose and uveitis activity from visit months 6,8,10 and 12 were included in the analysis. Generalized estimating equations were used to fit logistic regression models to compare the cumulative proportion of corticosteroid sparing between the two treatment groups over time while accounting for correlation between replicate measurements on the same individual with an unstructured covariance matrix. Results were reported at 6 months (primary outcome) and 12 months (secondary outcome).

  6 months

Secondary Outcomes (14)

• Corticosteroid-sparing Treatment Success Within the First 12 Months After Randomization

  12 months

• Corticosteroid Discontinuation Success by 6 Months

  6 months

• Corticosteroid Discontinuation Success by 12 Months

  12 months

• Corticosteroid Exposure Over 12 Months

  12 months

• Best Corrected Visual Acuity Change at 12 Months

  12 months

Study Arms (2)

Adalimumab (ADA)

ACTIVE COMPARATOR

Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks.

Biological: Adalimumab (ADA)

Conventional immunosuppression (CON)

ACTIVE COMPARATOR

Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm twice daily (BID); max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID.

Drug: Conventional immunosuppression (CON)

Interventions

Adalimumab (ADA) BIOLOGICAL

Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.

Also known as: Adalimumab, Humira

Adalimumab (ADA)

Conventional immunosuppression (CON) DRUG

The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.

Also known as: Azathioprine, Imuran , Cyclosporine, Methotrexate, Rheumatrex, Mycophenolate, CellCept, Cyclosporine, Sandimmune, Neoral, Tacrolimus, Prograf

Conventional immunosuppression (CON)

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 13 years or older
• Weight 30 kg (66 lbs) or greater
• Active or recently active (≤ 60 days) non-infectious intermediate, posterior, or panuveitis
• Prednisone indication meets one of the following:
• Active uveitis requiring one of the following i. Initiation of prednisone at dose greater than 7.5 mg/day ii. Increasing prednisone dose to greater than 7.5 mg/day iii. Currently receiving dose greater than 7.5 mg/day
• Inactive uveitis on current dose greater 7.5 mg/day
• Initiation or addition of an immunosuppressive drug (i.e., a conventional immunosuppressive drug or adalimumab) is indicated
• If currently receiving a conventional immunosuppressive drug, the drug and dose have been stable for at least 30 days
• Patient able and willing to self-administer subcutaneous injections or have a qualified person available to administer subcutaneous injections
• If posterior segment disease is present, ability to assess activity in at least one eye with uveitis
• Visual acuity of light perception or better in at least one eye with uveitis

You may not qualify if:

• Active tuberculosis or untreated latent tuberculosis (e.g., positive interferon-γ release assay \[Interferon-gamma release assay (IGRA) test, such as Quantiferon-gold)
• Untreated active hepatitis B or C infection
• Any of the following baseline lab values
• White blood count \<3500 cells per microliter
• Platelets \<100,000 per microliter
• Hematocrit \<30%
• aspartate aminotransferase (AST) or alanine transaminase (ALT) \>1.5 times (X) upper limit normal value
• Serum creatinine \>1.1 times (X) upper limit normal value
• Behçet disease
• Multiple sclerosis or other demyelinating disease
• For patients with anterior/intermediate or intermediate uveitis without systemic disease, abnormal magnetic resonance imaging (MRI) of the brain consistent with demyelinating disease
• Severe uncontrolled infection
• Receipt of a live vaccine within past 30 days
• Moderate to severe heart failure (NYHA class III/IV)
• Active malignancy

Sponsors & Collaborators

• JHSPH Center for Clinical Trials: lead

Study Sites (26)

Jules Stein Eye Institute, UCLA

Los Angeles, California, 90095, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Anne Bates Leach Eye Hospital, University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

National Eye Institute

Bethesda, Maryland, 20892, United States

Location

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

Location

University of Michigan Health System, Kellogg Eye Center

Ann Arbor, Michigan, 48105, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

MidAtlantic Retina, Wills Eye Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Tennessee Retina

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Eye Institute

Nashville, Tennessee, 37232, United States

Location

Retinal Consultants of Texas

Bellaire, Texas, 77401, United States

Location

University of Utah, Moran Eye Center

Salt Lake City, Utah, 84132, United States

Location

University of Washington, Medicine Eye Institute

Seattle, Washington, 98104, United States

Location

Centre for Eye Research Australia

East Melbourne, Victoria, Australia

Location

University of Sydney

Sydney, Australia

Location

University Hospital Birmingham

Edgbaston, Birmingham, B15 2TH, United Kingdom

Location

Bradford Teaching Hospital NHS Foundation Trust

Bradford, United Kingdom

Location

Cambridge University NHS Trust

Cambridge, CB2 0QQ, United Kingdom

Location

University Hospitals of Leicester

Leicester, LE1 5WW, United Kingdom

Location

Moorfields Eye Hospital NHS Foundation Trust

London, EC1V 9EL, United Kingdom

Location

Related Publications (1)

• Teabagy S, Wood E, Bilsbury E, Doherty S, Janardhana P, Lee DJ. Ocular immunosuppressive microenvironment and novel drug delivery for control of uveitis. Adv Drug Deliv Rev. 2023 Jul;198:114869. doi: 10.1016/j.addr.2023.114869. Epub 2023 May 10.

  PMID: 37172782 DERIVED

MeSH Terms

Conditions

Uveitis

Interventions

Adalimumab; Azathioprine; Cyclosporine; Methotrexate; Mycophenolic Acid; Tacrolimus

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; Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Aminopterin; Pterins; Pteridines; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones

Results Point of Contact

• Title: Elizabeth E. Sugar
• Organization: JHSPH Center for Clinical Trials

esugar2@jhu.edu

410-614-7837

Study Officials

• Douglas A Jabs, MD MBA

  CCTand Evidence Synthesis, JHU, Bloomberg School of Public Health

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Unmasked treatment administration and outcome assessments (participants, study ophthalmologists, visual function examiners, and study coordinators are all unmasked). Masked assessment of baseline, 1-month, 3-month, and 6-month photographic images and optical coherence tomography (OCT) by the Reading Center (graders masked).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized treatment assignment with allocation ratio: 1:1 and two stratification variables: (1) number of immunosuppressive drug patient is on at time of enrollment (zero vs. one); (2) Initial dose of prednisone patient will be on in trial (\<30 mg/day vs. ≥30 mg/day). The unit of randomization is the patient,

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: February 4, 2019
• Study Start: September 16, 2019
• Primary Completion: April 2, 2024
• Study Completion: September 9, 2024
• Last Updated: May 16, 2025
• Results First Posted: May 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: One year after completion of data collection, the data set will be available upon request .
• Access Criteria: Requests for access to data will be reviewed by the Executive Committee to confirm oversight authority approval (e.g. institutional review board (IRB) approval) and a minimum standard of scientific merit. Once a request is approved, the investigator will be required to sign a data use agreement approved by the Johns Hopkins Bloomberg School of Public Health Office of Research Administration. An encrypted data set containing de-identified data, a data dictionary and other study documentation (e.g. protocol and study manuals) will be provide after the data use agreement has been executed.

Locations

AU (2); US (19); GB (5)