UveitisPhase 3ADVISENCT03828019
Adalimumab vs. Conventional Immunosuppression for Uveitis Trial
A Phase 3 study testing Adalimumab (ADA) and Conventional immunosuppression (CON) in people with Uveitis, run by JHSPH Center for Clinical Trials at 26 sites in 3 countries.
Trial summary
Non-infectious intermediate, posterior, and panuveitides are chronic, potentially-blinding diseases. Vision-threatening cases require long-term therapy with oral corticosteroids and immunosuppression. Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- Uveitis
- What is being tested?
- Adalimumab (ADA) and Conventional immunosuppression (CON)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 227 participants
- Where
- 26 sitesin 3 countries
- Study dates
- 16 Sep 2019to 9 Sep 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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
Who cannot join
- 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%
Show all 30Show fewer
- 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
- Use of anti-TNF monoclonal antibody therapy within past 60 days
- History of adalimumab intolerance or ineffectiveness
- Hypersensitivity to any of the study treatments or their excipients
- Current treatment with an alkylating agent
- Current treatment with more than one immunosuppressive drug, not including oral corticosteroids
- Shorter-acting regional corticosteroids administered within the past 30 days in any eye(s) with uveitis
- Long-acting ocular corticosteroid implants, i.e., fluocinolone acetonide implant (e.g., Retisert®, Yutiq™, Iluvien®) placed within past 3 years unless uveitis is active in all eye(s) with an implant
- Systemic disease that is sufficiently active such that it dictates therapy with systemic corticosteroids or immunosuppressive agents at the time of enrollment
- Immunodeficiency disease for which immunosuppressive therapy would be contraindicated according to best medical judgment
- Pregnancy or lactation
- For persons of child-bearing potential or impregnating potential, unwillingness to use appropriate birth control (abstinence, combination barrier and spermicide, hormonal, or intrauterine device) for the next 18 months or plans to become a biological parent within the next 18 months.
- In the United Kingdom (UK), use of combination barrier and spermicide alone does not meet birth control requirements.
- † UK female study participants must use highly effective methods of contraception.
- UK male study participants must use condoms for at least 6 months after the end of study treatment and their female partners of child-bearing potential are recommended to use highly effective contraception for the same duration. In addition, male participants should not donate semen during therapy or for 6 months following discontinuation of study treatment.
- Medical problems or drug or alcohol dependence problems sufficient to prevent adherence to treatment and study procedures.
Trial locations and contacts
26 sites in 3 countries.
26 sites in 3 countries
United States19 sites
University of Michigan Health System, Kellogg Eye Center
Ann Arbor, Michigan, 48105
Emory University
Atlanta, Georgia, 30322
Johns Hopkins University
Baltimore, Maryland, 21287
Retinal Consultants of Texas
Bellaire, Texas, 77401
National Eye Institute
Bethesda, Maryland, 20892
Ophthalmic Consultants of Boston
Boston, Massachusetts, 02114
Northwestern University
Chicago, Illinois, 60611
Rush University Medical Center
Chicago, Illinois, 60612
University of Iowa
Iowa City, Iowa, 52242
Jules Stein Eye Institute, UCLA
Los Angeles, California, 90095
Anne Bates Leach Eye Hospital, University of Miami Miller School of Medicine
Miami, Florida, 33136
Tennessee Retina
Nashville, Tennessee, 37203
Vanderbilt University Eye Institute
Nashville, Tennessee, 37232
MidAtlantic Retina, Wills Eye Hospital
Philadelphia, Pennsylvania, 19107
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
University of Utah, Moran Eye Center
Salt Lake City, Utah, 84132
University of California, San Francisco
San Francisco, California, 94143
University of Washington, Medicine Eye Institute
Seattle, Washington, 98104
Washington University
St Louis, Missouri, 63110
United Kingdom5 sites
Bradford Teaching Hospital NHS Foundation Trust
Bradford
Cambridge University NHS Trust
Cambridge, CB2 0QQ
University Hospital Birmingham
Edgbaston, Birmingham, B15 2TH
University Hospitals of Leicester
Leicester, LE1 5WW
Moorfields Eye Hospital NHS Foundation Trust
London, EC1V 9EL
Australia2 sites
Centre for Eye Research Australia
East Melbourne, Victoria
University of Sydney
Sydney
About this study
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.
Read the detailed description
Abstract from protocol: The uveitides are a collection of diseases characterized by intraocular inflammation. Collectively, they are the 5th leading cause of blindness in the US, and the estimated cost of treating them is similar to that of treating diabetic retinopathy. Non-infectious intermediate, posterior, and panuveitides have the highest rates of visual loss and typically are treated with oral corticosteroids and immunosuppression. The Multicenter Uveitis Steroid Treatment (MUST) Trial (a randomized, comparative effectiveness trial, which compared 2 treatment paradigms for these diseases, systemic therapy with corticosteroids and immunosuppression vs. regional therapy [the fluocinolone acetonide implant]), and Follow-up Study demonstrated the superiority of the systemic approach to the regional ocular approach in terms of long-term visual outcomes with essentially no increase in systemic side effects in the systemic group. One key to systemic therapy's success was the use of systemic immunosuppression in 88% of participants, coupled with tapering the prednisone to <7.5 mg/day, a relatively safe dose. Non-alkylating agents are typically the first choice and the most often used are azathioprine, methotrexate, mycophenolate, cyclosporine, and tacrolimus. The alkylating agents, cyclophosphamide and chlorambucil, are used less often because of concerns about potential increased malignancy risk. Data from the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study suggest that each of the conventional, non-alkylating agent immunosuppressive drugs is effective in controlling the inflammation while permitting tapering prednisone in ~40-55% of patients; hence combination therapy often is needed. Furthermore, minimizing the daily dose of prednisone is important, as the risk of cardiovascular disease and mortality increase with the cumulative dose of oral corticosteroids. In June 2016, the fully-human, anti-TNF-α monoclonal antibody, adalimumab, was approved by the US Food and Drug Administration (FDA) for the treatment of uveitis. Anti-TNF-α monoclonal antibody therapy has revolutionized the management of the rheumatic diseases largely due to its superior efficacy compared to conventional Disease Modifying Anti-Rheumatic Drugs. Data from VISUAL III, the extension of the two phase 3 trials that led to the FDA approval of adalimumab for the treatment of uveitis, suggest that adalimumab may be superior to conventional immunosuppression, as ~75% of participants had controlled inflammation with prednisone doses <5 mg/day. The ADalimumab Vs. conventional ImmunoSupprEssion for uveitis (ADVISE) Trial is a randomized, comparative effectiveness trial comparing adalimumab to conventional agent immunosuppression for patients with non-infectious, intermediate, posterior, and panuveitides. The primary outcome is the ability to successfully taper prednisone to <7.5 mg/day by 6 months after randomization while maintaining control of the inflammation. Secondary outcomes include prednisone discontinuation by 1 year, visual acuity, and complications of uveitis and its treatment.
ADVISE is being conducted under investigational new drug (IND) 132532. Adalimumab was FDA approved for the treatment of non-infectious intermediate, posterior, and panuveitides in adult patients in 2016 and in pediatric patients 2 years of age and older in 2018. In 2016, prior to the approval for pediatric patients, the FDA determined that use of adalimumab for the treatment of non-infectious intermediate, posterior, and panuveitides in adolescent patients in the ADVISE Trial does not increase risk for these patients as the drug is approved for treatment of pediatric patients for other indications. Although conventional immunosuppressive drugs are the standard approach and in widespread use, these drugs are not FDA approved for treatment of non-infectious intermediate, posterior, and panuveitides, and therefore an IND has been issued for this trial.
- Conditions
- Uveitis
- Being tested
- Adalimumab (ADA), Conventional immunosuppression (CON)
- Keywords
- Immunosuppression, Adalimumab, Antimetabolites, Calcineurin inhibitors, Corticosteroid sparing
- Medical subject headings
- Uveitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adalimumab (ADA)Biological
Also called Adalimumab, Humira
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.
Conventional immunosuppression (CON)Drug
Also called Azathioprine, Imuran , Cyclosporine, Methotrexate, Rheumatrex, Mycophenolate, CellCept, Cyclosporine, Sandimmune, Neoral
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Conventional immunosuppression (CON) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 6 months
Secondary outcomes (14)
Corticosteroid-sparing Treatment Success Within the First 12 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).
Measured: 12 months
Corticosteroid Discontinuation Success by 6 Months
Corticosteroid discontinuation success is defined as achieving inactive uveitis for two consecutive visits >= 28 days apart after discontinuing 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 discontinuation 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 and 12 months.
Measured: 6 months
Corticosteroid Discontinuation Success by 12 Months
Corticosteroid discontinuation success is defined as achieving inactive uveitis for two consecutive visits >= 28 days apart after discontinuing 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 discontinuation 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 and 12 months.
Measured: 12 months
Corticosteroid Exposure Over 12 Months
Corticosteroid dose was collected at baseline and months 1,2,3,4,5,6,8,10, and 12. Mean corticosteroid dose per day was estimated with a negative binomial model at 12 months.
Measured: 12 months
Best Corrected Visual Acuity Change at 12 Months
Mean change in best-corrected visual acuity from baseline to 12 months. Participants' visual acuity was measured by certified examiners with best refractive correction in place. Participants were challenged with reading letters on lines of the standard ETDRS eye chart (5 letters per line). Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until no more meaningful readings could be made and were scored by how many letters could be correctly identified. More letters read is associated with higher visual acuity (85 letters is 20/20 vision). Visual acuity data was collected at baseline and months 1,2,3,4,5,6,8,10, and 12 and estimated at 12 months with a mixed model.
Measured: 12 months
Macular Edema Over 12 Months of Follow up
Macular edema is defined as central retinal thickness greater than or equal to 300 micrometers as measured by a masked grader's review of OCT images. Greater retinal thickness is associated with poorer vision. Outcome measure is the odds ratio comparing macular edema at 12 months to baseline macular edema. Macular edema was measured at baseline and months 3, 6, and 12. The odds ratio at 12 months was estimated with a mixed model.
Measured: 12 months
Incidence of Infections at 12 Months
Incidence of infections over 12 months of follow-up. Participants were asked about occurrences since the previous visit of infections requiring antibiotic or antiviral treatment. Data was collected at months 1,2,3,4,5,6,8,10, and 12. The rate of infections at 12 months was estimated with a negative binomial model.
Measured: 12 months
Elevated Levels of AST or ALT (Hepatoxicity) by 12 Months.
Cumulative percent of participants having elevated levels of aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than twice the upper level of normal by 12 months. Elevated levels of AST and ALT may indicate decline in liver function. Lab values of AST and ALT were measured at baseline and months 1,2,3,4,5,6,8,10, and 12 and the cumulative percent of participants with elevated lab values by 12 months was estimated by Kaplan Meier methods.
Measured: 12 months
Elevated Creatine (Nephrotoxicity) by 12 Months
Cumulative percent of participants having elevated creatine values (creatine greater than 30% above baseline or creatine > 1.5 mg/dL) by 12 months. Increases in creatine levels may indicate decreased kidney function. Lab values of creatine were measured at baseline and months 1,2,3,4,5,6,8,10, and 12 and the cumulative percent of participants with elevated creatine at 12 months was estimated by Kaplan Meier methods.
Measured: 12 months
EQ-5D (Health Utility)
The EQ-5D (EuroQol Group - 5 Dimension questionnaire) is a participant reported validated questionnaire that measures the patient's health status in five dimensions of health: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. The range of questionnaire index scores is -0.59 to 1 where score of 1 indicates best possible health. The outcome measure is the odds of having EQ-5D score of 1 (perfect health) at 12 months compared to the odds of having EQ-5d score = 1 at the baseline visit. Participants completed the EQ-5D questionnaire at baseline and months 3, 6 and 12. General estimating equations with a log link were used to assess the odds ratio at 12 months.
Measured: 12 months
General Health-related Quality of Life -Physical Component (SF-36)
Standard Form 36 item (SF-36) questionnaire is a validated participant reported measure of health related-quality of life.
The physical component summary (PCS) is a score derived from the SF-36 that reflects a person's physical well-being.
Range of scores is 0 to 100. Higher scores indicated better physical health. The minimally important clinical difference is 3-5 points.
Outcome measure is the change in physical health score from baseline to 12 months. Participants completed the questionnaire at baseline and months 3, 6, and 12. The mean change from baseline at 12 months was estimated with a mixed model.
Measured: 12 months
Quality of Life Mental Health Component Standard Form 36 Item (SF-36)
Standard Form 36 item (SF-36) questionnaire is a validated participant reported measure of health related-quality of life.
The mental health component summary (MCS) is a score derived from the SF-36 that reflects a person's mental health and well-being. Range of scores is 0 to 100. Higher scores indicate better mental health. The minimally important clinical difference is 3-5 points. Outcome measure is the change in mental health score from baseline to 12 months. Participants completed the questionnaire at baseline and months 3, 6, and 12. The change from baseline at 12 months was estimated with a mixed model.
Measured: 12 months
Vision-related Quality of Life
Vision-related quality of life was measured by the vision targeted subscale (excluding general health) from the National Eye Institute Visual Functioning Questionnaire 25 item (VFQ-25). The VFQ-25 is a validated, participant reported measure of the aspects of visual functioning that are most important for persons who have chronic eye diseases. Higher scores indicate better vision. Scores range from 0 to 100. Meaningful difference is 4-6 points. Participants completed the VFQ-25 at baseline and months 3, 6 and 12. The outcome is the change in VFQ-25 from baseline to 12 months estimated with a mixed model.
Measured: 12 months
Cataract Surgery at 12 Months
Cumulative percent of uveitis eyes having cataract surgery by 12 months. Whether the patient had cataract surgery in the prior time period was determined at baseline and months 1,2,3,4,5,6,8,10,12 and the cumulative percent of eyes having cataract surgery by12 months was estimated by Kaplan-Meier methods.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2019
- Study start16 Sep 2019
- Primary completion2 Apr 2024
- Study completion9 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for UveitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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,
- Masking
- None (open label)
- Enrolment
- 227 participants (actual)
Sponsor and investigators
- Lead sponsor
- JHSPH Center for Clinical Trials
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Douglas A Jabs, MD MBA, Study chair, CCTand Evidence Synthesis, JHU, Bloomberg School of Public Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03828019
- Sponsor's protocol ID
- 9196
- Acronym
- ADVISE
- Status last verified
- Apr 2025
- First submitted
- 28 Jan 2019
- Last updated
- 16 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: A public use dataset corresponding to the primary manuscript and compliant with HIPAA regulations will be prepared within 1 year of completion of data collection. 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 (see access criteria below).
Publications
Davis JL. Defining Retinal Vasculitis. Am J Ophthalmol. 2024 Nov;267:84-89. doi: 10.1016/j.ajo.2024.05.030. Epub 2024 Jun 24.
PubMed 38925285Teabagy 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.
PubMed 37172782
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adalimumab vs. Conventional Immunosuppression for Uveitis Trial
- ClinicalTrials.gov ID
- NCT03828019
- Acronym / sponsor ID
- ADVISE / 9196
- Conditions
- Uveitis
- Keywords
- Immunosuppression, Adalimumab, Antimetabolites, Calcineurin inhibitors, Corticosteroid sparing
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 227 participants (actual)
- Lead sponsor
- JHSPH Center for Clinical TrialsUniversity, hospital or other
- Study start
- 16 Sep 2019 (actual)
- Primary completion
- 2 Apr 2024 (actual)
- Study completion
- 9 Sep 2024 (actual)
- First posted
- 4 Feb 2019 (actual)
- Results
- Posted 16 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Abstract from protocol: The uveitides are a collection of diseases characterized by intraocular inflammation. Collectively, they are the 5th leading cause of blindness in the US, and the estimated cost of treating them is similar to that of treating diabetic retinopathy. Non-infectious intermediate, posterior, and panuveitides have the highest rates of visual loss and typically are treated with oral corticosteroids and immunosuppression. The Multicenter Uveitis Steroid Treatment (MUST) Trial (a randomized, comparative effectiveness trial, which compared 2 treatment paradigms for these diseases, systemic therapy with corticosteroids and immunosuppression vs. regional therapy [the fluocinolone acetonide implant]), and Follow-up Study demonstrated the superiority of the systemic approach to the regional ocular approach in terms of long-term visual outcomes with essentially no increase in systemic side effects in the systemic group. One key to systemic therapy's success was the use of systemic immunosuppression in 88% of participants, coupled with tapering the prednisone to <7.5 mg/day, a relatively safe dose. Non-alkylating agents are typically the first choice and the most often used are azathioprine, methotrexate, mycophenolate, cyclosporine, and tacrolimus. The alkylating agents, cyclophosphamide and chlorambucil, are used less often because of concerns about potential increased malignancy risk. Data from the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study suggest that each of the conventional, non-alkylating agent immunosuppressive drugs is effective in controlling the inflammation while permitting tapering prednisone in ~40-55% of patients; hence combination therapy often is needed. Furthermore, minimizing the daily dose of prednisone is important, as the risk of cardiovascular disease and mortality increase with the cumulative dose of oral corticosteroids. In June 2016, the fully-human, anti-TNF-α monoclonal antibody, adalimumab, was approved by the US Food and Drug Administration (FDA) for the treatment of uveitis. Anti-TNF-α monoclonal antibody therapy has revolutionized the management of the rheumatic diseases largely due to its superior efficacy compared to conventional Disease Modifying Anti-Rheumatic Drugs. Data from VISUAL III, the extension of the two phase 3 trials that led to the FDA approval of adalimumab for the treatment of uveitis, suggest that adalimumab may be superior to conventional immunosuppression, as ~75% of participants had controlled inflammation with prednisone doses <5 mg/day. The ADalimumab Vs. conventional ImmunoSupprEssion for uveitis (ADVISE) Trial is a randomized, comparative effectiveness trial comparing adalimumab to conventional agent immunosuppression for patients with non-infectious, intermediate, posterior, and panuveitides. The primary outcome is the ability to successfully taper prednisone to <7.5 mg/day by 6 months after randomization while maintaining control of the inflammation. Secondary outcomes include prednisone discontinuation by 1 year, visual acuity, and complications of uveitis and its treatment.
ADVISE is being conducted under investigational new drug (IND) 132532. Adalimumab was FDA approved for the treatment of non-infectious intermediate, posterior, and panuveitides in adult patients in 2016 and in pediatric patients 2 years of age and older in 2018. In 2016, prior to the approval for pediatric patients, the FDA determined that use of adalimumab for the treatment of non-infectious intermediate, posterior, and panuveitides in adolescent patients in the ADVISE Trial does not increase risk for these patients as the drug is approved for treatment of pediatric patients for other indications. Although conventional immunosuppressive drugs are the standard approach and in widespread use, these drugs are not FDA approved for treatment of non-infectious intermediate, posterior, and panuveitides, and therefore an IND has been issued for this trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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,
| Arm | Type | Receives |
|---|---|---|
| Adalimumab (ADA) | Active comparator | Biological: Adalimumab (ADA)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. |
| Conventional immunosuppression (CON) | Active comparator | Drug: Conventional immunosuppression (CON)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. |
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
- Initiation or addition of an immunosuppressive drug (i.e., a conventional immunosuppressive drug or adalimumab) is indicated
Key exclusion criteria (30 listed)
- 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
- Behçet disease
- Multiple sclerosis or other demyelinating disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Adalimumab (ADA)Also: Adalimumab, HumiraAdalimumab 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. | Biological | Adalimumab (ADA) |
| Conventional immunosuppression (CON)Also: Azathioprine, Imuran , Cyclosporine, Methotrexate, Rheumatrex, Mycophenolate, CellCept, Cyclosporine, Sandimmune, NeoralThe 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. | Drug | Conventional immunosuppression (CON) |
Primary outcome
Corticosteroid-sparing Treatment Success Within the First 6 Months After Randomization
Time frame: 6 months
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).
14 secondary outcomes
Corticosteroid-sparing Treatment Success Within the First 12 Months After Randomization
Time frame: 12 months
Corticosteroid Discontinuation Success by 6 Months
Time frame: 6 months
Corticosteroid Discontinuation Success by 12 Months
Time frame: 12 months
Corticosteroid Exposure Over 12 Months
Time frame: 12 months
Best Corrected Visual Acuity Change at 12 Months
Time frame: 12 months
Macular Edema Over 12 Months of Follow up
Time frame: 12 months
Incidence of Infections at 12 Months
Time frame: 12 months
Elevated Levels of AST or ALT (Hepatoxicity) by 12 Months.
Time frame: 12 months
Elevated Creatine (Nephrotoxicity) by 12 Months
Time frame: 12 months
EQ-5D (Health Utility)
Time frame: 12 months
General Health-related Quality of Life -Physical Component (SF-36)
Time frame: 12 months
Quality of Life Mental Health Component Standard Form 36 Item (SF-36)
Time frame: 12 months
Vision-related Quality of Life
Time frame: 12 months
Cataract Surgery at 12 Months
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38925285Davis JL. Defining Retinal Vasculitis. Am J Ophthalmol. 2024 Nov;267:84-89. doi: 10.1016/j.ajo.2024.05.030. Epub 2024 Jun 24.
- Derived from this study: PubMed 37172782Teabagy 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.
- Individual participant dataSharing planned: Yes. A public use dataset corresponding to the primary manuscript and compliant with HIPAA regulations will be prepared within 1 year of completion of data collection. 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 (see access criteria below).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Douglas A Jabs, MD MBA study chair
CCTand Evidence Synthesis, JHU, Bloomberg School of Public Health
26 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Adalimumab (ADA) and Conventional immunosuppression (CON) in people with Uveitis, run by JHSPH Center for Clinical Trials at 26 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, United Kingdom, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Corticosteroid-sparing Treatment Success Within the First 6 Months After Randomization (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03828019, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2025.