Adalimumab vs. Conventional Immunosuppression for Uveitis Trial



Status:Not yet recruiting
Conditions:Cervical Cancer, Ocular
Therapuetic Areas:Oncology, Ophthalmology
Healthy:No
Age Range:13 - Any
Updated:3/14/2019
Start Date:May 2019
End Date:February 28, 2023
Contact:Janet T Holbrook, PhD MPH
Email:jholbro1@jhu.edu
Phone:443-287-5791

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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-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.

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-alklyating 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 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.

Inclusion Criteria:

1. Age 13 years or older

2. Active or recently active (≤ 60 days) non-infectious, intermediate, posterior, or
panuveitis

3. Prednisone indication meets one of the following:

a. 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

b. Inactive uveitis on current dose greater 7.5 mg/day

4. Initiation or addition of an immunosuppressive drug (i.e., a conventional
immunosuppressive drug or adalimumab) is indicated

5. If currently receiving a conventional immunosuppressive drug, the drug and dose have
been stable for at least 30 days

6. Patient able and willing to self-administer subcutaneous injections or have a
qualified person available to administer subcutaneous injections

7. If posterior segment disease is present, ability to assess activity in at least one
eye with uveitis

8. Visual acuity of light perception or better in at least one eye with uveitis

Exclusion Criteria:

1. Active tuberculosis or untreated latent tuberculosis (e.g., positive interferon-γ
release assay [IGRA] test, such as Quantiferon-gold)

2. Untreated active hepatitis B or C infection

3. Behçet disease

4. Multiple sclerosis

5. For patients with intermediate uveitis, abnormal magnetic resonance imaging (MRI) of
the brain consistent with demyelinating disease

6. Use of anti-TNF monoclonal antibody therapy within past 60 days

7. History of adalimumab intolerance or ineffectiveness

8. Current treatment with an alkylating agent

9. Current treatment with more than one immunosuppressive drug, not including oral
corticosteroids

10. Shorter-acting regional corticosteroids administered within the past 30 days in any
eye(s) with uveitis

11. Long-acting ocular corticosteroid implants, i.e., fluocinolone acetonide implant
(e.g., Retisert®, YutiqTM, Iluvien®) placed within past 3 years unless uveitis is
active in all eye(s) with an implant

12. Systemic disease that is sufficiently active such that it dictates therapy with
systemic corticosteroids or immunosuppressive agents at the time of enrollment

13. Immunodeficiency disease for which immunosuppressive therapy would be contraindicated
according to best medical judgment

14. Pregnancy, lactation, or for women of child-bearing potential unwillingness to use
appropriate birth control for the duration of the trial

15. Medical problems or drug or alcohol dependence problems sufficient to prevent
adherence to treatment and study procedures.
We found this trial at
22
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Houston, Texas 77030
Principal Investigator: Rosa Y Kim, MD
Phone: 713-524-3434
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201 Dowman Dr
Atlanta, Georgia 30303
(404) 727-6123
Principal Investigator: Steven Yeh, MD
Phone: 404-778-2421
Emory University Emory University, recognized internationally for its outstanding liberal artscolleges, graduate and professional schools,...
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3400 N Charles St
Baltimore, Maryland 21205
410-516-8000
Johns Hopkins University The Johns Hopkins University opened in 1876, with the inauguration of its...
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101 Jessup Hall
Iowa City, Iowa 52242
(319) 335-3500
Principal Investigator: James Folk, MD
Phone: 319-467-5184
University of Iowa With just over 30,000 students, the University of Iowa is one of...
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Ann Arbor, Michigan 48105
Principal Investigator: Susan G Elner, MD
Phone: 734-936-0138
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Bethesda, Maryland 20892
Principal Investigator: H. Nida Sen, MD
Phone: 301-435-4529
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Boston, Massachusetts 02114
Principal Investigator: Lana M Rifkin, MD
Phone: 617-314-2703
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243 Charles St
Boston, Massachusetts 02114
(617) 523-7900
Principal Investigator: George Papaliodis, MD
Phone: 617-573-5558
Massachusetts Eye & Ear Infirmary Whether you see our physicians at Mass. Eye and Ear's...
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303 East Superior Street
Chicago, Illinois 60611
Principal Investigator: Anjum Koreishi, MD
Phone: 312-695-0252
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1653 W. Congress Parkway
Chicago, Illinois 60612
(312) 942-5000
Principal Investigator: Pauline T Merrill, MD
Phone: 312-563-4031
Rush University Medical Center Rush University Medical Center encompasses a 664-bed hospital serving adults and...
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Durham, North Carolina 27710
Principal Investigator: Glenn J Jaffe, MD
Phone: 919-684-9072
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East Melbourne, Victoria
Principal Investigator: Lyndell Lim, MD
Phone: +61 3 9929 8087
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Los Angeles, California
Principal Investigator: Gary Holland, MD
Phone: 310-794-5604
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500 S Preston St
Louisville, Kentucky
(502) 852-5555
Principal Investigator: Harpal S Sandhu, MD FRCSC
Phone: 502-852-5251
University of Louisville The University of Louisville is a state supported research university located in...
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Miami, Florida 33136
Principal Investigator: Janet Davis, MD
Phone: 305-326-6348
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Nashville, Tennessee 37232
Principal Investigator: Sapna Gangaputra, MD
Phone: 615-936-1639
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840 Walnut Street
Philadelphia, Pennsylvania 19107
Principal Investigator: James P Dunn, MD
Phone: 215-928-3092
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3451 Walnut St
Philadelphia, Pennsylvania 19104
1 (215) 898-5000
Principal Investigator: Nirali Bhatt, MD
Phone: 215-662-8094
Univ of Pennsylvania Penn has a long and proud tradition of intellectual rigor and pursuit...
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Rochester, Minnesota 55905
Principal Investigator: Wendy Smith, MD
Phone: 507-284-5833
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Salt Lake City, Utah 84132
Principal Investigator: Albert Vitale, MD
Phone: 801-581-6265
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San Francisco, California 94143
Principal Investigator: Nisha Acharya, MD
Phone: 415-476-6687
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Seattle, Washington 98014
Principal Investigator: Kathryn Pepple, MD
Phone: 206-520-9728
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