Adalimumab vs. Conventional Immunosuppression for Uveitis Trial

• Status: Recruiting
• Trial end date: 2024-02-28
• Target enrollment: 0
• Participant gender: All

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-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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: JHSPH Center for Clinical Trials
• Treatments: Adalimumab; Azathioprine; Cyclosporine; Cyclosporins; Methotrexate; Mycophenolic Acid; Tacrolimus

Criteria

Inclusion criteria

1. Age 13 years or older

2. Weight 30 kg (66 lbs) or greater

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

4. Prednisone indication meets one of the following:

1. 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

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

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

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

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

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

9. 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. Any of the following baseline lab values

1. White blood count <3500 cells per microliter

2. Platelets <100,000 per microliter

3. Hematocrit <30%

4. AST or ALT >1.5X upper limit normal value

5. Serum creatinine >1.1X upper limit normal value

4. Behçet disease

5. Multiple sclerosis or other demyelinating disease

6. For patients with anterior/intermediate or intermediate uveitis without systemic disease, abnormal magnetic resonance imaging (MRI) of the brain consistent with demyelinating disease

7. Severe uncontrolled infection

8. Receipt of a live vaccine within past 30 days

9. Moderate to severe heart failure (NYHA class III/IV)

10. Active malignancy

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

12. History of adalimumab intolerance or ineffectiveness

13. Hypersensitivity to any of the study treatments or their excipients

14. Current treatment with an alkylating agent

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

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

17. 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

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

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

20. Pregnancy or lactation

21. 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 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.

22. Medical problems or drug or alcohol dependence problems sufficient to prevent adherence to treatment and study procedures.