Clinical trial NCT00348153: Adalimumab in Uveitis Refractory to Conventional Therapy (ADUR Trial)
Official title: Randomized Controlled Study to Evaluate the Efficacy of Adalimumab in Patients With Different Forms of Refractory Uveitis Acronym: Adalimumab in Uveitis Refractory to Conventional Therapy (ADUR Trial)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Uveitis
Keywords: Uveitis
Adalimumab
TNF alpha
Lead sponsor: Heidelberg University
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2006-07-04
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: TNF alpha Inhibitors have been very effective in treating rheumatologic diseases as well as uveitis. Adalimumab is the first member of a new class of TNF antibody compounds developed to contain exclusively human sequences. We want to test the efficacy and safety of the TNF alpha Inhibitor Adalimumab in patients with active uveitis despite standard immunosuppressive therapy.

Detailed description: TNF alpha Inhibitors like Infliximab and Etanercept have been very effective in treating rheumatologic diseases. They have been used to treat severe uveitis by several groups, Suhler and coworkers have published the largest series in 2005. Adalimumab, a recombinant, full-length immunoglobulin, is the first member of a new class of TNF antibody compounds developed to contain exclusively human sequences. The duration of therapeutic efficacy of other TNF antibodies, which contain non-human sequences, may be limited to a greater extent by antibody responses raised in subjects over time. We want to test the efficacy and safety of the TNF alpha Inhibitor Adalimumab in patients with active uveitis despite standard immunosuppressive therapy requiring systemic corticosteroids \> 7,5mg prednisolone.

Eligibility criteria: Inclusion Criteria:

* Male and female patients age 18 and older
* Subjects must meet the criteria for non-infectious uveitis according to the definition of the SUN working group
* Uveitis must have first been diagnosed at least 6 months ago
* Persistence of active disease ( \> 2 flares within 6 months) or progressive deterioration of vision (\< 0,6) within the last 3 months despite immunosuppressive therapy requiring corticosteroids ≥ 7,5 mg prednisone
* Women of childbearing potential have to practice a reliable birth control method throughout the study and until five months after the last administration of Adalimumab
* Ability to comprehend and willing to give informed consent for participation in the study
* Able and willing to self-administer sc injections or assistance of a suitable person to administer sc injections
* Negative PPD skin test or serological testing according to official German recommendations for tuberculosis testing AND chest X-ray within the last three month. Treatment of latent TB with INH must be started 4 weeks prior to administration of first dose of study drug.

Exclusion Criteria:

* Participation in another clinical trial and/or observation period of competing trials
* Treatment with infliximab within the last 2 months or with etanercept within the last 3 weeks
* Patients with only intermediary uveitis or optic neuritis multiple sclerosis
* Patients with uveitis caused by infection
* Patients with optic atrophy, macular scar, cataract, amblyopia or corneal scars
* Patients with recurrent episodes of uveitis, but long intermittent phases of complete remissions without therapy
* Patients possibly demanding vitrectomy or cataract surgery within the time of clinical trial
* Pregnant and nursing women or women planning a pregnancy within 5 months
* Persistent or recurrent infections or severe infections requiring hospitalization with iv antibiotics within 30 days, or oral antibiotics within 14 days prior to enrollment
* Known opportunistic infection (such as herpes zoster) during the last 2 months
* Live vaccination during the last 30 days
* History of tuberculosis; histoplasmosis or listeriosis
* Known HIV infection, active hepatitis B or C
* Comorbidities: uncontrolled diabetes, unstable ischemic heart disease, congestive heart failure (NYHA III, IV), active inflammatory bowl disease, recent stroke (within three months), chronic leg ulcer and similar conditions which would put the subject at risk by participation in the trial
* Previous diagnosis of signs of central nervous system demyelinating diseases
* History of cancer or lymphoproliferative disease other than a successfully and completely treated squamous cell or basal cell carcinoma of the skin or cervical dysplasia, with no recurrence within the last two years
* Hemoglobin \< 10 g/dl, white blood cell count \< 3.0x109/l, platelet count \< 100x109/l, creatinine level \>1.5 mg/dl, liver enzymes \> 1.5 times above normal or alkaline phosphatase \>3 times above normal
* Clinical examination showing significant abnormalities of clinical relevance
* Current evidence of significant abuse of drugs
* Psychiatric disease/social situations that would limit compliance with study requirements

Primary outcomes:
measure: Improvement of visual acuity (3 lines EDTRS)
timeFrame: at week 0, 2, 6, 12 and 24
Secondary outcomes:
measure: Improvement of intraocular inflammatory activity
timeFrame: at week 0, 2, 6, 12 and 24
measure: Evolution of cystoid macula edema(FLA, OCT)
timeFrame: at week 0, 6, 12 and 24
measure: Number of switchers from Arm A to Arm B
timeFrame: after six months
measure: Cumulative steroid dosage
timeFrame: after six months
measure: Frequency of adverse events
timeFrame: whole study period
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: Interdisciplinary Uveitis Center, University of Heidelberg
Study officials:
affiliation: Department of Rheumatology, University of Heidelberg
name: Hannes M Lorenz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Interdisziplinary Uveitis Center, University of Heidelberg
name: Matthias D Becker, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Interdisziplinary Uveitis Center, University of Heidelberg
name: Regina Max, MD
role: STUDY_DIRECTOR
References:
citation: Becker MD, Smith JR, Max R, Fiehn C. Management of sight-threatening uveitis: new therapeutic options. Drugs. 2005;65(4):497-519. doi: 10.2165/00003495-200565040-00005.
citation: Lim L, Suhler EB, Smith JR. Biologic therapies for inflammatory eye disease. Clin Exp Ophthalmol. 2006 May-Jun;34(4):365-74. doi: 10.1111/j.1442-9071.2006.01225.x.
citation: Suhler EB, Smith JR, Wertheim MS, Lauer AK, Kurz DE, Pickard TD, Rosenbaum JT. A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes. Arch Ophthalmol. 2005 Jul;123(7):903-12. doi: 10.1001/archopht.123.7.903.
citation: Smith JR, Levinson RD, Holland GN, Jabs DA, Robinson MR, Whitcup SM, Rosenbaum JT. Differential efficacy of tumor necrosis factor inhibition in the management of inflammatory eye disease and associated rheumatic disease. Arthritis Rheum. 2001 Jun;45(3):252-7. doi: 10.1002/1529-0131(200106)45:33.0.CO;2-5.