Adalimumab in Uveitis Refractory to Conventional Therapy (ADUR Trial)

Sponsor

Heidelberg University (Other)

Overall Status

Unknown status

CT.gov ID

NCT00348153

Collaborator

Abbott (Industry)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Uveitis	Drug: Adalimumab	Phase 2/Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Aug 1, 2006

Actual Primary Completion Date :

Sep 1, 2012

Anticipated Study Completion Date :

Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Adalimumab + corticosteroids + immunosuppressive treatments Adalimumab 40 mg eow, stable immunosuppression, corticosteroids in 1 mg/kg/Bodyweight (max. 80 mg) and taper	Drug: Adalimumab
Active Comparator: immunosuppressive treatment + corticosteroids corticosteroids upped to 1mg/kg/Bodyweight and taper, stable immunosuppressive treatment	Drug: Adalimumab

Arm

Intervention/Treatment

Experimental: Adalimumab + corticosteroids + immunosuppressive treatments

Adalimumab 40 mg eow, stable immunosuppression, corticosteroids in 1 mg/kg/Bodyweight (max. 80 mg) and taper

Drug: Adalimumab

Active Comparator: immunosuppressive treatment + corticosteroids

corticosteroids upped to 1mg/kg/Bodyweight and taper, stable immunosuppressive treatment

Drug: Adalimumab

Outcome Measures

Primary Outcome Measures

Improvement of visual acuity (3 lines EDTRS) [at week 0, 2, 6, 12 and 24]

Secondary Outcome Measures

Improvement of intraocular inflammatory activity [at week 0, 2, 6, 12 and 24]
Evolution of cystoid macula edema(FLA, OCT) [at week 0, 6, 12 and 24]
Number of switchers from Arm A to Arm B [after six months]
Cumulative steroid dosage [after six months]
Frequency of adverse events [whole study period]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Interdisciplinary Uveitis Center, University of Heidelberg	Heidelberg		Germany	69120

Sponsors and Collaborators

Heidelberg University
Abbott

Investigators

Principal Investigator: Hannes M Lorenz, MD, Department of Rheumatology, University of Heidelberg
Principal Investigator: Matthias D Becker, MD, Interdisziplinary Uveitis Center, University of Heidelberg
Study Director: Regina Max, MD, Interdisziplinary Uveitis Center, University of Heidelberg