Adalimumab in Uveitis Refractory to Conventional Therapy (ADUR Trial) - Full Text View

Sponsors and Collaborators:	University of Heidelberg Abbott
Information provided by:	University of Heidelberg
ClinicalTrials.gov Identifier:	NCT00348153

Purpose

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	Intervention	Phase
Uveitis	Drug: Adalimumab	Phase II Phase III

Drug Information available for: Adalimumab Tumor Necrosis Factors

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Outcomes Assessor), Active Control, Crossover Assignment, Safety/Efficacy Study
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)

Further study details as provided by University of Heidelberg:

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

Estimated Enrollment:	40
Study Start Date:	August 2006
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00348153

Contacts

Contact: Regina Max, MD

+49(0)62215639921

Regina.Max@uveitiszentrum.de

Locations

Germany
Interdisciplinary Uveitis Center, University of Heidelberg	Recruiting
Heidelberg, Germany, 69120
Contact: Regina Max, MD +49(0)62215639 Regina.Max@uveitiszentrum.de
Contact: Friederike Mackensen, MD +49(0)62215638558 Friederike.Mackensen@uveitiszentrum.de
Principal Investigator: Matthias D Becker, MD, PhD
Sub-Investigator: Regina Max, MD
Sub-Investigator: Friederike Mackensen, MD
Principal Investigator: Hanns M Lorenz, MD
Sub-Investigator: Andreas Perniok, MD

Sponsors and Collaborators

University of Heidelberg

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

More Information

Homepage with further information and downloads This link exits the ClinicalTrials.gov site

Publications:

Becker MD, Smith JR, Max R, Fiehn C. Management of sight-threatening uveitis: new therapeutic options. Drugs. 2005;65(4):497-519. Review.

Lim L, Suhler EB, Smith JR. Biologic therapies for inflammatory eye disease. Clin Experiment Ophthalmol. 2006 May;34(4):365-74.

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.

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.

Study ID Numbers:	EudraCT: 2006-001732-53
Study First Received:	July 3, 2006
Last Updated:	August 11, 2008
ClinicalTrials.gov Identifier:	NCT00348153
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Heidelberg:

Uveitis
Adalimumab
TNF alpha

Study placed in the following topic categories:

Uveitis
Eye Diseases
Adalimumab

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Uveal Diseases
Therapeutic Uses
Antirheumatic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009