Myfortic for the Treatment of Non-infectious Intermediate Uveitis

NCT01092533 | Completed Phase 3 DMC

• 1 other identifier: 2009-009998-10
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 5

Brief Summary

The objective of this clinical trial is to evaluate the efficacy, safety and tolerability of enteric-coated mycophenolate sodium (Myfortic®) in combination with low-dose corticosteroids (Decortin H®) compared to a monotherapy with low-dose corticosteroids (Decortin H®) in subjects with chronic intraocular inflammation (non-infectious intermediate uveitis).

Conditions

Uveitis, Intermediate

Outcome Measures

Primary Outcomes (1)

• Time from study entry to first relapse

  A log-rank test will be used to evaluate differences between the treatment and control group with the null hypothesis of no differences in the survival distributions between the two groups and the alternative hypothesis of different survival distributions. A two-sided log-rank test will be used at a significance level of 0.05.

  6 months

Study Arms (2)

Mycophenolate sodium + Prednisolone

EXPERIMENTAL

Mycophenolate sodium 1440 mg/day Prednisolone: initial dose 1 mg/kg/day, maintenance dose 5 mg/day

Drug: Myfortic; Drug: Decortin

Prednisolone

ACTIVE COMPARATOR

Prednisolone: initial dose 1 mg/kg/day, maintenance dose 5 mg/day

Drug: Decortin

Interventions

Myfortic DRUG

Myfortic 360 mg BID (during week 1) Myfortic 720 mg BID (from week 2 on) Maintenance dose Decortin 5mg/d

Also known as: Mycophenolate Sodium

Mycophenolate sodium + Prednisolone

Decortin DRUG

Maintenance dose 5 mg/d

Also known as: Prednisolone

Mycophenolate sodium + Prednisolone; Prednisolone

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with a documented at least 6 months history of unilateral or bilateral intermediate uveitis either idiopathic or due to non-infectious systemic disease (e.g. sarcoidosis, multiple sclerosis)
• Uveitis has to be considered to be active at the timepoint of enrolment according to at least one of the following criteria:
• Grade 2+ or higher for vitreous haze
• Grade 2+ or higher for anterior chamber cells
• Presence of cystoid macular edema in OCT
• Presence of retinal vessel leakage in FA
• Considered by the investigator to require systemic treatment.
• At least 18 years of age
• Not planning to undergo elective ocular surgery during the study
• Capable of understanding the purposes and risks of the study, able to give informed consent and to comply with the study requirements
• Subjects of both gender with reproductive potential who are sexually active agree to use contraception throughout the course of the study and for at least 3 months after completion of their study participation.
• Women of childbearing potential have to use a highly effective method of birth control defined as one which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, hormonal IUDs combined with barrier methods (e.g. condom, diaphragm or spermicide), sexual abstinence or vasectomised partner.
• Women of childbearing age must have a negative urine pregnancy test (UPT) within 48 hours prior to starting study drug and must not be lactating.
• Female subjects of non-childbearing potential must meet at least one of the following criteria:
• Postmenopausal females, defined as:

You may not qualify if:

• Uveitis of infectious etiology
• Signs of tuberculosis in chest x-ray during the past 12 months before study entry
• Clinically suspected or confirmed central nervous system or ocular lymphoma
• Primary diagnosis of anterior or posterior uveitis
• Uncontrolled glaucoma or known steroid response
• Subjects who received treatment with a systemic immunosuppressive drug, a monoclonal antibody or any other biologic therapy within 90 days prior study entry
• Treatment with mycophenolate mofetil or mycophenolate sodium in the past
• Treatment with a periocular steroid injection within 6 weeks prior to study entry
• Presence of absolute contraindications for Decortin H and/or Myfortic as mentioned in the product informations (Appendix 1 and 2)
• Presence of relative contraindications for Decortin H and/or Myfortic as mentioned in the product information (Appendix 1 and 2) if the disorder leading to the relative contraindication can not sufficiently managed by concomitant medication.
• Recipients of a solid organ transplant
• Subjects with lens opacities or obscured ocular media upon enrolment making unable evaluation of the posterior eye segment
• Subjects with a history of herpes zoster or varicella infection within 3 months before enrollment
• Active, extraocular infection requiring the prolonged or chronic use of antimicrobial agents or the history/presence of active hepatitis A, B or C
• Seropositivity for human immunodeficiency virus (HIV)

Sponsors & Collaborators

• STZ eyetrial: lead
• Novartis Pharmaceuticals: collaborator
• University Hospital Tuebingen: collaborator

Study Sites (5)

Charité Universitätsmedizin Berlin, Augenklinik

Berlin, 13353, Germany

Location

Universitäts-Augenklinik Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Heidelberg, Interdisziplinäres Uveitiszentrum

Heidelberg, 69120, Germany

Location

Augenklinik der Ludwig-Maximilians-Universität München

München, 80336, Germany

Location

Augenabteilung am St. Franziskus-Hospital Münster

Münster, 48145, Germany

Location

Related Publications (13)

• Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005 Sep;140(3):509-16. doi: 10.1016/j.ajo.2005.03.057.

  PMID: 16196117 BACKGROUND

• Whitcup SM. Intermediate uveitis. In: Nussenblatt RB, Whitcup SM (eds.). Uveitis. Fundamentals and clinical practice. Elsevier publishers 2004: 291-300

  BACKGROUND

• Chanaud NP 3rd, Vistica BP, Eugui E, Nussenblatt RB, Allison AC, Gery I. Inhibition of experimental autoimmune uveoretinitis by mycophenolate mofetil, an inhibitor of purine metabolism. Exp Eye Res. 1995 Oct;61(4):429-34. doi: 10.1016/s0014-4835(05)80138-1.

  PMID: 8549684 BACKGROUND

• Zierhut M, Stubiger N, Aboalchamat W, Landenberger H, Bialasiewicz AA, Engelmann K. [Immunosuppressive therapy with mycophenolate mofetil (CellCept) in treatment of uveitis]. Ophthalmologe. 2001 Jul;98(7):647-51. doi: 10.1007/s003470170101. German.

  PMID: 11490743 BACKGROUND

• Baltatzis S, Tufail F, Yu EN, Vredeveld CM, Foster CS. Mycophenolate mofetil as an immunomodulatory agent in the treatment of chronic ocular inflammatory disorders. Ophthalmology. 2003 May;110(5):1061-5. doi: 10.1016/S0161-6420(03)00092-7.

  PMID: 12750115 BACKGROUND

• Lau CH, Comer M, Lightman S. Long-term efficacy of mycophenolate mofetil in the control of severe intraocular inflammation. Clin Exp Ophthalmol. 2003 Dec;31(6):487-91. doi: 10.1046/j.1442-9071.2003.00704.x.

  PMID: 14641155 BACKGROUND

• Thorne JE, Jabs DA, Qazi FA, Nguyen QD, Kempen JH, Dunn JP. Mycophenolate mofetil therapy for inflammatory eye disease. Ophthalmology. 2005 Aug;112(8):1472-7. doi: 10.1016/j.ophtha.2005.02.020.

  PMID: 16061096 BACKGROUND

• Siepmann K, Huber M, Stubiger N, Deuter C, Zierhut M. Mycophenolate mofetil is a highly effective and safe immunosuppressive agent for the treatment of uveitis : a retrospective analysis of 106 patients. Graefes Arch Clin Exp Ophthalmol. 2006 Jul;244(7):788-94. doi: 10.1007/s00417-005-0066-8. Epub 2005 Sep 15.

  PMID: 16163494 BACKGROUND

• Mod A, Tamaska J, Adam E, Gidall J, Poros A, Kiraly A, Natonek K, Paloczi K, Hollan Z. [Importance of the detection of minimal residual disease in the management of acute leukemia]. Orv Hetil. 1991 Jun 16;132(24):1291-6, 1299. Hungarian.

  PMID: 1857605 BACKGROUND

• Behrend M. Adverse gastrointestinal effects of mycophenolate mofetil: aetiology, incidence and management. Drug Saf. 2001;24(9):645-63. doi: 10.2165/00002018-200124090-00002.

  PMID: 11522119 BACKGROUND

• Budde K, Curtis J, Knoll G, Chan L, Neumayer HH, Seifu Y, Hall M; ERL B302 Study Group. Enteric-coated mycophenolate sodium can be safely administered in maintenance renal transplant patients: results of a 1-year study. Am J Transplant. 2004 Feb;4(2):237-43. doi: 10.1046/j.1600-6143.2003.00321.x.

  PMID: 14974945 BACKGROUND

• Hachinski VC, Wilson JX, Smith KE, Cechetto DF. Effect of age on autonomic and cardiac responses in a rat stroke model. Arch Neurol. 1992 Jul;49(7):690-6. doi: 10.1001/archneur.1992.00530310032009.

  PMID: 1497494 BACKGROUND

• Pleyer U, Ruokonen P, Schmidt N, Feist E, Hohne M, Stanojlovic S. [Mycophenol acid in ocular automimmune disorders--can we optimise this therapy?]. Klin Monbl Augenheilkd. 2008 Jan;225(1):66-9. doi: 10.1055/s-2008-1027134. German.

  PMID: 18236373 BACKGROUND

MeSH Terms

Conditions

Uveitis, Intermediate

Interventions

Mycophenolic Acid; Prednisone; Prednisolone

Condition Hierarchy (Ancestors)

Uveitis; Uveal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols

Study Officials

• Christoph Deuter, Dr.

  Centre for Ophthalmology, University of Tuebingen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2010
• First Posted: March 25, 2010
• Study Start: March 1, 2010
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: May 9, 2017

Record last verified: 2017-05

Locations

DE (5)