Myfortic for the Treatment of Non-infectious Intermediate Uveitis

NCT ID: NCT01092533

Last Updated: 2017-05-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

44 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-03-31

Study Completion Date

2015-10-31

Brief Summary

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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).

Detailed Description

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Mycophenolate mofetil (MMF), a pro-drug containing mycophenolic acid (MPA) as active agent, is approved for the treatment of acute graft rejection after kidney-, heart- and liver-transplantation, and was shown in 1995 to be effective in inhibiting the development of experimental autoimmune uveoretinitis. Further studies proved it to be a safe and effective steroid-sparing immunomodulatory for reducing the recurrence rate of non-infectious intermediate uveitis in humans. Although the adverse effect profile of MMF is comparatively benign, gastrointestinal adverse effects are a major concern and may limit its clinical benefit, because they may necessitate dose reduction, interruption, or even discontinuation of MMF.

An enteric-coated formulation of mycophenolate sodium (EC-MPS, Myfortic) has been developed especially to reduce MPA-related gastrointestinal adverse events. This clinical trial is a prospective controlled study to evaluate whether a Myfortic based regimen will be able to reduce the probability of a relapse compared to steroid therapy alone and to test whether a Myfortic based therapy provides a superior behaviour compared to a steroid regimen.

Conditions

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Uveitis, Intermediate

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Open Label

Study Groups

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Mycophenolate sodium + Prednisolone

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

Group Type EXPERIMENTAL

Myfortic

Intervention Type DRUG

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

Decortin

Intervention Type DRUG

Maintenance dose 5 mg/d

Prednisolone

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

Group Type ACTIVE_COMPARATOR

Decortin

Intervention Type DRUG

Maintenance dose 5 mg/d

Interventions

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Myfortic

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

Intervention Type DRUG

Decortin

Maintenance dose 5 mg/d

Intervention Type DRUG

Other Intervention Names

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Mycophenolate Sodium Prednisolone

Eligibility Criteria

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Inclusion Criteria

* 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:

1. Postmenopausal females, defined as:

c. Females over the age of 60 years. d. Females who are 45 to 60 years of age must be amenorrheic for at least 2 years.
2. Females who had a hysterectomy and/or bilateral oophorectomy.

Exclusion Criteria

* 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)
* Alanine transaminase (ALT), aspartate transaminase (AST), or gamma-glutamyl transferase (GGT) ≥ 2x upper limit of normal (ULN)
* Severe anemia (hemoglobin \< 8 g/dL), leukopenia (white blood cell count \[WBC\] \< 2500 mm3), thrombocytopenia (platelet count \< 80,000 mm3)
* Current malignancy or a history of malignancy within the previous 5 years
* Pregnant or lactating women
* Known allergy for fluorescein natrium
* Currently participating in another clinical trial with an investigational agent in the 30 days prior to study participation and/or has not recovered from any reversible effects or side effects of prior investigational agent
* Subjects with non-ocular, medically significant co-morbid conditions that impair normal activities, require systemic corticosteroids or immunosuppressives, or any medical condition that would likely have an impact on the participant´s ability to comply with the study visit schedule
* Any current or history of substance abuse, psychiatric disorder or a condition that, in the opinion of the investigator, may invalidate communication
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

University Hospital Tuebingen

OTHER

Sponsor Role collaborator

STZ eyetrial

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christoph Deuter, Dr.

Role: PRINCIPAL_INVESTIGATOR

Centre for Ophthalmology, University of Tuebingen

Locations

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Charité Universitätsmedizin Berlin, Augenklinik

Berlin, , Germany

Site Status

Universitäts-Augenklinik Freiburg

Freiburg im Breisgau, , Germany

Site Status

Universitätsklinikum Heidelberg, Interdisziplinäres Uveitiszentrum

Heidelberg, , Germany

Site Status

Augenklinik der Ludwig-Maximilians-Universität München

München, , Germany

Site Status

Augenabteilung am St. Franziskus-Hospital Münster

Münster, , Germany

Site Status

Countries

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Germany

References

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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.

Reference Type BACKGROUND
PMID: 16196117 (View on PubMed)

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

Reference Type 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.

Reference Type BACKGROUND
PMID: 8549684 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11490743 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12750115 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14641155 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16061096 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16163494 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1857605 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11522119 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14974945 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1497494 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18236373 (View on PubMed)

Other Identifiers

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2009-009998-10

Identifier Type: -

Identifier Source: org_study_id

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