Clinical trial NCT01092533: Myfortic for the Treatment of Non-infectious Intermediate Uveitis
Official title: Myfortic (Enteric-coated Mycophenolate Sodium) for the Treatment of Non-infectious Intermediate Uveitis - a Prospective, Controlled, Randomized Multicenter Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Uveitis, Intermediate
Lead sponsor: STZ eyetrial
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
name: University Hospital Tuebingen
First posted: 2010-03-25
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Time from study entry to first relapse
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin, Augenklinik
city: Freiburg
country: Germany
facility: Universitäts-Augenklinik Freiburg
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg, Interdisziplinäres Uveitiszentrum
city: München
country: Germany
facility: Augenklinik der Ludwig-Maximilians-Universität München
city: Münster
country: Germany
facility: Augenabteilung am St. Franziskus-Hospital Münster
Study officials:
affiliation: Centre for Ophthalmology, University of Tuebingen
name: Christoph Deuter, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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