Myfortic for the Treatment of Non-infectious Intermediate Uveitis

Myfortic (Enteric-coated Mycophenolate Sodium) for the Treatment of Non-infectious Intermediate Uveitis - a Prospective, Controlled, Randomized Multicenter Trial

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).

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.

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