Clinical Trial Evaluating Rituximab in Ocular Cicatricial Pemphigoid

Cicatricial pemphigoid is an autoimmune blistering disease which can affect the skin, mucous membranes, and, in a small subset of patients, the eyes. Progressive ocular disease can lead to irreversible damage and blindness. Conventional treatments have included high dose systemic steroids, dapsone, and immunosuppressive agents such as azathioprine, methotrexate, cyclophosphamide, and mycophenolate mofetil. However, there are a subgroup of patients who fail to respond to these treatments, develop intolerable side effects, or have contraindications to their use. Patients may also develop resistance to these conventional treatment modalities. For these reasons, alternative treatment modalities are needed. Rituximab has been very effective in the treatment of other autoimmune disorders. It has recently been shown to be effective in the treatment of another autoimmune blistering disorder known as pemphigus. We thus propose that Rituximab will be effective in the treatment of cicatricial pemphigoid.

• Rituximab (Drug): The Rituximab dose is 1000mg (1gm) given as an IV infusion every two weeks for 2 doses (days 1 and 15).

Primary outcomes

• Number of Participants With no Evidence of Further Scarring (Fosters Staging) at 16 Weeks [16 weeks]: Stages Characteristics I Subconjunctival scarring and fibrosis II Fornix foreshortening (a-d describes % loss of inferior fornix depth) 1. 0-25% 2. 25-50% 3. 50-75% 4. 75-100% III Presence of symblepharon and number (n) (a-d describes % of horizontal involvement by symblepharons and n is the number of symblepharons countable) a. 0-25% b. 25-50% c. 50-75% d. 75-100% IV Ankyloblepharon, frozen globe
• 2. The Proportion of Patients That Experience a Grade 3, Grade 4, or Grade 5 Toxicity Based Reaction on the NCI-CTC System at the Time of Their Infusions and During Follow-up Visits. [16 weeks]

Secondary outcomes

• 1. Stability of Visual Acuity (Snellen's Test) at 16 Weeks [16 weeks]
• 2. Stability of Visual Acuity (Snellen's Test) at 24 Weeks [24 weeks]

Sex: All, ages: 19 Years to any

Inclusion Criteria:

1. Clinical diagnosis of ocular cicatricial pemphigoid (symptoms of conjunctivitis, irritation, burning, increased lacrimation, photophobia, dryness of the eyes along with conjunctival inflammation, trichiasis, and scarring
2. One of the following:

   * Failed response to the use of one or more conventional treatments for a minimum of 10 weeks; or
   * Minimal conventional medication doses, with a significant adverse effects, contradiction to use, or progressive disease despite treatment
3. Adults age 19 and older
4. Adequate renal function as indicated by serum creatinine levels less than 1.5

Exclusion Criteria:

1. known hypersensitivity to rituximab or its components
2. Age less than 19 years
3. Any other condition deemed by the investigator to be a significant hazard to the subject if the investigational therapy were initiated.

Participant flow

Outcome results

• Number of Participants With no Evidence of Further Scarring (Fosters Staging) at 16 Weeks (Primary), Number, participants: Rituximab 0
• 2. The Proportion of Patients That Experience a Grade 3, Grade 4, or Grade 5 Toxicity Based Reaction on the NCI-CTC System at the Time of Their Infusions and During Follow-up Visits. (Primary)
• 1. Stability of Visual Acuity (Snellen's Test) at 16 Weeks (Secondary)
• 2. Stability of Visual Acuity (Snellen's Test) at 24 Weeks (Secondary)

Adverse events

Time frame: 1 year

Limitations and caveats: Genentech closed trial before site was able to enroll 5 patients.

• Study Protocol and Statistical Analysis Plan (PDF, 2006-04-26)

• Craig A Elmets, Principal investigator, University of Alabama at Birmingham