Clinical Trial Evaluating Rituximab in Ocular Cicatricial Pemphigoid

Study Overview
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Brief Summary
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Cicatricial pemphigoid is an autoimmune blistering disease which affects the skin, mucous membranes, and, in a small subset of patients, the eye. Progressive ocular disease can lead to irreversible damage and blindness. Conventional treatments include systemic steroids, dapsone, and immunosuppressive agents. These treatments, however, are not successful with all patients. Rituximab has been very effective in the treatment of other autoimmune disorders, and has recently been shown to be effective for autoimmune blistering pemphigus. We propose that it will also be effective in the treatment of cicatricial pemphigoid.

Detailed Description
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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.

Official Title
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Phase I/II Clinical Trial Evaluating Rituximab in Ocular Cicatricial Pemphigoid

Conditions
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Ocular Cicatricial Pemphigoid

Intervention / Treatment
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* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 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 Adults age 19 and older Adequate renal function as indicated by serum creatinine levels less than 1.5 Exclusion Criteria: known hypersensitivity to rituximab or its components Age less than 19 years Any other condition deemed by the investigator to be a significant hazard to the subject if the investigational therapy were initiated.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rituximab<br>The Rituximab dose is 1000 mg (1gm) given as an IV infusion every two weeks for 2 doses (Days 1 and 15). | Drug: Rituximab<br>* The Rituximab dose is 1000mg (1gm) given as an IV infusion every two weeks for 2 doses (days 1 and 15).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With no Evidence of Further Scarring (Fosters Staging) at 16 Weeks | Stages Characteristics I Subconjunctival scarring and fibrosis II Fornix foreshortening (a-d describes % loss of inferior fornix depth) 0-25% 25-50% 50-75% 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 | 16 weeks | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pemphigoid, Blistering Diseases, Blindness, Autoimmune, Rituximab