Clinical Trial Evaluating Rituximab in Ocular Cicatricial Pemphigoid

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

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.

Study Overview

• Status: Completed
• Conditions: Ocular Cicatricial Pemphigoid
• Intervention / Treatment: Drug: Rituximab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Collaborators: Genentech, Inc.; Biogen
• Investigators: Principal Investigator: Craig A Elmets, University of Alabama at Birmingham

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: December 26, 2007
• First Submitted That Met QC Criteria: December 31, 2007
• First Posted (Estimate): January 2, 2008

Study Record Updates

• Last Update Posted (Actual): February 7, 2018
• Last Update Submitted That Met QC Criteria: January 11, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Rituximab; Blindness; Autoimmune; Pemphigoid; Blistering Diseases
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Autoimmune Diseases; Eye Diseases; Skin Diseases, Vesiculobullous; Conjunctival Diseases; Pemphigoid, Bullous; Pemphigoid, Benign Mucous Membrane; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: F060213003