Use of Infliximab for the Treatment of Pemphigus Vulgaris
Condition: Pemphigus
MeSH terms: Pemphigus
Intervention: Infliximab; Placebo Comparator
Intervention description: Chimeric IgG monoclonal antibody that binds to TNF-alpha, generally used to treat Crohn's disease, given in a dosage of 5 mg/kg; Placebo administered in place of infliximab for control group
Intervention MeSH terms: Infliximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Skin Diseases; Autoimmune Diseases

Summary:

      Pemphigus vulgaris (PV) is a rare skin disorder that causes blistering of the skin and mucous
      membranes. Infliximab is a man-made antibody used to treat certain types of immune system
      disorders, including rheumatoid arthritis and Crohn's disease. This study will determine if
      infliximab given in combination with prednisone is a safe and effective treatment for adults
      with PV.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Positive direct immunofluorescence of patient's skin showing IgG or complement C3
             protein on cell surface with histopathology of lesional skin biopsies consistent with
             diagnosis of pemphigus vulgaris

          -  Failure to completely respond to standard steroid therapy (equivalent to prednisone 1
             to 2 mg/kg/day followed by tapering)

          -  Systemic corticosteroid therapy of at least 20 mg prednisone daily and no more than
             120 mg/day

          -  Inability to reduce systemic corticosteroid dosage below 20 mg/day for at least 8
             weeks

          -  Stable dosage of prednisone for at least 2 weeks prior to study entry

          -  Oral/mucosal disease or skin disease. Detailed information about this criterion can be
             found in the protocol

          -  Willing to comply with the study protocol

          -  Willing to use acceptable means of contraception for the duration of the study and for
             6 months after the end of the study

        Exclusion Criteria:

          -  Positive tuberculosis (TB) test within 1 month prior to first administration of study
             drug

          -  History of latent or active TB prior to screening

          -  Signs or symptoms suggestive of TB disease by medical history or physical examination
             within 3 months prior to first administration of study drug

          -  Posterior/anterior/lateral chest radiograph within 3 months prior to screening showing
             evidence of cancer, infection, or abnormalities (apical scarring) suggestive of
             previous TB

          -  Serious infection, hospitalization for an infection, or treatment with intravenous
             (IV) antibiotics for an infection within 2 months prior to screening. Patients who
             have had less serious infections are eligible for this study at the discretion of the
             investigator.

          -  History or presence of opportunistic infections within 6 months prior to screening

          -  History of receiving human/murine recombinant products

          -  Known allergy to murine products or other chimeric proteins

          -  Human immunodeficiency virus (HIV) infected

          -  Chronic hepatitis B or hepatitis C virus infection

          -  History of hepatitis C virus infection

          -  Cancer within the 5 years prior to study entry. Patients with completely resected
             non-melanoma skin cancers are not excluded.

          -  History or presence of congestive heart failure

          -  History or presence of seizure or demyelinating disorder

          -  History of latent or active granulomatous infection, including TB, histoplasmosis, or
             coccidioidomycosis

          -  Received a Bacillus Calmette-Guerin (BCG) vaccine within 12 months of screening

          -  History of lymphoproliferative disease, including lymphoma or signs and symptoms of
             possible lymphoproliferative disease, such as lymphadenopathy of unusual size or
             location or enlarged spleen

          -  Current signs or symptoms of severe progressive or uncontrolled kidney, liver, blood,
             gastrointestinal, endocrine, lung, heart, neurologic, or cerebral disease

          -  Have had chronic or recurrent infectious disease including, but not limited to,
             chronic kidney infection, chronic chest infection, sinusitis, recurrent urinary tract
             infection, infected skin wound, or ulcer

          -  Previous treatment with infliximab, other monoclonal antibodies, or antibody fragments

          -  Previous treatment with etanercept or other anti-tumor necrosis factor (TNF) agents in
             the 3 months prior to screening

          -  Treatment with methotrexate, azathioprine, mycophenolate mofetil, plasmapheresis, IV
             immunoglobulin, pulse systemic corticosteroids, or other systemic immunosuppressive
             agents within the 4 weeks prior to study entry

          -  History of alcohol or drug abuse within the 3 years prior to study entry

          -  History of noncompliance to medical regimens

          -  History of a systemic inflammatory disease other than pemphigus vulgaris

          -  History of a medical condition that would interfere with participation or increase the
             risk to the participant

          -  Unable or unwilling to undergo blood draws because of poor tolerability or lack of
             easy access

          -  Use of any investigational drug within 30 days prior to screening OR within 5
             half-lives of the investigational agent, whichever is longer

          -  Participation in another investigative clinical trial

          -  Presence of transplanted solid organ. Participants who have received a corneal
             transplant more than 3 months prior to screening are not excluded.

          -  Require certain medications

          -  Other conditions or circumstances that could interfere with participant's adherence to
             the study requirements

          -  Pregnancy, breastfeeding, or plans to become pregnant