Use of Infliximab for the Treatment of Pemphigus Vulgaris

NCT00283712 | Completed Phase 2 Results

• 1 other identifier: DAIT APV01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Pemphigus

Keywords

Skin Diseases; Autoimmune Diseases

Outcome Measures

Primary Outcomes (2)

• Participant Response to Treatment at Week 18

  Participants classified as responders at Week 18 had: 1. Achieved a prednisone dosage \<= 25% of the initial starting dose or \<= 10 mg/day (whichever is greater), and 2. Had no new blisters within the previous 4 weeks.

  Baseline to Week 18

• Treatment-Related Adverse Events >= Grade 3 On or Before Week 18

  Grades were based on the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0. An adverse event (AE) was considered treatment-related if it was classified as unlikely, possibly, probably, or definitely related to study treatment. Participants who experienced at least one treatment-related, grade 3 or higher AE were counted only once. AEs of skin including rash, skin ulceration, and chelitis as defined by the NCI-CTCAE V3.0 System Organ Class of "Skin and Subcutaneous Tissues Disorders" were excluded.

  Baseline to Week 18

Secondary Outcomes (13)

• Participant Response to Treatment at Week 18

  Baseline to Week 18

• Participant Modified Response Status at Week 18

  Baseline to Week 18

• Participant Time to Cessation of New Blisters

  Baseline to Week 26

• Time to 80% Lesion Healing

  Baseline to Week 26

• Total Prednisone Dosage Required for Participants to Achieve Cessation of New Blisters

  Baseline to Week 26

Study Arms (2)

Infliximab

EXPERIMENTAL

Participants are randomized to receive intravenous infusions of infliximab (5mg/kg reconstituted in 10 mL of Sterile Water for Injection, USP ) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a masked (blinded) fashion. Refer to section titled, "Detailed Description" for additional treatment information.

Drug: Infliximab

Placebo Comparator

PLACEBO COMPARATOR

Participants are randomized to receive intravenous infusions of placebo (5 mg/kg comprised of a white lyophilized powder reconstituted in 10 mL of Sterile Water for Injection, USP) at Weeks 0, 2, 6, and 14 over a time period of no less than two hours in a masked (blinded) fashion. Refer to section titled, "Detailed Description" for additional treatment information.

Other: Placebo Comparator

Interventions

Infliximab DRUG

Chimeric IgG monoclonal antibody that binds to TNF-alpha, generally used to treat Crohn's disease, given in a dosage of 5 mg/kg

Also known as: Remicade®

Infliximab

Placebo Comparator OTHER

Placebo administered in place of infliximab for control group

Also known as: Control Arm

Placebo Comparator

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Autoimmunity Centers of Excellence: collaborator

Study Sites (4)

Norris Cancer Center, University of Southern California

Los Angeles, California, 90033, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (5)

• Anhalt GJ, Diaz LA. Pemphigus vulgaris--a model for cutaneous autoimmunity. J Am Acad Dermatol. 2004 Jul;51(1 Suppl):S20-1. doi: 10.1016/j.jaad.2004.01.011. No abstract available.

  PMID: 15243495 BACKGROUND

• Drosou A, Kirsner RS, Welsh E, Sullivan TP, Kerdel FA. Use of infliximab, an anti-tumor necrosis alpha antibody, for inflammatory dermatoses. J Cutan Med Surg. 2003 Sep-Oct;7(5):382-6. doi: 10.1007/s10227-002-0134-1. Epub 2003 Sep 24.

  PMID: 14973643 BACKGROUND

• Jacobi A, Shuler G, Hertl M. Rapid control of therapy-refractory pemphigus vulgaris by treatment with the tumour necrosis factor-alpha inhibitor infliximab. Br J Dermatol. 2005 Aug;153(2):448-9. doi: 10.1111/j.1365-2133.2005.06744.x. No abstract available.

  PMID: 16086769 BACKGROUND

• Pardo J, Mercader P, Mahiques L, Sanchez-Carazo JL, Oliver V, Fortea JM. Infliximab in the management of severe pemphigus vulgaris. Br J Dermatol. 2005 Jul;153(1):222-3. doi: 10.1111/j.1365-2133.2005.06672.x. No abstract available.

  PMID: 16029365 BACKGROUND

• Hall RP 3rd, Fairley J, Woodley D, Werth VP, Hannah D, Streilein RD, McKillip J, Okawa J, Rose M, Keyes-Elstein LL, Pinckney A, Overington A, Wedgwood J, Ding L, Welch B. A multicentre randomized trial of the treatment of patients with pemphigus vulgaris with infliximab and prednisone compared with prednisone alone. Br J Dermatol. 2015 Mar;172(3):760-8. doi: 10.1111/bjd.13350. Epub 2015 Feb 5.

  PMID: 25123295 RESULT

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

MeSH Terms

Conditions

Pemphigus; Skin Diseases; Autoimmune Diseases

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Skin Diseases, Vesiculobullous; Skin and Connective Tissue Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Associate Director, Clinical Research Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Russell P. Hall, MD

  Division of Dermatology, Duke University Medical Center

  STUDY CHAIR

• E. William St. Clair, MD

  Division of Rheumatology and Immunology, Duke University Medical Center

  STUDY CHAIR

• Garnett Kelsoe, DSci

  Department of Immunology, Duke University

  PRINCIPAL INVESTIGATOR

• Victoria Werth, MD

  Department of Dermatology, University of Pennsylvania School of Medicine

  PRINCIPAL INVESTIGATOR

• Janet Fairley, MD

  Department of Dermatology, University of Iowa

  PRINCIPAL INVESTIGATOR

• David Woodley, MD

  Department of Dermatology, Norris Cancer Center, University of Southern California

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2006
• First Posted: January 30, 2006
• Study Start: March 1, 2006
• Primary Completion: December 1, 2010
• Study Completion: March 1, 2011
• Last Updated: December 6, 2017
• Results First Posted: January 31, 2013

Record last verified: 2017-11

Locations

US (4)