Use of Infliximab for the Treatment of Pemphigus Vulgaris

NCT ID: NCT00283712

Last Updated: 2017-12-06

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-03-31

Study Completion Date

2011-03-31

Brief Summary

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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.

Detailed Description

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PV involves blistering of the outer layer of skin and mucous membranes, causing a separation of epidermal cells. The disease occurs when the immune system produces antibodies to specific proteins in the skin and mucous membranes; the cause for production of these autoantibodies is unknown. Infliximab is a genetically engineered monoclonal antibody directed against tumor necrosis factor (TNF)-alpha, a chemical messenger that activates an immune response. Infliximab has been used to treat other autoimmune disorders, including rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease. This study will evaluate the safety and efficacy of infliximab given in combination with prednisone for the treatment of adults with PV.

This study will last 26 weeks. At study entry, all patients will be taking a stable dose of prednisone (or an equivalent corticosteroid) of 20 to 120 mg/day for at least 2 weeks prior to study entry. Patients will be randomly assigned to one of two arms: experimental or placebo comparator. The experimental treatment arm will receive infusions of infliximab, and the control arm will receive placebo. Infusions will be given at study entry and Weeks 2, 6, and 14. Before the start of each infusion, a physical exam, vital signs measurement, medical and medication history, review of a disease activity log, a skin evaluation, and blood collection will occur. During each infusion and for 1 hour postinfusion, patients' vital signs will be monitored for any adverse events. Patients will need a responsible adult to take them home after they are discharged from the treatment facility; this person should remain with the patient overnight in case any problems arise from the treatment. The patient will be contacted by phone that night and the next morning after infusion and will be asked about any adverse effects they may have experienced. Those patients that experience adverse effects may be asked to return to the treatment facility for examination. Prednisone doses may be tapered by 15 percent every 2 weeks during the study at the investigator's discretion.

There will be a total of 9 study visits until Week 26: screening, study entry, Week 2, and every 4 weeks thereafter. Each study visit will include a physical exam, vital signs measurement, medical and medication history, a review of the disease activity log and adverse events experienced since the last visit, skin assessments, and blood collection; patients will also be asked to complete a tuberculosis (TB) questionnaire. Patients will be asked to complete quality of life questionnaires at study entry and Weeks 10, 18, and 26. Skin biopsies of unaffected skin will be done at study entry and Weeks 10, 18, and 26; if patients have PV-associated lesions, additional skin biopsies of affected skin will be done at study entry and Week 18.

Conditions

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Pemphigus

Keywords

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Skin Diseases Autoimmune Diseases

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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Infliximab

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.

Group Type EXPERIMENTAL

Infliximab

Intervention Type 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

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.

Group Type PLACEBO_COMPARATOR

Placebo Comparator

Intervention Type OTHER

Placebo administered in place of infliximab for control group

Interventions

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Infliximab

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

Intervention Type DRUG

Placebo Comparator

Placebo administered in place of infliximab for control group

Intervention Type OTHER

Other Intervention Names

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Remicade® Control Arm

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Autoimmunity Centers of Excellence

OTHER

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Russell P. Hall, MD

Role: STUDY_CHAIR

Division of Dermatology, Duke University Medical Center

E. William St. Clair, MD

Role: STUDY_CHAIR

Division of Rheumatology and Immunology, Duke University Medical Center

Garnett Kelsoe, DSci

Role: PRINCIPAL_INVESTIGATOR

Department of Immunology, Duke University

Victoria Werth, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Dermatology, University of Pennsylvania School of Medicine

Janet Fairley, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Dermatology, University of Iowa

David Woodley, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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Norris Cancer Center, University of Southern California

Los Angeles, California, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 15243495 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14973643 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16086769 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16029365 (View on PubMed)

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.

Reference Type RESULT
PMID: 25123295 (View on PubMed)

Related Links

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https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID)

https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation (DAIT)

Other Identifiers

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DAIT APV01

Identifier Type: -

Identifier Source: org_study_id