Randomized Trial of IVIg With or Without Cyclophosphamide in Pemphigus

January 21, 2016 updated by: NYU Langone Health

Phase 2 Randomized Trial of IVIg With or Without Cyclophosphamide in Pemphigus

The purpose of this study is to compare two standard treatments for pemphigus to determine which more effectively improves the clinical manifestations of the disease and decreases serum level of the autoantibodies which cause the disease.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Pemphigus is a serious and life-threatening autoimmune disease characterized by blisters and erosions that occur on the skin and oral mucosa. It is caused by autoantibodies that attack desmoglein 1 and 3, adhesion molecules that are present on the surface of the cells (keratinocytes) that make up the superficial layer of the skin. As a result these cells stop sticking together, and come apart resulting in the formation of blisters on the skin.

Pemphigus is usually treated with systemic corticosteroids often given together with immunosuppressive drugs such as Cytoxan (cyclophosphamide), Imuran (azathioprine), methotrexate, CellCept (mycophenolate mofetil) and others. However, the prolonged and high doses of systemic steroids and other immunosuppressive agents used to treat the disease are associated with significant toxicity.

A new treatment which is now being used to treat pemphigus patients that are unresponsive, or that have developed complications to conventional treatment is IVIg (intravenous immunoglobulin). IVIg consists of one of the protein fractions present in blood. It is the fraction that contains antibodies and is called immunoglobulin (Ig). It is purified from blood that has been collected from thousands of donors and treated to remove potential infectious agents. It is administered intravenously (IV) over several hours, several days in succession. The cycles are usually repeated every 2 to 4 weeks until the disease is controlled.

IVIg treatment is currently given in either of two ways, either by itself or with an immunosuppressive drug such as cyclophosphamide or azathioprine. It is unknown which of these two procedures is better. This trial is being conducted to determine which treatment is more effective.

The trial is being conducted in patients with pemphigus that are not responding to, or have developed complications from, standard treatment. All patients will be treated with IVIg administered using a standard protocol. The IVIg will be given daily for 4 days, and this cycle will be repeated every other week for a total of 4 cycles. In addition, half of the patients will be selected by chance to also be treated with cyclophosphamide, an immunosuppressive drug often used to treat other autoimmune diseases including pemphigus. The cyclophosphamide is a pill that is taken 3 times a day. A total of 12 patients will be treated in each arm of the trial. The trial is being conducted by Dr. Jean-Claude Bystryn at the New York University Medical Center.

The extent and activity of the disease, as well as the blood levels of pemphigus antibodies, will be measured at baseline prior to entry into the trial and periodically during the trial.

The goal of the study is to determine whether there is a difference between the two treatments in the rate at which: 1) the activity and extent of the disease improves, 2) the dose of corticosteroids required to treat the disease can be reduced, and 3) the blood level of pemphigus antibodies decrease.

This trial will test this hypothesis by examining whether IVIg treatment given with cyclophosphamide results in a more rapid decline in circulating pemphigus antibodies than when given alone.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10016
        • NYU Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 83 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Lesions consistent with pemphigus foliaceus or vulgaris
  • Diagnosis confirmed by histology and IIF ≥ 40 within past month
  • On ≥20mg/day of prednisone per day for two weeks or ≥ 80mg/day for one week
  • Women of childbearing potential negative HCG obtained two weeks prior to first IVIg
  • Agrees to two acceptable forms of contraception* if randomized to cyclophosphamide group:
  • IUD (except progesterone T), Combination oral contraceptives, transdermal patch, vaginal ring, hormonal injectables or implantables, male latex condom, diaphragm, cervical cap, or vaginal sponge (contains spermicide)
  • Normal organ function confirmed by CBC, UA, LFTs and Ig levels within defined inclusion criteria
  • Responds yes to at least one of the criteria below:
  • Persistence of clinical manifestations of disease despite steroid treatment
  • Flare in disease activity after an attempt at steroid tapering
  • Failure of established lesions to heal
  • Rapidly progressive disease.
  • Conventional therapy is relatively contraindicated i.e. side effects, co-morbid conditions
  • systemic infections, peptic ulcers, osteoporosis, hypertension, cataracts or others

Exclusion Criteria:

  • Use of IVIg within past 3 weeks or the use of a cytotoxic drug within the past 2 weeks
  • Participating in another clinical trial at the time of screening and enrollment
  • Medical condition that precludes use of IVIg or cyclophosphamide (i.e. pregnancy breastfeeding, underlying chronic infection, concurrent opportunistic infection, sepsis or volume depletion
  • Renal insufficiency ( GFR <90, proteinuria (>1+, x 2), creatinine >1.8 or increased WBC or RBCs which cannot be explained by cystitis.)
  • Known hypersensitivity to study drugs, IVIg or cyclophosphamide

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Group A
IVIg alone (intravenous immunoglobulin)
Drug: intravenous immunoglobulin
Gamunex 10% 500/mg/kg/day x four days per cycle total of four cycles
Other Names:
  • Gamunex
  • IVIg
Experimental: Group B
IVIg with cyclophosphamide
Drug: intravenous immunoglobulin
Gamunex 10% 500/mg/kg/day x four days per cycle total of four cycles
Other Names:
  • Gamunex
  • IVIg
Drug: cyclophosphamide
cyclophosphamide dose of 2mg/kg/day divided into three-times daily oral administration
Other Names:
  • CP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Clinical Outcome: Extent and Severity of Disease
Time Frame: 6 - 10 weeks after initiation of therapy
6 - 10 weeks after initiation of therapy
Serum Levels of Pemphigus Antibodies
Time Frame: 6-10 weeks after initiation of therapy
6-10 weeks after initiation of therapy

Secondary Outcome Measures

Outcome Measure
Time Frame
Toxicity of Treatment: Measured in Renal Toxicity, Myelosuppression or Hepatic Toxicity
Time Frame: Throughout course of study
Throughout course of study
Ability to be Weaned Off Steroids
Time Frame: Measured 6 and 10 weeks after initiation of IVIg treatment
Measured 6 and 10 weeks after initiation of IVIg treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NYU Langone Health

Investigators

  • Principal Investigator: Jean-Claude Bystryn, M.D., NYU Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2007

Primary Completion (Actual)

February 1, 2010

Study Completion (Actual)

February 1, 2011

Study Registration Dates

First Submitted

June 5, 2007

First Submitted That Met QC Criteria

June 5, 2007

First Posted (Estimate)

June 6, 2007

Study Record Updates

Last Update Posted (Estimate)

February 18, 2016

Last Update Submitted That Met QC Criteria

January 21, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3343

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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