Pemphigus VulgarisPhase 2NCT00483119
Randomized Trial of IVIg With or Without Cyclophosphamide in Pemphigus
A Phase 2 study testing intravenous immunoglobulin and cyclophosphamide in people with Pemphigus Vulgaris, run by NYU Langone Health at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Pemphigus Vulgaris
- What is being tested?
- intravenous immunoglobulin and cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2007to Feb 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
Show all 14Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Pemphigus Vulgaris
- Being tested
- intravenous immunoglobulin, cyclophosphamide
- Keywords
- pemphigus vulgaris, IVIg, cyclophosphamide, treatment, pemphigus antibodies
- Medical subject headings
- Pemphigus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
intravenous immunoglobulinDrug
Also called IVIg, Gamunex
Gamunex 10% 500/mg/kg/day x four days per cycle total of four cycles
cyclophosphamideDrug
Also called CP
cyclophosphamide dose of 2mg/kg/day divided into three-times daily oral administration
| Study group | Role | What they receive |
|---|---|---|
| Group A | Active comparator | IVIg alone (intravenous immunoglobulin) Receives: Drug: intravenous immunoglobulin |
| Group B | Experimental | IVIg with cyclophosphamide Receives: Drug: intravenous immunoglobulin; Drug: cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Outcome: Extent and Severity of Disease
Measured: 6 - 10 weeks after initiation of therapy
Serum Levels of Pemphigus Antibodies
Measured: 6-10 weeks after initiation of therapy
Secondary outcomes (2)
Toxicity of Treatment: Measured in Renal Toxicity, Myelosuppression or Hepatic Toxicity
Measured: Throughout course of study
Ability to be Weaned Off Steroids
Measured: Measured 6 and 10 weeks after initiation of IVIg treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2007 (estimated)
- Study startApr 2007
- Primary completionFeb 2010
- Study completionFeb 2011
Why it stopped: Study was terminated due to the death of the PI.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Pemphigus VulgarisStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean-Claude Bystryn, M.D., Principal investigator, NYU MEDICAL CENTER
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00483119
- Sponsor's protocol ID
- 3343
- Status last verified
- Jan 2016
- First submitted
- 5 Jun 2007
- Last updated
- 18 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Green MG, Bystryn JC. Effect of intravenous immunoglobulin therapy on serum levels of IgG1 and IgG4 antidesmoglein 1 and antidesmoglein 3 antibodies in pemphigus vulgaris. Arch Dermatol. 2008 Dec;144(12):1621-4. doi: 10.1001/archdermatol.2008.503.
PubMed 19075146Czernik A, Bystryn JC. Kinetics of response to conventional treatment in patients with pemphigus vulgaris. Arch Dermatol. 2008 May;144(5):682-3. doi: 10.1001/archderm.144.5.682. No abstract available.
PubMed 18490602Czernik A, Beutner EH, Bystryn JC. Intravenous immunoglobulin selectively decreases circulating autoantibodies in pemphigus. J Am Acad Dermatol. 2008 May;58(5):796-801. doi: 10.1016/j.jaad.2008.01.007.
PubMed 18423257Czernik A, Bystryn JC. Improvement of intravenous immunoglobulin therapy for bullous pemphigoid by adding immunosuppressive agents: marked improvement in depletion of circulating autoantibodies. Arch Dermatol. 2008 May;144(5):658-61. doi: 10.1001/archderm.144.5.658.
PubMed 18490594
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Randomized Trial of IVIg With or Without Cyclophosphamide in Pemphigus
- ClinicalTrials.gov ID
- NCT00483119
- Acronym / sponsor ID
- 3343
- Conditions
- Pemphigus Vulgaris
- Keywords
- pemphigus vulgaris, IVIg, cyclophosphamide, treatment, pemphigus antibodies
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to the death of the PI.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- Apr 2007
- Primary completion
- Feb 2010 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 6 Jun 2007 (estimated)
- Results
- Posted 18 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Active comparator | Drug: intravenous immunoglobulinIVIg alone (intravenous immunoglobulin) |
| Group B | Experimental | Drug: intravenous immunoglobulin, Drug: cyclophosphamideIVIg with cyclophosphamide |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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:
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| intravenous immunoglobulinAlso: IVIg, GamunexGamunex 10% 500/mg/kg/day x four days per cycle total of four cycles | Drug | Group A, Group B |
| cyclophosphamideAlso: CPcyclophosphamide dose of 2mg/kg/day divided into three-times daily oral administration | Drug | Group B |
Primary outcome
Clinical Outcome: Extent and Severity of Disease
Time frame: 6 - 10 weeks after initiation of therapy
Serum Levels of Pemphigus Antibodies
Time frame: 6-10 weeks after initiation of therapy
2 secondary outcomes
Toxicity of Treatment: Measured in Renal Toxicity, Myelosuppression or Hepatic Toxicity
Time frame: Throughout course of study
Ability to be Weaned Off Steroids
Time frame: Measured 6 and 10 weeks after initiation of IVIg treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19075146Green MG, Bystryn JC. Effect of intravenous immunoglobulin therapy on serum levels of IgG1 and IgG4 antidesmoglein 1 and antidesmoglein 3 antibodies in pemphigus vulgaris. Arch Dermatol. 2008 Dec;144(12):1621-4. doi: 10.1001/archdermatol.2008.503.
- Background: PubMed 18490602Czernik A, Bystryn JC. Kinetics of response to conventional treatment in patients with pemphigus vulgaris. Arch Dermatol. 2008 May;144(5):682-3. doi: 10.1001/archderm.144.5.682. No abstract available.
- Background: PubMed 18423257Czernik A, Beutner EH, Bystryn JC. Intravenous immunoglobulin selectively decreases circulating autoantibodies in pemphigus. J Am Acad Dermatol. 2008 May;58(5):796-801. doi: 10.1016/j.jaad.2008.01.007.
- Background: PubMed 18490594Czernik A, Bystryn JC. Improvement of intravenous immunoglobulin therapy for bullous pemphigoid by adding immunosuppressive agents: marked improvement in depletion of circulating autoantibodies. Arch Dermatol. 2008 May;144(5):658-61. doi: 10.1001/archderm.144.5.658.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-Claude Bystryn, M.D. principal investigator
NYU MEDICAL CENTER
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing intravenous immunoglobulin and cyclophosphamide in people with Pemphigus Vulgaris, run by NYU Langone Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Outcome: Extent and Severity of Disease (time frame: 6 - 10 weeks after initiation of therapy). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00483119, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Feb 2016.