PemphigusEarly Phase 1NCT01313923
Evaluating Sirolimus to Treat Autoimmune Blistering Dermatosis Pemphigus
A Early Phase 1 study testing Sirolimus (formerly known as Rapamycin) in people with Pemphigus, run by University of California, Irvine at 1 site in United States.
Trial summary
The purpose of this research is to study alternative treatments for the skin disease pemphigus (a rare autoimmune blistering disorder of the skin) by using sirolimus, an immunosuppressive drug. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pemphigus
- What is being tested?
- Sirolimus (formerly known as Rapamycin)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2011to Oct 2014
- Phase
- Early Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must be 18 years of age or older.
- Subject must have an established diagnosis of pemphigus disorder via biopsy and/or serologic titer, as determined appropriate by the lead researcher.
- Subject must have active disease at the time of enrollment, as defined by a positive Nikolsky sign.
- Subject must not be taking any immunosuppressive medication or therapy other than corticosteroids.
- Subject must be able to understand and follow directions.
- If female, subject is not currently breast feeding and/or pregnant as confirmed via negative pregnancy test, no potential for pregnancy, or if of child-bearing age, agrees to using birth control for entire duration of study and 12 weeks after end of study.
Who cannot join
- Subject may not be under 18 years old.
- Subject cannot understand or follow directions.
- Subject may not have any condition that could, in the opinion of the investigator, compromise the subject's ability to give written consent and/or comply with the study procedures, such as a history of substance abuse or a psychiatric condition.
- If female and of child bearing age, is pregnant or unwilling to use birth control during the study period.
- Subject may not have any of the following laboratory abnormalities at baseline:
- total white blood cell count < 2,000/mm3 or platelet count < 100,000/mm3
Show all 21Show fewer
- creatinine >1.5mg/dL
- urine analysis protein of 2+ or greater
- fasting triglycerides > 400 mg/dL, fasting total cholesterol > 300 mg/dL, or fasting LDLcholesterol > 160 mg/dL
- transaminases > 2 times the upper limit of normal
- Subjects may not be using any of the following medications: systemic antifungals, antiepileptics, HIV protease inhibitors, cimetidine, cisapride, clarithromycin, danazol, diltiazem, erythromycin, metoclopramide, rifabutin, rifampin, rifapentine, troleandomycin, or verapamil
- Subject may not consume grapefruit juice and/or St. John's Wort (hypericum perforatum) throughout the duration of the study.
- Subject may not have other significant concurrent medical conditions, including
- Active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma, or history of cancer (other than fully resected and surgically cured cutaneous basal cell and squamous cell carcinoma) within 5 years before the first 13 of 25 sirolimus dose. If malignancy occurred more than 5 years ago, documentation of disease-free state since treatment is required.
- Known immunodeficiency syndromes, including HIV
- Renal failure or insufficiency, as defined by laboratory parameters above
- Significant proteinuria, as defined by laboratory parameters above
- History of high cholesterol, lipids, or liver disease, as defined by laboratory parameters above
- Uncontrolled hypertension, as defined by a blood pressure > 140/90 despite optimal medical therapy, as prescribed by primary care doctor
- Any condition that, in the opinion of the investigator, might cause this study to be detrimental to the subject
- Any active Common Terminology Criteria (CTC) grade 2 (localized infection; requiring local intervention) or higher infection (including chronic or localized infections) within 30 days prior to screening, at screening, or during screening period prior to first dose of sirolimus
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, Irvine
Irvine, California, 92697
About this study
Official title: Evaluation of Sirolimus for the Treatment of the Autoimmune Blistering Dermatosis Pemphigus
The purpose of this research is to study alternative treatments for the skin disease pemphigus (a rare autoimmune blistering disorder of the skin) by using sirolimus, an immunosuppressive drug. Immunosuppressive drugs inhibit or prevent the activity of the immune system and are commonly used to treat autoimmune diseases, inflammatory diseases, and organ transplantation rejection.
Read the detailed description
The purpose of this study is to explore a new medication for the skin disease termed pemphigus. Our specific aim is to determine whether the use of sirolimus will allow for a decrease in the dosage or possibly eliminate the need for corticosteroids, which so far is the only type of drug that can control this disease.
Pemphigus is an autoimmune disease characterized by blistering, caused by autoantibodies against certain cells in the skin. This disease most commonly occurs in individuals ages 50 and older, and it presents as painful shallow erosions and/or blisters in the mouth and/or skin. Pemphigus is very painful and uncomfortable, associated with impaired quality of life and significant morbidity. Severe or untreated cases of pemphigus can become fatal if the involved surface area becomes large enough to cause dehydration and/or infection. The first line of therapy, and the standard of care, for pemphigus remain to be systemic corticosteroids. However, corticosteroids have many known side effects, especially when used for a long time. Many cases of pemphigus are insufficiently controlled with corticosteroids alone and require the addition of other immunosuppressive agents, such as azathioprine, cyclophosphamide, mycophenolate mofetil, or a variety of other therapies used off-label. All of these treatments are not always successful and have undesirable side effects, including increased risk of malignancy and infections. Although these treatments can offer some relief from the disease, they are also often the cause of many side effects.
Sirolimus (formerly known as rapamycin) is a drug commonly used after renal transplants to prevent organ rejection. In this study, pemphigus subjects with active disease will begin taking sirolimus in conjunction with corticosteroids, using a similar regimen used for organ transplantation to treat pemphigus. While increasing sirolimus and decreasing the corticosteroids, subjects will be monitored over a 12 month period to evaluate their disease response. The purpose of this study is to observe data trends.
Our specific aim is to determine whether the use of sirolimus will allow for a decrease in the dosage of the corticosteroid prednisone, which so far is the only type of drugs that can control these diseases, without making the pemphigus worse.
- Conditions
- Pemphigus
- Being tested
- Sirolimus (formerly known as Rapamycin)
- Keywords
- Pemphigus
- Medical subject headings
- Pemphigus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sirolimus (formerly known as Rapamycin)Drug
Also called Sirolimus, Rapamycin
For low to moderate immunologic risk, the loading dose is 6mg immediately after transplantation, followed by 2mg PO Qday in conjunction with cyclosporine and corticosteroids. After 2-4 months, cyclosporine should be discontinued over 4-8 weeks while titrating sirolimus drug concentrations within the target-range with whole blood trough concentrations every 1-2 weeks. Monitoring is needed because cyclosporine inhibits the metabolism of sirolimus, and discontinuation of cyclosporine can lead to lower levels of sirolimus. In high immunologic risk patients, the loading dose is 15mg after transplantation, followed by 5mg PO Qday in conjunction with cyclosporine and corticosteroids for 12 months. A whole blood trough level is recommended between days 5 and 7 with adjustment to the daily dose.
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus (formerly known as Rapamycin) | Experimental | Subjects with stable pemphigus vulgaris already on treatment with prednisone will be enrolled. Subjects will start taking oral sirolimus and have it up-titrated while decreasing the prednisone dosage. Their disease state will be monitored during this time. Receives: Drug: Sirolimus (formerly known as Rapamycin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement of ABSIS Score While Reducing Steroid Dosage
Measurement of disease severity will be quantified using ABSIS (Autoimmune Bullous Skin Disorder Intensity Score). Improvement in disease control is quantified by the maintenance or improvement of ABSIS score while reducing steroid dosage.
No results as study has been terminated early by the investigator.
Measured: Expected time line 24 months
Secondary outcomes (1)
Statistical Measures
The statistical goal is to observe "success," an improvement in disease control while up-titrating sirolimus dosage. As there will be no control group, the subject or progress at the end of the study will be compared to their baseline at the beginning of the study. The subject and disease severity at the beginning of the study will be compared to the disease severity at each visit and be correlated with the dosage of sirolimus and corticosteroid. However, since no patient completed the study, the outcome and any data collected was not assessed.
Measured: Study early termination by investigator - no participant completed any visits of the study - no measurements taken
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2011 (estimated)
- Study startFeb 2011
- Primary completionOct 2014
- Study completionOct 2014
Why it stopped: Lack of funding
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.
- Other trials for PemphigusStudies of the same condition, open and under way.
- More trials run by University of California, IrvineThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Irvine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sergei Grando, University of California, Irvine
- Investigators
- Sergei Grando, MD, PhD, Principal investigator, University of California, Irvine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01313923
- Sponsor's protocol ID
- 2010-7844
- Status last verified
- May 2017
- First submitted
- 10 Mar 2011
- Last updated
- 9 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Sirolimus for the Treatment of the Autoimmune Blistering Dermatosis Pemphigus
- ClinicalTrials.gov ID
- NCT01313923
- Acronym / sponsor ID
- 2010-7844
- Conditions
- Pemphigus
- Keywords
- Pemphigus
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of funding
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of California, IrvineUniversity, hospital or other
- Study start
- Feb 2011
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 14 Mar 2011 (estimated)
- Results
- Posted 25 Mar 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 research is to study alternative treatments for the skin disease pemphigus (a rare autoimmune blistering disorder of the skin) by using sirolimus, an immunosuppressive drug. Immunosuppressive drugs inhibit or prevent the activity of the immune system and are commonly used to treat autoimmune diseases, inflammatory diseases, and organ transplantation rejection.
Detailed description
The purpose of this study is to explore a new medication for the skin disease termed pemphigus. Our specific aim is to determine whether the use of sirolimus will allow for a decrease in the dosage or possibly eliminate the need for corticosteroids, which so far is the only type of drug that can control this disease.
Pemphigus is an autoimmune disease characterized by blistering, caused by autoantibodies against certain cells in the skin. This disease most commonly occurs in individuals ages 50 and older, and it presents as painful shallow erosions and/or blisters in the mouth and/or skin. Pemphigus is very painful and uncomfortable, associated with impaired quality of life and significant morbidity. Severe or untreated cases of pemphigus can become fatal if the involved surface area becomes large enough to cause dehydration and/or infection. The first line of therapy, and the standard of care, for pemphigus remain to be systemic corticosteroids. However, corticosteroids have many known side effects, especially when used for a long time. Many cases of pemphigus are insufficiently controlled with corticosteroids alone and require the addition of other immunosuppressive agents, such as azathioprine, cyclophosphamide, mycophenolate mofetil, or a variety of other therapies used off-label. All of these treatments are not always successful and have undesirable side effects, including increased risk of malignancy and infections. Although these treatments can offer some relief from the disease, they are also often the cause of many side effects.
Sirolimus (formerly known as rapamycin) is a drug commonly used after renal transplants to prevent organ rejection. In this study, pemphigus subjects with active disease will begin taking sirolimus in conjunction with corticosteroids, using a similar regimen used for organ transplantation to treat pemphigus. While increasing sirolimus and decreasing the corticosteroids, subjects will be monitored over a 12 month period to evaluate their disease response. The purpose of this study is to observe data trends.
Our specific aim is to determine whether the use of sirolimus will allow for a decrease in the dosage of the corticosteroid prednisone, which so far is the only type of drugs that can control these diseases, without making the pemphigus worse.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sirolimus (formerly known as Rapamycin) | Experimental | Drug: Sirolimus (formerly known as Rapamycin)Subjects with stable pemphigus vulgaris already on treatment with prednisone will be enrolled. Subjects will start taking oral sirolimus and have it up-titrated while decreasing the prednisone dosage. Their disease state will be monitored during this time. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Subject must be 18 years of age or older.
- Subject must have an established diagnosis of pemphigus disorder via biopsy and/or serologic titer, as determined appropriate by the lead researcher.
- Subject must have active disease at the time of enrollment, as defined by a positive Nikolsky sign.
- Subject must not be taking any immunosuppressive medication or therapy other than corticosteroids.
- Subject must be able to understand and follow directions.
Key exclusion criteria (21 listed)
- Subject may not be under 18 years old.
- Subject cannot understand or follow directions.
- Subject may not have any condition that could, in the opinion of the investigator, compromise the subject's ability to give written consent and/or comply with the study procedures, such as a history of substance abuse or a psychiatric condition.
- If female and of child bearing age, is pregnant or unwilling to use birth control during the study period.
- Subject may not have any of the following laboratory abnormalities at baseline:
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 |
|---|---|---|
| Sirolimus (formerly known as Rapamycin)Also: Sirolimus, RapamycinFor low to moderate immunologic risk, the loading dose is 6mg immediately after transplantation, followed by 2mg PO Qday in conjunction with cyclosporine and corticosteroids. After 2-4 months, cyclosporine should be discontinued over 4-8 weeks while titrating sirolimus drug concentrations within the target-range with whole blood trough concentrations every 1-2 weeks. Monitoring is needed because cyclosporine inhibits the metabolism of sirolimus, and discontinuation of cyclosporine can lead to lower levels of sirolimus. In high immunologic risk patients, the loading dose is 15mg after transplantation, followed by 5mg PO Qday in conjunction with cyclosporine and corticosteroids for 12 months. A whole blood trough level is recommended between days 5 and 7 with adjustment to the daily dose. | Drug | Sirolimus (formerly known as Rapamycin) |
Primary outcome
Improvement of ABSIS Score While Reducing Steroid Dosage
Time frame: Expected time line 24 months
Measurement of disease severity will be quantified using ABSIS (Autoimmune Bullous Skin Disorder Intensity Score). Improvement in disease control is quantified by the maintenance or improvement of ABSIS score while reducing steroid dosage. No results as study has been terminated early by the investigator.
1 secondary outcome
Statistical Measures
Time frame: Study early termination by investigator - no participant completed any visits of the study - no measurements taken
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Sergei Grando, MD, PhD principal investigator
University of California, Irvine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Sirolimus (formerly known as Rapamycin) in people with Pemphigus, run by University of California, Irvine 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 6 inclusion and 21 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 9 Jun 2017. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 25 Mar 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?
Improvement of ABSIS Score While Reducing Steroid Dosage (time frame: Expected time line 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jun 2017.