Evaluating Sirolimus to Treat Autoimmune Blistering Dermatosis Pemphigus

NCT01313923 | Terminated Early Phase 1 Results

• 1 other identifier: 2010-7844
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Pemphigus

Keywords

Pemphigus

Outcome Measures

Primary Outcomes (1)

• 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.

  Expected time line 24 months

Secondary Outcomes (1)

• Statistical Measures

  Study early termination by investigator - no participant completed any visits of the study - no measurements taken

Study Arms (1)

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.

Drug: Sirolimus (formerly known as Rapamycin)

Interventions

Sirolimus (formerly known as Rapamycin) DRUG

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.

Also known as: Sirolimus, Rapamycin

Sirolimus (formerly known as Rapamycin)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of California, Irvine: lead

Study Sites (1)

University of California, Irvine

Irvine, California, 92697, United States

Location

MeSH Terms

Conditions

Pemphigus

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

No results as study has been terminated early by the investigator.

Results Point of Contact

• Title: Sergei A. Grando, MD, PhD, DSc
• Organization: UC Irvine Dermatology Research Center

sgrando@uci.edu

9498242713

Study Officials

• Sergei Grando, MD, PhD

  University of California, Irvine

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: March 10, 2011
• First Posted: March 14, 2011
• Study Start: February 1, 2011
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: June 9, 2017
• Results First Posted: March 25, 2016

Record last verified: 2017-05

Locations

US (1)