Prospective Study of Rapamycin for the Treatment of SLE

NCT00779194 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB#5658
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 1

Brief Summary

Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown origin. It involves multiple organs including the joints, skin, kidneys and central nervous system. The disease process is caused by a dysfunction of the immune system. The drugs currently used for the treatment of SLE are only partially effective and carry significant risks for side-effects. Patients that were resistant or intolerant to conventional medication have been effectively treated with Rapamycin and were able to decrease the amount of prednisone they needed. The purpose of this study is to prospectively determine the therapeutic efficacy and mechanism of action of Rapamune in patients with SLE. Healthy subjects not receiving Rapamune will be asked to donate blood to serve as controls only for immunobiological outcomes. As part of the research effort to understand the reason for the variations in the effects of treatment drugs by different individuals, a sub-study of the DNA makeup of subjects enrolled in the trial will also be done. The purpose of the sub-study is to possibly determine whether different responses to the drugs used to treat SLE have a correlation with the differences in the genetic makeup of the subjects.

Conditions

Systemic Lupus Erythematosus (SLE)

Outcome Measures

Primary Outcomes (1)

• Reduction of the Disease Activity as Measured by SLEDAI and BILAG Scores.

  The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and The British Isles Lupus Assessment Group (BILAG) are clinical tools for assessing disease activity in lupus erythematosus patients. These indices play a central role as core determinants in SLE Responder Index. SLEDAI, comprising 24 items, quantifies disease activity on a scale of 0 to 105. Higher scores indicate more severe disease activity, reflecting cumulative impact of clinical and laboratory variables. BILAG, a comprehensive assessment, encompasses 97 items organized into 9 organ domains. The scoring ranges from A to E: A: No activity B: Mild activity C: Moderate activity D: Severe activity E: Very severe activity Total BILAG score is sum of individual item scores across all domains, with a potential range from 0 (if all items are graded as A, denoting no activity) to 97 (if all items are graded as E, signifying very severe activity). A lower total BILAG score indicates less severe disease activity.

  1 year

Secondary Outcomes (1)

• Decrease of the Amount of Prednisone Needed to Control Disease Activity in SLE Patients.

  1 year

Study Arms (1)

SLE subjects

EXPERIMENTAL

SLE subjects receiving the study drug, Rapamune.

Drug: Rapamycin

Interventions

Rapamycin DRUG

Rapamycin, is given to this group at a starting dose of 2 mg/day.

Also known as: Rapamune, Sirolimus

SLE subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For SLE Subjects:
• SLE patients who exhibit ongoing disease activity by SLEDAI greater or equal to 4.
• SLE patients whose disease activity is controlled by administration of corticosteroids, most commonly, at least 10 mg/day of prednisone.
• years of age or older.
• Updated vaccinations prior to study entry.
• Use of effective contraception for male patients before, during and up to 12 weeks after sirolimus therapy.
• For Healthy Control Subjects:
• years of age or older
• Must be matched with one of the SLE patients enrolled in the study by age, gender and ethnic origin
• Must not have any acute or chronic illness.

You may not qualify if:

• For SLE Subjects:
• Patients who are pregnant.
• Patients with allergy or intolerance to sirolimus.
• Patients with life-threatening manifestations of SLE.
• Patients with proteinuria exceeding 500 mg/24 h or urine protein/creatine ratio \>0.5.
• Patients with total cholesterol \> 300 mg/dl or triglyceride \> 400 mg.dl will be excluded.
• Patients with acute infection requiring antibiotics.
• Patients on sirolimus who develop infections and require intravenous antibiotics and fail to show clinical improvement in 5 days.
• Patients concurrently undergoing B cell-depleting therapy, cyclophosphamide, cyclosporine, and tacrolimus.
• Patients who have received investigational biologic B-cell depleting products within one year of study initiation.
• Patients with a history of chronic viral infections (e.g., HIV, hepatitis B, hepatitis C) or with a history of a malignancy (except non-melanoma skin cancer).
• Due to interference with sirolimus metabolism, subjects will not be allowed to receive concomitant rifampin, ketoconazole,voriconazole, itraconazole, erythromycin, or clarithromycin during the study.
• Patients with any type of interstitial lung disease.
• For Healthy control Subjects:
• Subjects who are pregnant.

Sponsors & Collaborators

• State University of New York - Upstate Medical University: lead
• Pfizer: collaborator

Study Sites (1)

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Related Publications (1)

• Lai ZW, Kelly R, Winans T, Marchena I, Shadakshari A, Yu J, Dawood M, Garcia R, Tily H, Francis L, Faraone SV, Phillips PE, Perl A. Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1/2 trial. Lancet. 2018 Mar 24;391(10126):1186-1196. doi: 10.1016/S0140-6736(18)30485-9. Epub 2018 Mar 15.

  PMID: 29551338 RESULT

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Andras Perl
• Organization: STATE UNIVERSITY OF NEW YORK

perla@upstate.edu

3154644194

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Division Chief of Rheumatology

Study Record Dates

• First Submitted: October 23, 2008
• First Posted: October 24, 2008
• Study Start: October 1, 2008
• Primary Completion: December 1, 2015
• Study Completion: December 16, 2015
• Last Updated: June 12, 2024
• Results First Posted: June 12, 2024

Record last verified: 2024-05

Locations

US (1)