Systemic Lupus Erythematosus (SLE)Phase 2RapamuneNCT00779194
Prospective Study of Rapamycin for the Treatment of SLE
A Phase 2 study testing Rapamycin in people with Systemic Lupus Erythematosus (SLE), run by State University of New York - Upstate Medical University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Systemic Lupus Erythematosus (SLE)
- What is being tested?
- Rapamycin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 99 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to 16 Dec 2015
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
- 18 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.
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- For Healthy Control Subjects:
- 18 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.
Who cannot join
- 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.
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- 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.
- Subjects with any acute or chronic illness.
Trial locations and contacts
1 site in 1 country.
United States1 site
SUNY Upstate Medical University
Syracuse, New York, 13210
About this study
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.
Read the detailed description
43 SLE subjects and 56 healthy controls are being recruited. The study will last 1 year with 9 study visits from day 0 to day 360. The healthy controls only need to donate blood once.
The study drug, sirolimus, is taken by mouth at a starting dose of 2mg/day. The dose is adjusted to achieve blood levels in the range of 6-15 ng/ml (the levels found to be effective for preventing organ rejections).
Blood samples are obtained before taking sirolimus, every two weeks for the first month, then every three months until 1 year, and then three months later to check the effect of discontinuing rapamycin. Each SLE subject will be asked to provide up to 100 ml (20 teaspoons) of blood at each visit. The first 6 visits will take place within 3 months and the remaining 3 visits every 3 months.
Routine laboratory work will be performed. Part of the blood drawn will be used for research and part will be used for routine lab work as part of standard of care.
The non-routine laboratory studies include:
- Assessment of mitochondrial function in intact T cells
- Analysis of mTOR activity, FKBP12 expression, and global gene expression in lupus T cells.
- Predictors of therapeutic efficacy of sirolimus in SLE.
The study drug levels will be checked at every visit. The non-routine laboratory studies will be performed at Visits 0 and 8 for SLE subjects and at Visit 0 for the healthy control subjects.
Healthy control subjects will be matched by age (a decade or less), gender, and ethnic origin. They will be recruited and analyzed only for immunobiological outcomes on the same day as lupus subjects.
All subjects will sign an informed consent at visit 0. There is a separate informed consent for the main study, one for the SLE subjects and one for the Healthy Controls. The same subjects can participate in the genetic sub-study. They must sign another informed consent for the genetic sub-study, one for the SLE subjects and one for the Healthy Controls. There is no need for additional blood drawing since part of the blood drawn for the main study can be used for the genetic sub-study.
- Conditions
- Systemic Lupus Erythematosus (SLE)
- Being tested
- Rapamycin
- Medical subject headings
- Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RapamycinDrug
Also called Rapamune, Sirolimus
Rapamycin, is given to this group at a starting dose of 2 mg/day.
| Study group | Role | What they receive |
|---|---|---|
| SLE subjects | Experimental | SLE subjects receiving the study drug, Rapamune. Receives: Drug: Rapamycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year
Secondary outcomes (1)
Decrease of the Amount of Prednisone Needed to Control Disease Activity in SLE Patients.
Secondary endpoints were prednisone dose required to control disease activity.
The average daily dosage of prednisone that was employed to control disease activity was diminished from 24.3±4.7 mg/day upon enrollment at visit 1 to 7.2±2.3 mg/day upon termination of the 12-month treatment period at visit 6.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2008 (estimated)
- Study startOct 2008
- Primary completionDec 2015
- Study completion16 Dec 2015
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 (1)Papers the sponsor has linked to this study.
- Other trials for Systemic Lupus Erythematosus (SLE)Studies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 99 participants (actual)
Sponsor and investigators
- Lead sponsor
- State University of New York - Upstate Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Principal investigator, Andras Perl, State University of New York - Upstate Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00779194
- Sponsor's protocol ID
- IRB#5658
- Acronym
- Rapamune
- Status last verified
- May 2024
- First submitted
- 23 Oct 2008
- Last updated
- 12 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
Publications
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.
PubMed 29551338
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Study of Rapamycin for the Treatment of SLE
- ClinicalTrials.gov ID
- NCT00779194
- Acronym / sponsor ID
- Rapamune / IRB#5658
- Conditions
- Systemic Lupus Erythematosus (SLE)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 99 participants (actual)
- Lead sponsor
- State University of New York - Upstate Medical UniversityUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Oct 2008
- Primary completion
- Dec 2015 (actual)
- Study completion
- 16 Dec 2015 (actual)
- First posted
- 24 Oct 2008 (estimated)
- Results
- Posted 12 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
43 SLE subjects and 56 healthy controls are being recruited. The study will last 1 year with 9 study visits from day 0 to day 360. The healthy controls only need to donate blood once.
The study drug, sirolimus, is taken by mouth at a starting dose of 2mg/day. The dose is adjusted to achieve blood levels in the range of 6-15 ng/ml (the levels found to be effective for preventing organ rejections).
Blood samples are obtained before taking sirolimus, every two weeks for the first month, then every three months until 1 year, and then three months later to check the effect of discontinuing rapamycin. Each SLE subject will be asked to provide up to 100 ml (20 teaspoons) of blood at each visit. The first 6 visits will take place within 3 months and the remaining 3 visits every 3 months.
Routine laboratory work will be performed. Part of the blood drawn will be used for research and part will be used for routine lab work as part of standard of care.
The non-routine laboratory studies include:
- Assessment of mitochondrial function in intact T cells
- Analysis of mTOR activity, FKBP12 expression, and global gene expression in lupus T cells.
- Predictors of therapeutic efficacy of sirolimus in SLE.
The study drug levels will be checked at every visit. The non-routine laboratory studies will be performed at Visits 0 and 8 for SLE subjects and at Visit 0 for the healthy control subjects.
Healthy control subjects will be matched by age (a decade or less), gender, and ethnic origin. They will be recruited and analyzed only for immunobiological outcomes on the same day as lupus subjects.
All subjects will sign an informed consent at visit 0. There is a separate informed consent for the main study, one for the SLE subjects and one for the Healthy Controls. The same subjects can participate in the genetic sub-study. They must sign another informed consent for the genetic sub-study, one for the SLE subjects and one for the Healthy Controls. There is no need for additional blood drawing since part of the blood drawn for the main study can be used for the genetic sub-study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SLE subjects | Experimental | Drug: RapamycinSLE subjects receiving the study drug, Rapamune. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
- 18 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.
Key exclusion criteria (16 listed)
- 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.
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 |
|---|---|---|
| RapamycinAlso: Rapamune, SirolimusRapamycin, is given to this group at a starting dose of 2 mg/day. | Drug | SLE subjects |
Primary outcome
Reduction of the Disease Activity as Measured by SLEDAI and BILAG Scores.
Time frame: 1 year
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 secondary outcome
Decrease of the Amount of Prednisone Needed to Control Disease Activity in SLE Patients.
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 29551338Lai 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.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Rapamycin in people with Systemic Lupus Erythematosus (SLE), run by State University of New York - Upstate Medical University 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 10 inclusion and 16 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: finished, as of the sponsor's last update on 12 Jun 2024. 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 12 Jun 2024). 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?
Reduction of the Disease Activity as Measured by SLEDAI and BILAG Scores. (time frame: 1 year). 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 NCT00779194, which also lists 1 linked publication.
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 12 Jun 2024.