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Sirolimus Treatment Of Patients With SLE (STOPSLE)

Primary Purpose

Lupus Erythematosus, Systemic

Status

Not yet recruiting

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Sirolimus

Placebo

About this trial

This is an interventional treatment trial for Lupus Erythematosus, Systemic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age > 18;
Male or female;
≥ 4 ACR SLE classification criteria;
Positive ANA at a titer of ≥ 1/80;
Stable immunosuppressants (MMF ≤ 3 g/day, azathioprine ≤ 100 mg/day; methotrexate ≤ 15 mg/day) and/or antimalarials (hydroxychloroquine ≤ 400 mg/day) for 30 days prior to screening; stable oral corticosteroids for 2 weeks prior to screening; ≤ 20 mg/day prednisone or equivalent; stable belimumab for 90 days prior to screening;
BILAG 2004 index (3) level A disease activity in ≥ 1 organ/system except renal or central nervous system or (ii) BILAG 2004 index level B disease activity in ≥ 2 organs/systems if no level A disease activity is present and (iii) SLEDAI ≥ 6;
Enrollment is approved by adjudication committee.

Exclusion Criteria:

Acute SLE flare threatening vital organs;
Pregnant or lactating;
Female subjects who are planning to become pregnant during the study or within 3 months after last dosing or male subjects who are considering fathering a child within 3 months after last dosing;
Abnormal laboratory test results: hemoglobin ≤ 8 g/L (8 g/dL), platelet count ≤ 70 x 109/L (70,000 cells/mm³), white blood cell count ≤ 2.0 x 109/L (2,000 cells/mm³), neutrophils: ≤ 1.5 X 109/L, proteinuria > 3 g/day measured by 24 hour collection or spot urine protein to creatinine ratio of >3;
Glomerular filtration rate (GFR) < 50 mL/min/1.73 m², any other clinically significant abnormal screening laboratory results as evaluated by the Investigator;
Moderately serious or serious comorbidities (e.g., diabetes mellitus, congestive heart failure, chronic obstructive pulmonary disease, chronic renal insufficiency) that in investigator's opinion confers high risk for adverse events;
Patients receiving cyclophosphamide within 3 months;
Active chronic infections (e.g., HIV, hepatitis B virus, hepatitis C virus, mycobacteria); patients with oral steroid-dependent asthma;
Infections requiring intravenous antibiotics within a month or oral antibiotics within two weeks of screening;
Patients taking (unwilling or unable to stop) NAC or other antioxidants within 1 month of screening (which is considered sufficient time to revert GSH to pre-treatment levels;
Patients receiving rituximab within 12 months or other biologic therapy within five half lives;
Patients receiving mTOR inhibitors (rapamycin/sirolimus, everolimus);
Patients enrolled in other interventional trials.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Sirolimus

Placebo

Arm Description

Sirolimus 1 to 2 mg bid

Placebo 1 to 2 mg bid

Outcomes

Primary Outcome Measures

Therapeutic Benefit

Positive Response on SLE Responder Index (SRI)

Secondary Outcome Measures

Full Information

NCT ID

NCT04736953

First Posted

December 4, 2020

Last Updated

June 2, 2023

Sponsor

State University of New York - Upstate Medical University

1. Study Identification

Unique Protocol Identification Number

NCT04736953

Brief Title

Sirolimus Treatment Of Patients With SLE

Acronym

STOPSLE

Official Title

Sirolimus Treatment of Patients With Systemic Lupus Erythematosus

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

January 1, 2025 (Anticipated)

Primary Completion Date

January 1, 2029 (Anticipated)

Study Completion Date

January 1, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

State University of New York - Upstate Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

Phase II Double-blind, placebo-controlled, randomized treatment trial with two arms: one SIROLIMUS arm with 92 patients and one placebo arm with 92 patients. The safety and therapeutic efficacy of SIROLIMUS will be determined within a dosage range of 1 mg/day to 4 mg/day, which will be titrated to tolerance during an initial 3-month open label period, relative to placebo in SLE patients over 12 months followed by a 1-month washout. The proposed study design, known as an enriched enrollment randomized withdrawal (EERW), has major advantages that (1) only people who tolerate SIROLIMUS are randomized, potentially reducing the percentage of dropouts in the randomized phase and (2) it allows participants to use an individualized dosage of study medication, which mimics clinical practice in terms of how SIROLIMUS would be administered. Healthy subjects receive no drugs and serve as controls for in vitro studies.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lupus Erythematosus, Systemic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

220 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Sirolimus

Arm Type

Active Comparator

Arm Description

Sirolimus 1 to 2 mg bid

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo 1 to 2 mg bid

Intervention Type

Drug

Intervention Name(s)

Sirolimus

Other Intervention Name(s)

rapamycin

Intervention Description

Sirolimus

Intervention Type

Other

Intervention Name(s)

Placebo

Other Intervention Name(s)

Dextrose

Intervention Description

Placebo

Primary Outcome Measure Information:

Title

Therapeutic Benefit

Description

Positive Response on SLE Responder Index (SRI)

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age > 18; Male or female; ≥ 4 ACR SLE classification criteria; Positive ANA at a titer of ≥ 1/80; Stable immunosuppressants (MMF ≤ 3 g/day, azathioprine ≤ 100 mg/day; methotrexate ≤ 15 mg/day) and/or antimalarials (hydroxychloroquine ≤ 400 mg/day) for 30 days prior to screening; stable oral corticosteroids for 2 weeks prior to screening; ≤ 20 mg/day prednisone or equivalent; stable belimumab for 90 days prior to screening; BILAG 2004 index (3) level A disease activity in ≥ 1 organ/system except renal or central nervous system or (ii) BILAG 2004 index level B disease activity in ≥ 2 organs/systems if no level A disease activity is present and (iii) SLEDAI ≥ 6; Enrollment is approved by adjudication committee. Exclusion Criteria: Acute SLE flare threatening vital organs; Pregnant or lactating; Female subjects who are planning to become pregnant during the study or within 3 months after last dosing or male subjects who are considering fathering a child within 3 months after last dosing; Abnormal laboratory test results: hemoglobin ≤ 8 g/L (8 g/dL), platelet count ≤ 70 x 109/L (70,000 cells/mm³), white blood cell count ≤ 2.0 x 109/L (2,000 cells/mm³), neutrophils: ≤ 1.5 X 109/L, proteinuria > 3 g/day measured by 24 hour collection or spot urine protein to creatinine ratio of >3; Glomerular filtration rate (GFR) < 50 mL/min/1.73 m², any other clinically significant abnormal screening laboratory results as evaluated by the Investigator; Moderately serious or serious comorbidities (e.g., diabetes mellitus, congestive heart failure, chronic obstructive pulmonary disease, chronic renal insufficiency) that in investigator's opinion confers high risk for adverse events; Patients receiving cyclophosphamide within 3 months; Active chronic infections (e.g., HIV, hepatitis B virus, hepatitis C virus, mycobacteria); patients with oral steroid-dependent asthma; Infections requiring intravenous antibiotics within a month or oral antibiotics within two weeks of screening; Patients taking (unwilling or unable to stop) NAC or other antioxidants within 1 month of screening (which is considered sufficient time to revert GSH to pre-treatment levels; Patients receiving rituximab within 12 months or other biologic therapy within five half lives; Patients receiving mTOR inhibitors (rapamycin/sirolimus, everolimus); Patients enrolled in other interventional trials.

12. IPD Sharing Statement

Learn more about this trial

Sirolimus Treatment Of Patients With SLE

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