Lupus Erythematosus, Systemic
Conditions
Brief summary
The primary objective of the study is to evaluate the safety, tolerability, and efficacy of 4 weeks intravenous treatment with Cpn10 in subjects with mild to moderate active SLE.
Interventions
BIOLOGICALAla-Cpn10
DRUGPlacebo
Sponsors
Invion, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
(ALL must be met): To be entered on study, subjects must meet the following criteria: 1. Male or female 2. Age 18 - 75 years 3. Patients fulfilling at least 4 criteria for SLE as defined by the American College of Rheumatology (ACR) 4. Laboratory values as follows: Documented ANA titer ≥ 1:160 or positive anti-dsDNA antibodies at, or any time prior to screening (verifiable laboratory result) 5. Not pregnant or breast-feeding 6. If corticosteroids are required for disease stability prior to study entry, able to tolerate a stable dose of ≤ 0.3 mg/kg/day of prednisone or equivalent for the duration of the study. 7. Agreement to use an effective form of contraception for the duration of the study. 8. Ability to understand and give consent. 9. Willing to participate and able to comply with the study requirements, procedures and visits. Mild SLE only 10. Present with mild active SLE disease Moderate SLE only 11. Present with active SLE disease based on SLE disease activity score (SLEDAI) ≥4 and ≤10 12. MCP-1 urinary level \> 35 pg/ml 13. IL-6 serum level \> 10 pg/ml 14. Meets the American College of Rheumatology (ACR) conditions for renal disorder as one of the diagnostic criteria for SLE i.e. 1. Persistent proteinuria between 0.5 and 1.0 grams per day or \> than 3+ by dipstick OR 2. Cellular casts--may be red cell, hemoglobin, granular, tubular, or mixed OR 15. Physician (Pathologist) diagnosis of lupus nephritis of no greater severity than: 1. Class I - Minimal mesangial lupus nephritis, OR 2. Class II - Mesangial proliferative lupus nephritis, in accordance with the International Society of Nephrology (ISN) and the Renal Pathology Society (RPS) 2003 histological classification. With diagnosis made ≥ 6 months prior to study commencement. 16. If inclusion criteria #15 is met, subject must be receiving stable Standard of Care, including hydroxychloroquine, treatment appropriate for class I-II nephritis.
Exclusion criteria
(NONE can apply): 1. Active severe SLE flare with central nervous system (CNS) and/or renal manifestations, pericarditis, active pleuritis, active peritonitis or other SLE manifestations requiring treatment not allowed by the study protocol within 4 weeks of screening 2. Pregnant or breast-feeding 3. Lack of peripheral venous access. 4. History of cardiovascular disease. An acute cardiovascular event within 12 months of study entry, including arterial or venous thrombosis (blood clots). 5. Requirement for a stable dose of corticosteroid \>0.3 mg/kg/day of prednisone or equivalent. 6. Active therapy with human or murine monoclonal antibodies (i.e. belimumab), within 2 months of study entry. 7. Any experimental therapy within 3 months of study entry. 8. Therapy with cyclophosphamide p.o or parenteral; pulse methylprednisolone or IVIG within 4-6 weeks. 9. Subjects being treated with sulfonylureas. 10. Subjects with any the following laboratory abnormalities: serum creatinine \>3.0 mg/dL, WBC \<3,500/μL, ANC \<3,000/μL, absolute lymphocyte count ≤500/μL, Hgb \<8.0 g/dL, platelets \<50,000/μL, ALT and/or AST \>1.5 x upper limit of normal (ULN), alkaline phosphatase \>1.5 ULN. 11. Personal or psychiatric condition that precludes the subject being able to comply with the study requirements or understand and agree to the informed consent process. 12. Recent systemic bacterial, fungal, viral, or parasitic infections. Have required management/treatment or hospitalization for any infection within the last 4 weeks before screening. 13. History of malignancy - except completely excised basal cell carcinoma. 14. Impaired hepatic function 15. Body weight of 260lbs/120kg or more (BMI \> 35) 16. History of tuberculosis (TB) or active, continuing treatment for TB 17. History of or current alcohol or substance abuse Mild SLE only 18. Active lupus nephritis and/or severe renal impairment (estimated or measured GFR \< 50% predicted for age and gender) Moderate SLE only 19. Subjects with recently diagnosed lupus nephritis (diagnosis made \<6 months prior to commencement of study 20. Subjects with active urinary sediment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline Serum Interleukin 6 (IL-6) Levels at the End of Active Dosing, Comparing Treatment to Placebo Cohort. | 4 weeks |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Multiple doses of matched vehicle (no active ingredients) administered intravenously over 60 minutes.
Placebo | 8 |
| Ala-Cpn10 Recombinant minimally modified Chaperonin10 (Cpn10) Multiple doses in the range of 10mg twice weekly to 100mg twice weekly administered intravenously by infusion over 60 minutes.
Ala-Cpn10 | 22 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Ala-Cpn10 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 2 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 6 Participants | 24 Participants |
| Age, Continuous | 43 years STANDARD_DEVIATION 15 | 50 years STANDARD_DEVIATION 18 | 45 years STANDARD_DEVIATION 15 |
| Gender Female | 21 Participants | 7 Participants | 28 Participants |
| Gender Male | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment United States | 22 participants | 8 participants | 30 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 8 | 6 / 22 |
| serious Total, serious adverse events | 0 / 8 | 1 / 22 |
Outcome results
Primary
Change From Baseline Serum Interleukin 6 (IL-6) Levels at the End of Active Dosing, Comparing Treatment to Placebo Cohort.
Time frame: 4 weeks
Population: Analysis Population reflects participants for whom adequate analyzable samples were collected
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline Serum Interleukin 6 (IL-6) Levels at the End of Active Dosing, Comparing Treatment to Placebo Cohort. | 1.6 percentage change from baseline | Standard Deviation 24.7 |
| Ala-Cpn10 - 10mgs in Mild SLE | Change From Baseline Serum Interleukin 6 (IL-6) Levels at the End of Active Dosing, Comparing Treatment to Placebo Cohort. | 987.7 percentage change from baseline | Standard Deviation 2202.1 |
| Ala-Cpn10 - 30mgs in Mild SLE | Change From Baseline Serum Interleukin 6 (IL-6) Levels at the End of Active Dosing, Comparing Treatment to Placebo Cohort. | -82.5 percentage change from baseline | Standard Deviation 20.4 |
| Ala-Cpn10 - 100mgs in Mild SLE | Change From Baseline Serum Interleukin 6 (IL-6) Levels at the End of Active Dosing, Comparing Treatment to Placebo Cohort. | -29.7 percentage change from baseline | Standard Deviation 59.1 |
| Ala-Cpn10 - 30mgs in Moderate SLE | Change From Baseline Serum Interleukin 6 (IL-6) Levels at the End of Active Dosing, Comparing Treatment to Placebo Cohort. | 5000 percentage change from baseline | Standard Deviation 0 |