Clinical trial NCT01838694: Double-Blinded, Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Biochemical Activity of Intravenous Cpn10 Administration in Subjects With Mild to Moderate SLE.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lupus Erythematosus, Systemic
Lead sponsor: Invion, Inc.
Sponsor class: INDUSTRY
First posted: 2013-04-24
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline Serum Interleukin 6 (IL-6) Levels at the End of Active Dosing, Comparing Treatment to Placebo Cohort.
timeFrame: 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: Abel Buchheim Pharmaceutical Research
state: Florida
city: Chicago
country: United States
facility: Northwestern University School of Medicine
state: Illinois
city: Altoona
country: United States
facility: Altoona Arthritis and Osteoporosis Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: Metroplex Clinical Research Center
state: Texas
Study officials:
References: