Vitamin D3 in Pediatric SLE

Inclusion Criteria:

• Written informed consent signed by the subject or parent/guardian as appropriate; child assent as appropriate
• Before the age of 19, met at least 4 of the 11 modified American College of Rheumatology (ACR) 1982 Revised Criteria for the Classification of Systemic Lupus Erythematosus as updated in 1997.
• Date of SLE diagnosis (as described in Inclusion Criterion 2) at least 24 weeks prior to randomization
• Serum 25(OH) D < 20 ng/mL at Screening
• SELENA SLEDAI score > 0 and < 8 at Screening and at Baseline
• If taking prednisone (or equivalent corticosteroid), the dose must be ≤ 15 mg/day or ≤ 0.5 mg/kg/day, whichever is lower, and stable for at least four weeks prior to randomization. Note, if subjects are taking steroids every other day, divide their dose by 2 to evaluate eligibility.
• Stable immunosuppressive dose for at least 12 weeks prior to randomization. Immunosuppressive medications allowed include mycophenolate, azathioprine, methotrexate, antimalarial medications (e.g., hydroxychloroquine), cyclosporine A, tacrolimus, IVIG, and abatacept
• Body weight > 25 kg
• Able to swallow pills at randomization
• Males and females with reproductive potential must agree to practice effective measures of birth control

Exclusion Criteria:

• Any condition or treatment that, in the opinion of the investigator, places the subject at an unacceptable risk as a participant in the trial
• Current pharmacologic vitamin D2 or D3 intake > 800 IU per day or use of calcitriol at any dose over the past four weeks prior to randomization
• Cyclophosphamide or IV glucocorticoid exposure within 12 weeks prior to randomization
• Any BILAG A or B manifestation with the exception of a BILAG B mucocutaneous manifestation at screening, and excluding the renal BILAG criteria (see criterion #5, below)

• Significant renal insufficiency defined as:

  i. Estimated GFR < 60 mL/min/1.73m2 [95] or estimated GFR < 90 mL/min/1.73m2 with a reduction of the GFR by > 15% from the last measurement. ii. Urine dipstick value of 2+ or higher for protein, unless this is a stable value from the last measurement or, urine protein-creatinine ratio ≥ 50 mg/mmol unless the value represents an improvement of ≥ 25% from the last measurement.

• Rituximab or belimumab exposure use within 24 weeks prior to randomization

• The following laboratory parameters at the Screening visit:

  • Platelets < 50,000; WBC < 2,500; ANC < 1,000
  • Hemoglobin < 9 mg/dL
  • ALT, AST, bilirubin > 2x ULN
  • Hypercalcemia (Calcium > ULN)
  • Hypercalciuria (urinary calcium/creatinine ratio > 0.2)
• Primary hyperparathyroidism (known)
• History of nephrolithiasis (known)
• Diabetes mellitus requiring insulin therapy
• Medications that interfere with vitamin D absorption (refer to Section 5.7, Prohibited Medications, for details)
• History of vertebral compression fractures (known)
• Pregnancy (girls ≥ 11 years of age must have a negative urine/serum pregnancy test)
• A history of non-adherence/non-compliance
• Other investigational drug and/or treatment during the four weeks or seven half-lives of the other investigational drug prior to the start of study product dosing (Day 0), whichever is the greater length of time to enrollment
• Current diagnosis of cancer or chronic infection such as Hepatitis B, Hepatitis C, or tuberculosis
• Treatment with digoxin
• Flu vaccination within one week prior to randomization