| Methods |
Treatment, randomized, open label, active control, parallel assignment, safety study
To assess the safety and tolerability of two novel drugs ‐ a TNF‐α antagonist and a PPARϒ agonist ‐ in patients with resistant FSGS. To conduct a pharmacokinetic (PK) assessment of the selected agents to enable selection of medication regimens for investigation in a randomized Phase II study.
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| Participants |
Age: 2 to 40 years
Gender: Both
Inclusion criteria:
Aged 2‐42 years at onset of proteinuria Aged ≤ 42 years at time of randomization (randomization date before 43rd birthday) -
Estimated glomerular filtration rate (GFR) ≥ 40 mL/min/1.73 m² at most recent measurement prior to randomization
For patients < age 18 years: Schwartz formula For patients ≥ age 18 years: Cockroft‐Gault formula
Up/c > 1.0 g/g creatinine on first morning void at time of randomization Biopsy confirmed as primary FSGS (including all subtypes) by study pathologist. Steroid resistance: During the last treatment course with high dose steroids prior to randomization, the patient must have demonstrated steroid resistance defined below and not have had a complete remission of proteinuria (Up/c < 0.2 or dipstick urine protein negative/trace) subsequently. The course of steroid treatment that defines resistance must be the same or equivalent to at least 4 weeks of every day dosing with a minimum cumulative dose of 56 mg/kg or 1680 mg of prednisone or its equivalent. May be taking angiotensin‐converting enzyme inhibitor (ACEI), angiotensin receptor blocking agent (ARB), vitamin E, or lipid lowering therapy Willingness to comply with clinical trial protocol, medications, and follow‐up visits, etc. Screen failure in FSGS‐CT based on prior treatment with excluded medication Treatment failure in FSGS‐CT based on failure to achieve remission after 26 weeks or 52 weeks of test therapy, i.e., cyclosporine or mycophenolate mofetil (MMF) + oral dexamethasone pulses
Exclusion Criteria
Secondary FSGS Treated with cyclophosphamide, chlorambucil, levamisole, methotrexate, nitrogen mustard, or other immunosuppressive medications in the 30 days prior to randomization Lactation, pregnancy, or refusal of birth control in women of child bearing potential Participation in another therapeutic trial concurrently or for 30 days prior to randomization Active/serious infection (including, but not limited to hepatitis B or C, HIV) Malignancy Systemic lupus erythematosus (SLE) or multiple sclerosis Hepatic disease defined as serum AST/ALT > 2.5X the upper limit of normal Patients with blood pressure > 140/95 or > 95th percentile for age/height while receiving maximal doses of 3 or more antihypertensive agents. Diabetes mellitus (DM) type I or II. Hematocrit < 30% Organ transplantation -
Obesity (based on estimated dry weight at disease onset prior to steroid therapy) defined as:
Body mass index (BMI) > 97th percentile for age if aged 2‐20 years BMI > 40 kg/m2 if aged ≥ 21 years
Allergy to study medications Inability to consent/assent
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