Focal Segmental Glomerulosclerosis Clinical Trial (FSGS-CT)

• Status: Completed
• Trial end date: 2009-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The FSGS Clinical Trial is a multi-center, prospective, controlled, open label randomized trial designed to determine if treatment with mycophenolate mofetil (MMF) in conjunction with pulse steroids is superior to treatment with Cyclosporine-A (CSA) in inducing remission from proteinuria over 12 months.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborator: The Cleveland Clinic
• Treatments: BB 1101; Cyclosporine; Cyclosporins; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate

Criteria

Inclusion Criteria:

• Age 2-40 years at onset of signs or symptoms of FSGS

• Age ≤ 40 years at time of randomization (randomization date before 41st birthday)

• Estimated GFR ≥ 40 ml/min/1.73 m2 at most recent measure prior to randomization

• For participants < age 18 years: Schwartz formula

• For participants ≥ age 18 years: Cockroft-Gault formula

• Up/c > 1.0 g protein/g creatinine on first am void at time of randomization

• Biopsy confirmed as primary FSGS (including all subtypes) by study pathologist. A minimum of 1 glomerulus demonstrating segmental sclerosis on light microscopy will be required to confirm the diagnosis.

• Steroid resistance: The participant must have demonstrated steroid resistance (defined as a failure to achieve a sustained Up/c ≤ 1.0) based on at least one treatment course with high dose steroids prior to randomization which satisfies both of the following conditions:

• minimal treatment duration of 4 weeks

• minimum cumulative dose of 56 mg/kg or 1680 mg of prednisone or its equivalent. In addition, the participant must not have had a complete remission of proteinuria (Up/c < 0.2 or dipstick urine protein 0/trace) subsequent to the latest qualifying 4-week course demonstrating steroid resistance.

• Willingness to follow the clinical trial protocol, including medications, and baseline and follow-up visits and procedures.

• Participants may be taking ACEI, ARB, Vitamin E, or lipid lowering therapy.

Exclusion Criteria:

• Secondary FSGS

• Prior therapy with sirolimus, CSA, tacrolimus, MMF, or azathioprin (Imuran)

• Treated with cytoxan, chlorambucil, levamisole, methotrexate, or nitrogen mustard in the last 30 days

• Lactation, pregnancy, or refusal of birth control in women of child bearing potential

• Participation in another therapeutic trial concurrently or 30 days prior to randomization

• Active/serious infection (including, but not limited to Hepatitis B, C, or HIV)

• Malignancy

• Blood pressure > 140/95 or > 95th percentile for age/height.

• Participant is receiving 4 or more antihypertensive agents for the primary purpose of controlling blood pressure.

• Participants with previously diagnosed diabetes mellitus type I or II: the diagnosis of DM I or II will be based on local criteria for participants with an established diagnosis. If hyperglycemia is detected during the screening period, the WHO criteria for the diagnosis of DM I and II will be used.

• Clinical evidence of cirrhosis or chronic active liver disease

• Abnormal laboratory values at the time of study entry:

• Absolute neutrophil count (ANC) < 2000/mm3, or

• Hematocrit (HCT) < 28%

• History of significant gastrointestinal disorder, e.g, severe chronic diarrhea (> 5 watery stools per day) or active peptic ulcer disease.

• Organ transplantation

• Obesity (based on estimated dry weight at onset of disease prior to steroid therapy) defined as

• BMI > 97th percentile for age if aged 2-20 years

• BMI > 40 kg/m2 for age ≥21 years

• Allergy to study medications

• Inability to consent/assent

Note: Participants with conditions meeting exclusion criteria at a particular evaluation for eligibility may be re-evaluated at a later time to determine if the conditions have changed so that all entry criteria are met. In particular, if blood pressure > 140/95 or > 95th percentile for age/height while the participant is on less than three antihypertensive agents, the participant may be re-evaluated for eligibility after adding other antihypertensive agents so long as the total number of agents does not exceed three.