Focal Segmental Glomerulosclerosis Clinical Trial (FSGS-CT)

NCT00135811 | Completed Phase 3 DMC

• 1 other identifier: 63490 (completed)
• Study Type: interventional
• Target: 207
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Glomerulosclerosis, Focal

Keywords

Focal Segmental Glomerulosclerosis

Outcome Measures

Primary Outcomes (1)

• The primary outcome is a 6-level ordinal variable defined based on the achievement of remission from proteinuria during the first 52 weeks after randomization.

  first 52 weeks after randomization.

Secondary Outcomes (1)

• The main secondary outcome is a 5-level ordinal variable defined based on the persistence of remissions after immunosuppressive agents are withdrawn.

  based on the participant's level of proteinuria during the period from week 52 through week 78 following withdrawal of CSA or MMF/Pulse steroids

Study Arms (2)

1

ACTIVE COMPARATOR

Cyclosporin

Drug: Cyclosporin

2

ACTIVE COMPARATOR

MMF and Dexamethasone

Drug: MMF and Dexamethasone

Interventions

Cyclosporin DRUG

Participants assigned to this group will initiate treatment with CSA, 5-6 mg/kg per day with a 250 mg/day maximum starting dose, divided into two daily doses. The CSA dose will be adjusted based on drug levels determined at specified study visits in order to achieve a 12-hour trough concentration in the therapeutic range of 100-250 ng/ml.

1

MMF and Dexamethasone DRUG

MMF, 25-36 mg/kg per day with a maximum dose of 2 g/day divided into two daily doses. The dose range reflects the use of fixed size (250 mg) capsules and application of defined daily doses to specific weight ranges (see Table below). In younger children or those participants who are unable to swallow capsules, a liquid formulation will be used to provide 36 mg/kg per day to a maximum of 2 g per day. The starting MMF dose will be 0.5-0.67 of the full dose for 2 weeks before advancing to the full dose for the duration of the 12-month treatment period. Dexamethasone, 0.9 mg/kg per dose, with a maximum dose of 40 mg

2

Eligibility Criteria

• Age: 2 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• The Cleveland Clinic: collaborator

Study Sites (1)

Data Coordinating Center; Cleveland Clinic Foundation; Quantitative Health Sciences; 9500 Euclid Avenue

Cleveland, Ohio, 44195-5196, United States

Location

Related Publications (5)

• Liu ID, Willis NS, Craig JC, Hodson EM. Interventions for idiopathic steroid-resistant nephrotic syndrome in children. Cochrane Database Syst Rev. 2025 May 8;5(5):CD003594. doi: 10.1002/14651858.CD003594.pub7.

  PMID: 40337980 DERIVED

• Hodson EM, Sinha A, Cooper TE. Interventions for focal segmental glomerulosclerosis in adults. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD003233. doi: 10.1002/14651858.CD003233.pub3.

  PMID: 35224732 DERIVED

• Li Q, Gulati A, Lemaire M, Nottoli T, Bale A, Tufro A. Rho-GTPase Activating Protein myosin MYO9A identified as a novel candidate gene for monogenic focal segmental glomerulosclerosis. Kidney Int. 2021 May;99(5):1102-1117. doi: 10.1016/j.kint.2020.12.022. Epub 2021 Jan 4.

  PMID: 33412162 DERIVED

• Gipson DS, Trachtman H, Kaskel FJ, Greene TH, Radeva MK, Gassman JJ, Moxey-Mims MM, Hogg RJ, Watkins SL, Fine RN, Hogan SL, Middleton JP, Vehaskari VM, Flynn PA, Powell LM, Vento SM, McMahan JL, Siegel N, D'Agati VD, Friedman AL. Clinical trial of focal segmental glomerulosclerosis in children and young adults. Kidney Int. 2011 Oct;80(8):868-78. doi: 10.1038/ki.2011.195. Epub 2011 Jul 6.

  PMID: 21734640 DERIVED

• Gipson DS, Trachtman H, Kaskel FJ, Radeva MK, Gassman J, Greene TH, Moxey-Mims MM, Hogg RJ, Watkins SL, Fine RN, Middleton JP, Vehaskari VM, Hogan SL, Vento S, Flynn PA, Powell LM, McMahan JL, Siegel N, Friedman AL. Clinical trials treating focal segmental glomerulosclerosis should measure patient quality of life. Kidney Int. 2011 Mar;79(6):678-685. doi: 10.1038/ki.2010.485. Epub 2010 Dec 22.

  PMID: 21178977 DERIVED

MeSH Terms

Conditions

Glomerulosclerosis, Focal Segmental

Interventions

Cyclosporine; Dexamethasone

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated

Study Officials

• Aaron Friedman, MD

  University of Minnesota

  STUDY CHAIR

• Marva Moxey-Mims, MD, FAAP

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: August 24, 2005
• First Posted: August 26, 2005
• Study Start: November 1, 2004
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: May 22, 2012

Record last verified: 2012-05

Locations

US (1)