Novel Therapies for Resistant FSGS (FONT II): Phase II Clinical Trial - Full Text View

Sponsors and Collaborators:	North Shore Long Island Jewish Health System University of North Carolina The Cleveland Clinic
Information provided by:	North Shore Long Island Jewish Health System
ClinicalTrials.gov Identifier:	NCT00814255

Purpose

This project will test whether rosiglitazone and/or adalimumab can safely reduce proteinuria (abnormal amounts of protein in the urine) and protect kidney function better than standard treatment for patients with focal segmental glomerulosclerosis (FSGS).

Condition	Intervention	Phase
Focal Segmental Glomerulosclerosis	Drug: Adalimumab Drug: Rosiglitazone Drug: Lisinopril, losartan, and atorvastatin	Phase II

Drug Information available for: Adalimumab Lisinopril Atorvastatin Atorvastatin calcium Rosiglitazone Rosiglitazone Maleate Corticosteroids Losartan Losartan potassium

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	Novel Therapies for Resistant FSGS

Further study details as provided by North Shore Long Island Jewish Health System:

Primary Outcome Measures:

A reduction in proteinuria at 6 months by > 50% of the value at the time of screening, and/or [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
An estimated GFR (GFRe) that is stable compared to value at enrollment [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Adverse effect profile [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Patient satisfaction score using the TSQM questionnaire (76) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Percent change in proteinuria (evaluated as a continuous variable) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
Change in or time to doubling of GFRe [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	126
Study Start Date:	December 2008
Estimated Study Completion Date:	April 2011
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
2: Experimental Conservative medical therapy plus adalimumab	Drug: Adalimumab Adalimumab 24 mg/m2 (maximum dose 40 mg) sc q 14 days
3: Experimental Conservative medical therapy plus rosiglitazone	Drug: Rosiglitazone 4 mg/m2/day divided BID
1: Active Comparator Conservative medical therapy (lisinopril, losartan, atorvastatin)	Drug: Lisinopril, losartan, and atorvastatin Lisinopril PO 10-20 mg per day Losartan PO 25-50 mg per day Atorvastatin PO 10-20 mg per day

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Eligibility

Ages Eligible for Study:	1 Year to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Primary FSGS confirmed by renal biopsy
Failure to respond to prior therapy at least one of the following immunosuppressive medications -- cyclosporine, tacrolimus, mycophenolate mofetil, sirolimus - or other agents prescribed to lower proteinuria
Age 1-50 years at onset of proteinuria
Age 1-51 years at time of randomization
Estimated GFR ≥40 mL/min/1.73 m2 using Schwartz (age <18 yr) or Cockroft-Gault (age <18 yr) formula at screening and ≥30 mL/min/1.73 m2 at the end of the Run-In Period and at the time of randomization
Up/c > 1.0 g/g creatinine on first morning void
Steroid resistance defined as failure to achieve sustained Up/c < 1.0 following a standard course of prednisone/prednisolone/methylprednisolone prescribed for FSGS therapy, OR contraindication/anticipated intolerance to steroid therapy defined as severe obesity, documented decreased bone density, family history of diabetes, or a psychiatric disorder.
Willingness to follow the protocol, including medications, baseline and follow-up visits, and procedures.

Exclusion Criteria:

Lactation, pregnancy, or refusal of birth control in women of child bearing potential
Participation in another therapeutic trial involving protocol mandated administration of a immunosuppressive medication concurrently or 30 days prior to randomization
Active/serious infection (including, but not limited to Hepatitis B or C, HIV)
History of malignancy
Abnormality in age appropriate cancer screening in accord with ACS 2003 guidelines (appendix 17.6)
Patients with uncontrolled blood pressure > 140/90 or > 95th percentile for age/height at the end of the run in period
Diabetes mellitus Type I or II
Organ transplantation
Congestive heart failure
History of prior myocardial infarction
SLE or multiple sclerosis
Hepatic disease, defined as serum ALT/AST levels more than 2.5x the upper limit of normal
Hematocrit <27%
Immunosuppressive therapy with cyclosporine, tacrolimus, mycophenolate mofetil, azathioprine, or rapamycin in the 30 days prior or Rituximab in the 90 days prior to randomization
Prior treatment with the study medications, rosiglitazone or adalimumab
Allergy to one of the study medications, i.e., rosiglitazone, adalimumab, lisinopril, losartan or atorvastatin

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00814255

Contacts

Contact: Howard Trachtman, MD	718-470-3423	trachtma@lij.edu
Contact: Debbie Gipson, MD	919-966-2561 ext 235	debbie_gipson@unc.med.edu

Locations

United States, Florida
University of Miami	Recruiting
Miami, Florida, United States
Contact: Ana Paredes, MD ana.paredes@mch.edu
Principal Investigator: Ana Paredes, MD
United States, Massachusetts
Boston Children's Hospital	Recruiting
Boston, Massachusetts, United States, USA
Contact: Michael Somers, MD 617-355-6129 michael.somers@childrens.harvard.edu
Principal Investigator: Michael Somers, MD
United States, New York
Schneider Children's Hospital	Recruiting
New Hyde Park, New York, United States, 11040
Principal Investigator: Howard Trachtman, MD
United States, North Carolina
University of North Carolina	Recruiting
Chapel Hill, North Carolina, United States, 27599-7155
Contact: Debbie Gipson, MD 919-966-2561 ext 235 debbie_gipson@unc.med.edu
Principal Investigator: Debbie Gipson, MD

Sponsors and Collaborators

North Shore Long Island Jewish Health System

University of North Carolina

The Cleveland Clinic

Investigators

Principal Investigator:	Howard Trachtman, MD	Schneider Children's Hospital of NS-LIJ Health System
Principal Investigator:	Debbie Gipson, MD	University of North Carolina
Principal Investigator:	Jennifer Gassman, PhD	The Cleveland Clinic

More Information

Access to the FSGS-Clinical Trial and the FONT Trials This link exits the ClinicalTrials.gov site

Responsible Party:	Schneider Children's Hospital of NS-LIJ Health System ( Howard Trachtman MD )
Study ID Numbers:	DK70341FII, R33DK70341
Study First Received:	December 22, 2008
Last Updated:	December 23, 2008
ClinicalTrials.gov Identifier:	NCT00814255
Health Authority:	United States: Food and Drug Administration; United States: Federal Government

Keywords provided by North Shore Long Island Jewish Health System:

Primary FSGS
Steroid Resistant
Rosiglitazone
Adalimumab
Resistant primary FSGS defined as failure to achieve remission in response to corticosteroids and one other immunosuppressive medication

Study placed in the following topic categories:

Glomerulosclerosis, Focal Segmental
Losartan
Glomerulonephritis
Urologic Diseases
Nephritis
Lisinopril

Kidney Diseases
Angiotensin II
Adalimumab
Rosiglitazone
Atorvastatin
Focal segmental glomerulosclerosis

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Cardiotonic Agents
Antilipemic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Cardiovascular Agents
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors

Antihypertensive Agents
Protective Agents
Pharmacologic Actions
Protease Inhibitors
Angiotensin II Type 1 Receptor Blockers
Hypoglycemic Agents
Therapeutic Uses
Angiotensin-Converting Enzyme Inhibitors
Anti-Arrhythmia Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on January 15, 2009