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

Sponsor:	North Shore Long Island Jewish Health System
Collaborators:	University of Michigan The Cleveland Clinic National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):	North Shore Long Island Jewish Health System
ClinicalTrials.gov Identifier:	NCT00814255

Purpose

This project will test whether adalimumab,and/or galactose 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: Lisinopril, losartan, and atorvastatin Drug: galactose	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Novel Therapies for Resistant FSGS

Resource links provided by NLM:

Drug Information available for: Lisinopril Losartan Losartan potassium Atorvastatin Atorvastatin calcium Adalimumab Galactose

U.S. FDA Resources

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 [ 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:	179
Study Start Date:	December 2008
Estimated Study Completion Date:	October 2013
Estimated Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 2 Conservative medical therapy plus adalimumab	Drug: Adalimumab Adalimumab 24 mg/m2 (maximum dose 40 mg) sc q 14 days
Active Comparator: 1 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
Experimental: conservative medical therapy plus galactose drug: galactose 0.2 g /kg/dose (maximum dose 15g) po BID	Drug: galactose galactose 0.2 g/kg/dose (maximum dose 15 g)po BID

Show Detailed Description

Eligibility

Ages Eligible for Study:	1 Year to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Primary FSGS confirmed by renal biopsy OR documentation of a genetic mutation in a podocyte protein associated with the disease
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 1-65 years at onset of proteinuria
Age 1-65 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	646-501-2663	howard.trachtman@nyumc.org
Contact: Debbie Gipson, MD	734-936-4210	dgipson@med.umich.edu

Locations

United States, Florida
Miami Children's Hospital	Recruiting
Miami, Florida, United States, 33155
Contact: Ana Paredes, MD 305-699-7116 ana.paredes@mch.edu
Principal Investigator: Ana Paredes, MD
United States, Georgia
Emory University	Recruiting
Atlanta, Georgia, United States, 30322
Contact: Lawrence Greenbaum, MD 404-727-5750 LGREEN6@emory.edu
Principal Investigator: Lawrence Greenbaum, MD
United States, Kansas
University of Kansas	Recruiting
Kansas City, Kansas, United States, 66160
Contact: Ellen McCarthy, MD 913-588-0709 emccarthy@kumc.edu
Principal Investigator: Ellen McCarthy, MD
United States, Massachusetts
Boston Children's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Michael Somers, MD 617-355-6129 michael.somers@childrens.harvard.edu
Principal Investigator: Michael Somers, MD
United States, Michigan
University of Michigan	Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Debbie Gipson, MD 734-936-4210 dgipson@med.umich.edu
Principal Investigator: Debbie Gipson, MD
United States, Minnesota
Mayo Clinic	Recruiting
Rochester, Minnesota, United States, 55901
Contact: Fernando Fervenza, MD, PhD 507-266-7083 fervenza.fernando@mayo.edu
Contact: Shirley Jennison 507-255-0231 jennison.shirley@mayo.edu
Sub-Investigator: Stephen Erickson, MD
Sub-Investigator: Marie Hogan, MD
Sub-Investigator: Nelson Leung, MD
Sub-Investigator: Carl Cramer, MD
United States, Missouri
Children's Mercy Hospital	Recruiting
Kansas City, Missouri, United States, 64108
Contact: Tarak Srivastava, MD 816-234-3010 tsrivastava@cmh.edu
Principal Investigator: Tarak Srivastava, MD
Cardinal Glennon Children's Medical Center	Recruiting
Saint Louis, Missouri, United States, 63104
Contact: Ellen Wood, MD 314-577-5662
Principal Investigator: Ellen Wood, MD
United States, New York
Steven and Alexandra Cohen Children's Medical Center of New York	Recruiting
New Hyde Park, New York, United States, 11040
Contact: Christine Sethna, MD 718-470-3423 csethna@nshs.edu
Contact: Rachel Frank, RN 718-470-3493 rfrank@nshs.edu
Principal Investigator: Christine Sethna, MD
Columbia University Medical Center	Recruiting
New York, New York, United States, 10032
Contact: Andrew Bomback, MD asb68@columbia.edu
Contact: Melanie Foley 212-305-5038 mf2162@columbia.edu
Principal Investigator: Andrew Bomback, MD
United States, North Carolina
Carolinas Medical Center	Recruiting
Charlotte, North Carolina, United States, 28207
Contact: Susan Massengill, MD 704-381-8809 susan.massengill@carolinashealthcare.org
Contact: Jennifer LaMothe, RN, BSN, CCRC, CPN 704-347-4052
Principal Investigator: Susan Massengill, MD
United States, Ohio
Cincinnati Children's Hospital Medical Center	Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Jens Goebel, MD 513-636-4531
Contact: Barbara Logan 513-636-9834
Principal Investigator: Jens Goebel, MD
Ohio State University	Recruiting
Columbus, Ohio, United States, 43205
Contact: John Mahan, MD 614-722-4360 MahanJ@pediatrics.ohio-state.edu
Principal Investigator: John Mahan, MD
United States, Oregon
Doernbecher Children's Hospital	Recruiting
Portland, Oregon, United States, 97239
Contact: Amira Al-Uzri, MD 503-494-7327 aluzri@ohsu.edu
Principal Investigator: Amira Al-Uzri, MD
United States, South Carolina
Medical University of South Carolina	Recruiting
Charleston, South Carolina, United States, 29425
Contact: Milos Budisavljevics, MD 843-792-4123 budisamn@musc.edu
Principal Investigator: Milos Budisavljevics, MD
United States, Texas
Texas Tech University	Recruiting
El Paso, Texas, United States, 79905
Contact: German Hernandez, MD 915-545-6626 german.hernandez@ttuhsc.edu
Principal Investigator: German Hernandez, MD
Canada, Alberta
University of Alberta	Recruiting
Edmonton, Alberta, Canada, T6G 2R7
Contact: Maury Pinsk, MD 780-248-5560
Principal Investigator: Maury Pinsk, MD

Sponsors and Collaborators

North Shore Long Island Jewish Health System

University of Michigan

The Cleveland Clinic

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

Investigators

Principal Investigator:	Howard Trachtman, MD	Steven and Alexandra Cohen Children's Medical Center of New York
Principal Investigator:	Debbie Gipson, MD	University of Michigan
Principal Investigator:	Jennifer Gassman, PhD	The Cleveland Clinic

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Publications:

Joy MS, Gipson DS, Dike M, Powell L, Thompson A, Vento S, Eddy A, Fogo AB, Kopp JB, Cattran D, Trachtman H. Phase I trial of rosiglitazone in FSGS: I. Report of the FONT Study Group. Clin J Am Soc Nephrol. 2009 Jan;4(1):39-47. Epub 2008 Dec 10.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Trachtman H, Vento S, Gipson D, Wickman L, Gassman J, Joy M, Savin V, Somers M, Pinsk M, Greene T. Novel therapies for resistant focal segmental glomerulosclerosis (FONT) phase II clinical trial: study design. BMC Nephrol. 2011 Feb 10;12(1):8.

Joy MS, Gipson DS, Powell L, MacHardy J, Jennette JC, Vento S, Pan C, Savin V, Eddy A, Fogo AB, Kopp JB, Cattran D, Trachtman H. Phase 1 trial of adalimumab in Focal Segmental Glomerulosclerosis (FSGS): II. Report of the FONT (Novel Therapies for Resistant FSGS) study group. Am J Kidney Dis. 2010 Jan;55(1):50-60. Epub 2009 Nov 22.

Responsible Party:	North Shore Long Island Jewish Health System
ClinicalTrials.gov Identifier:	NCT00814255 History of Changes
Other Study ID Numbers:	DK70341FII, R33DK070341
Study First Received:	December 22, 2008
Last Updated:	December 30, 2011
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
GALACTOSE

Additional relevant MeSH terms:

Glomerulosclerosis, Focal Segmental
Glomerulonephritis
Nephritis
Kidney Diseases
Urologic Diseases
Lisinopril
Losartan
Atorvastatin
Adalimumab
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents

Cardiovascular Agents
Therapeutic Uses
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents
Anti-Arrhythmia Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Antirheumatic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on February 09, 2012