Novel Therapies for Resistant FSGS (FONT II): Phase II Clinical Trial

This study has been completed.
Sponsor:
Collaborators:
University of Michigan
The Cleveland Clinic
Information provided by (Responsible Party):
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT00814255
First received: December 22, 2008
Last updated: April 10, 2014
Last verified: April 2014
  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 2

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:


Further study details as provided by New York University School of Medicine:

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 ]

Enrollment: 23
Study Start Date: December 2008
Study Completion Date: February 2014
Primary Completion Date: June 2013 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Kansas
University of Kansas
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55901
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Cardinal Glennon Children's Medical Center
Saint Louis, Missouri, United States, 63104
United States, New York
Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, United States, 11040
Columbia University Medical Center
New York, New York, United States, 10032
NYU Langone Medical Center
New York, New York, United States, 10016
United States, North Carolina
Carolinas Medical Center
Charlotte, North Carolina, United States, 28207
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Ohio State University
Columbus, Ohio, United States, 43205
United States, Oregon
Doernbecher Children's Hospital
Portland, Oregon, United States, 97239
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
Texas Tech University
El Paso, Texas, United States, 79905
Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada, T6G 2R7
Sponsors and Collaborators
New York University School of Medicine
University of Michigan
The Cleveland Clinic
Investigators
Principal Investigator: Howard Trachtman, MD NYU Langone Medical Center
Principal Investigator: Debbie Gipson, MD University of Michigan
Principal Investigator: Jennifer Gassman, PhD The Cleveland Clinic
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: New York University School of Medicine
ClinicalTrials.gov Identifier: NCT00814255     History of Changes
Other Study ID Numbers: DK70341FII, R33DK070341
Study First Received: December 22, 2008
Last Updated: April 10, 2014
Health Authority: United States: Food and Drug Administration
United States: Federal Government

Keywords provided by New York University School of Medicine:
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
Kidney Diseases
Nephritis
Urologic Diseases
Adalimumab
Atorvastatin
Lisinopril
Losartan
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Anti-Arrhythmia Agents
Anti-Inflammatory Agents
Anticholesteremic Agents
Antihypertensive Agents
Antimetabolites
Antirheumatic Agents
Cardiotonic Agents
Cardiovascular Agents
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014