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

NCT00814255 | Completed Phase 2 Results DMC

• 2 other identifiers: DK70341FIIR33DK070341
• Study Type: interventional
• Target: 32
• Locations: 2 countries
• Sites: 18

Brief Summary

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).

Conditions

Focal Segmental Glomerulosclerosis

Keywords

Primary FSGS; Steroid Resistant; Rosiglitazone; Adalimumab; Resistant primary FSGS; GALACTOSE

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Reduction in Proteinuria at 6 Months by > 50% of the Value at Screening AND Stable GFR Defined as Greater Than 75 ml/Min/1.73m2 in Those With an Initial Value Above 90 OR Within 25% of Baseline for Remaining Patients

  Number of participants with a reduction in proteinuria at 6 months by \> 50% of the value at screening AND stable GFR defined as greater than 75 ml/min/1.73m2 in those with an initial value above 90 OR within 25% of baseline for remaining patients.

  baseline and 6 months

Secondary Outcomes (4)

• Patient Satisfaction Score Using the Treatment Satisfaction Questionnaire for Medication (TSQM Questionnaire)

  Baseline and 6 months

• Number of Participants With Adverse Events

  Up to 7 months

• Percent Change in Proteinuria

  Baseline and 6 months

• Percent Change in or Time to Doubling of Serum Creatinine

  Baseline and 6 months

Study Arms (3)

2

EXPERIMENTAL

Conservative medical therapy plus adalimumab

Drug: Adalimumab

1

ACTIVE COMPARATOR

Conservative medical therapy (lisinopril, losartan, atorvastatin)

Drug: Lisinopril, losartan, and atorvastatin

conservative medical therapy plus galactose

EXPERIMENTAL

drug: galactose 0.2 g /kg/dose (maximum dose 15g) po BID

Drug: galactose

Interventions

Adalimumab DRUG

Adalimumab 24 mg/m\^2 (maximum dose 40 mg) sc q 14 days

2

Lisinopril, losartan, and atorvastatin DRUG

Lisinopril PO 10-20 mg per day Losartan PO 25-50 mg per day Atorvastatin PO 10-20 mg per day

1

galactose DRUG

galactose 0.2 g/kg/dose (maximum dose 15 g)po BID

conservative medical therapy plus galactose

Eligibility Criteria

• Age: 1 Year - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• NYU Langone Health: lead
• University of Michigan: collaborator
• The Cleveland Clinic: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (18)

University of Miami

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Kansas

Kansas City, Kansas, 66160, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55901, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

Location

Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, 11040, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Carolinas Medical Center

Charlotte, North Carolina, 28207, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Ohio State University

Columbus, Ohio, 43205, United States

Location

Doernbecher Children's Hospital

Portland, Oregon, 97239, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Texas Tech University

El Paso, Texas, 79905, United States

Location

University of Alberta

Edmonton, Alberta, T6G 2R7, Canada

Location

Related Publications (6)

• 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. doi: 10.2215/CJN.02310508. Epub 2008 Dec 10.

  PMID: 19073787 RESULT

• Trachtman H, Vento S, Herreshoff E, Radeva M, Gassman J, Stein DT, Savin VJ, Sharma M, Reiser J, Wei C, Somers M, Srivastava T, Gipson DS. Efficacy of galactose and adalimumab in patients with resistant focal segmental glomerulosclerosis: report of the font clinical trial group. BMC Nephrol. 2015 Jul 22;16:111. doi: 10.1186/s12882-015-0094-5.

  PMID: 26198842 RESULT

• 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

• 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;12:8. doi: 10.1186/1471-2369-12-8.

  PMID: 21310077 DERIVED

• 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. doi: 10.1053/j.ajkd.2009.08.019. Epub 2009 Nov 22.

  PMID: 19932542 DERIVED

MeSH Terms

Conditions

Glomerulosclerosis, Focal Segmental

Interventions

Adalimumab; Lisinopril; Losartan; Atorvastatin; Galactose

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dipeptides; Oligopeptides; Peptides; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Pyrroles; Heptanoic Acids; Fatty Acids; Lipids; Hexoses; Monosaccharides; Sugars; Carbohydrates

Limitations and Caveats

1. Limited sample size 2. Extended enrollment period 3. Replacement of rosiglitazone with galactose after start of trial

Results Point of Contact

• Title: Howard Trachtman
• Organization: NYUmed

howard.trachtman@nyumc.org

646-501-2663

Study Officials

• Howard Trachtman, MD

  NYU Langone Medical Center

  PRINCIPAL INVESTIGATOR

• Debbie Gipson, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Jennifer Gassman, PhD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2008
• First Posted: December 24, 2008
• Study Start: December 1, 2008
• Primary Completion: June 1, 2013
• Study Completion: February 1, 2014
• Last Updated: July 11, 2016
• Results First Posted: July 11, 2016

Record last verified: 2016-07

Data Sharing

• IPD Sharing: Will share

Locations

US (17); CA (1)