title: Efficacy of galactose and adalimumab in patients with resistant focal segmental glomerulosclerosis: report of the font clinical trial group.
abstract: BACKGROUND
  Patients with resistant focal segmental glomerulosclerosis (FSGS) who are unresponsive to corticosteroids and other immunosuppressive agents are at very high risk of progression to end stage kidney disease. In the absence of curative treatment, current therapy centers on renoprotective interventions that reduce proteinuria and fibrosis. The FONT (Novel Therapies for Resistant FSGS) Phase II clinical trial (NCT00814255, Registration date December 22, 2008) was designed to assess the efficacy of adalimumab and galactose compared to standard medical therapy which was comprised of lisinopril, losartan, and atorvastatin.
  
  
  METHODS
  Key eligibility criteria were biopsy confirmed primary FSGS or documentation of a causative genetic mutation, urine protein:creatinine ratio >1.0 g/g, and estimated glomerular filtration rate (eGFR) >40 ml/min/1.73 m(2). The experimental treatments - adalimumab, galactose, standard medical therapy-- were administered for 26 weeks. The primary endpoint was a 50 % reduction in proteinuria with stable eGFR.
  
  
  RESULTS
  Thirty-two subjects were screened and 21 were assigned to one of the three study arms. While none of the adalimumab-treated subjects achieved the primary outcome, 2 subjects in the galactose and 2 in the standard medical therapy arm had a 50 % reduction in proteinuria without a decline in eGFR. The proteinuria response did not correlate with serial changes in the serum glomerular permeability activity measured by the Palb assay or soluble urokinase plasminogen activator receptor (suPAR). There were no serious adverse effects related to treatments in the study.
  
  
  CONCLUSIONS
  Recruitment into this trial that addressed patients with resistant FSGS fell short of the enrollment goal. Our findings suggest that future studies of novel therapies for rare glomerular diseases such as FSGS may benefit from enrollment of patients earlier in the course of their disease. In addition, better identification of patients who are likely to respond to a new treatment based on biomarkers suggesting involvement of the disease pathway targeted by the experimental agent may reduce the required sample size and increase the likelihood of a favorable outcome.
authors.affiliation: NYU Langone Medical Center, CTSI, Room #110, 227 E 30th Street, New York, NY, USA. howard.trachtman@nyumc.org.
authors.forename: Howard
authors.initials: H
authors.lastname: Trachtman
authors.affiliation: NYU Langone Medical Center, CTSI, Room #110, 227 E 30th Street, New York, NY, USA. Suzanne.vento@nyumc.org.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Vento
authors.affiliation: University of Michigan, Ann Arbor, MI, USA. egalopin@med.umich.edu.
authors.forename: Emily
authors.initials: E
authors.lastname: Herreshoff
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH, USA. mradeva@bio.ri.ccf.org.
authors.forename: Milena
authors.initials: M
authors.lastname: Radeva
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH, USA. gassmaj@ccf.org.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gassman
authors.affiliation: Albert Einstein College of Medicine, Bronx, NY, USA. Daniel.Stein@einstein.yu.edu.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Stein
authors.affiliation: Kansas City Veteran's Administration Medical Center, Kansas City, MO, USA. vjsavin@gmail.com.
authors.forename: Virginia J
authors.initials: VJ
authors.lastname: Savin
authors.affiliation: Kansas City Veteran's Administration Medical Center, Kansas City, MO, USA. mukut.sharma@va.gov.
authors.forename: Mukut
authors.initials: M
authors.lastname: Sharma
authors.affiliation: Rush University Medical Center, Chicago, IL, USA. jochen_reiser@rush.edu.
authors.forename: Jochen
authors.initials: J
authors.lastname: Reiser
authors.affiliation: Rush University Medical Center, Chicago, IL, USA. Changli_Wei@rush.edu.
authors.forename: Changli
authors.initials: C
authors.lastname: Wei
authors.affiliation: Boston Children's Medical Center, Boston, MA, USA. michael.somers@childrens.harvard.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Somers
authors.affiliation: Children's Mercy Hospital, Kansas City, MO, USA. tsrivastava@cmh.edu.
authors.forename: Tarak
authors.initials: T
authors.lastname: Srivastava
authors.affiliation: University of Michigan, Ann Arbor, MI, USA. dgipson@med.umich.edu.
authors.forename: Debbie S
authors.initials: DS
authors.lastname: Gipson
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use*; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D005690:Galactose / Q000097:blood / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D011507:Proteinuria / Q000188:drug therapy / Q000209:etiology; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D055293:Receptors, Urokinase Plasminogen Activator; D000068879:Adalimumab; D005690:Galactose