title: Novel therapies for resistant focal segmental glomerulosclerosis (FONT) phase II clinical trial: study design.
abstract: BACKGROUND
  The lack of adequate randomized clinical trials (RCT) has hindered identification of new therapies that are safe and effective for patients with primary focal segmental glomerulosclerosis (FSGS), especially in patients who fail to respond to corticosteroids and immunosuppressive therapies. Recent basic science advances have led to development of alternative treatments that specifically target aberrant pathways of fibrosis which are relevant to disease progression in FSGS. There is a need for a flexible Phase II study design which will test such novel antifibrotic strategies in order to identify agents suitable for phase III testing.
  
  
  METHODS
  The Novel Therapies for Resistant Focal Segmental Glomerulosclerosis (FONT) project is a multicenter Phase I/II RCT designed to investigate the potential efficacy of novel therapies for resistant FSGS. Adalimumab and galactose will be evaluated against conservative therapy consisting of the combination of lisinopril, losartan and atorvastatin. The sample size is defined to assure that if one of the treatments has a superior response rate compared to that of the other treatments, it will be selected with high probability for further evaluation. Comparison of primary and secondary endpoints in each study arm will enable a choice to be made of which treatments are worthy of further study in future Phase III RCT.
  
  
  CONCLUSIONS
  This report highlights the key features of the FONT II RCT including the two-step outcome analysis that will expedite achievement of the study objectives. The proposed phase II study design will help to identify promising agents for further testing while excluding ineffective agents. This staged approach can help to prevent large expenditures on unworthy therapeutic agents in the management of serious but rare kidney diseases.
authors.affiliation: Cohen Children's Medical Center of New York, North Shore Long Island Jewish Health System, New Hyde Park, NY, USA. trachtma@lij.edu
authors.forename: Howard
authors.initials: H
authors.lastname: Trachtman
authors.forename: Suzanne
authors.initials: S
authors.lastname: Vento
authors.forename: Debbie
authors.initials: D
authors.lastname: Gipson
authors.forename: Larysa
authors.initials: L
authors.lastname: Wickman
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gassman
authors.forename: Melanie
authors.initials: M
authors.lastname: Joy
authors.forename: Virginia
authors.initials: V
authors.lastname: Savin
authors.forename: Michael
authors.initials: M
authors.lastname: Somers
authors.forename: Maury
authors.initials: M
authors.lastname: Pinsk
authors.forename: Tom
authors.initials: T
authors.lastname: Greene
mesh_terms: D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000069059:Atorvastatin; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D005690:Galactose / Q000009:adverse effects / Q000627:therapeutic use*; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy*; D006538:Heptanoic Acids / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D017706:Lisinopril / Q000009:adverse effects / Q000627:therapeutic use; D019808:Losartan / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D011758:Pyrroles / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D017706:Lisinopril; D000068879:Adalimumab; D019808:Losartan; D005690:Galactose