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2015 ; 16
(ä): 111
Nephropedia Template TP
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Efficacy of galactose and adalimumab in patients with resistant focal segmental
glomerulosclerosis: report of the font clinical trial group
#MMPMID26198842
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
BMC Nephrol
2015[Jul]; 16
(ä): 111
PMID26198842
show ga
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.
|Adalimumab/*therapeutic use
[MESH]
|Adolescent
[MESH]
|Adrenal Cortex Hormones/therapeutic use
[MESH]
|Adult
[MESH]
|Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use
[MESH]