Efficacy of galactose and adalimumab in patients with resistant focal segmental glomerulosclerosis

report of the font clinical trial group

Howard Trachtman, Suzanne Vento, Emily Herreshoff, Milena Radeva, Jennifer Gassman, Daniel T. Stein, Virginia J. Savin, Mukut Sharma, Jochen Reiser, Changli Wei, Michael Somers, Tarak Vastava, Debbie S. Gipson

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)111
Number of pages1
JournalBMC Nephrology
Volume16
DOIs
StatePublished - Jul 22 2015

Fingerprint

Focal Segmental Glomerulosclerosis
Galactose
Clinical Trials
Proteinuria
Glomerular Filtration Rate
Therapeutics
Adalimumab
Urokinase Plasminogen Activator Receptors
Lisinopril
Phase II Clinical Trials
Losartan
Immunosuppressive Agents
Rare Diseases
Documentation
Sample Size
Chronic Kidney Failure
Permeability
Creatinine
Adrenal Cortex Hormones
Fibrosis

ASJC Scopus subject areas

  • Nephrology

Cite this

Efficacy of galactose and adalimumab in patients with resistant focal segmental glomerulosclerosis : report of the font clinical trial group. / Trachtman, Howard; Vento, Suzanne; Herreshoff, Emily; Radeva, Milena; Gassman, Jennifer; Stein, Daniel T.; Savin, Virginia J.; Sharma, Mukut; Reiser, Jochen; Wei, Changli; Somers, Michael; Vastava, Tarak; Gipson, Debbie S.

In: BMC Nephrology, Vol. 16, 22.07.2015, p. 111.

Research output: Contribution to journalArticle

Trachtman, H, Vento, S, Herreshoff, E, Radeva, M, Gassman, J, Stein, DT, Savin, VJ, Sharma, M, Reiser, J, Wei, C, Somers, M, Vastava, T & Gipson, DS 2015, 'Efficacy of galactose and adalimumab in patients with resistant focal segmental glomerulosclerosis: report of the font clinical trial group', BMC Nephrology, vol. 16, pp. 111. https://doi.org/10.1186/s12882-015-0094-5
Trachtman, Howard ; Vento, Suzanne ; Herreshoff, Emily ; Radeva, Milena ; Gassman, Jennifer ; Stein, Daniel T. ; Savin, Virginia J. ; Sharma, Mukut ; Reiser, Jochen ; Wei, Changli ; Somers, Michael ; Vastava, Tarak ; Gipson, Debbie S. / Efficacy of galactose and adalimumab in patients with resistant focal segmental glomerulosclerosis : report of the font clinical trial group. In: BMC Nephrology. 2015 ; Vol. 16. pp. 111.
@article{bf60c44bff83485c83df8223b1462f2f,
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.",
author = "Howard Trachtman and Suzanne Vento and Emily Herreshoff and Milena Radeva and Jennifer Gassman and Stein, {Daniel T.} and Savin, {Virginia J.} and Mukut Sharma and Jochen Reiser and Changli Wei and Michael Somers and Tarak Vastava and Gipson, {Debbie S.}",
year = "2015",
month = "7",
day = "22",
doi = "10.1186/s12882-015-0094-5",
language = "English (US)",
volume = "16",
pages = "111",
journal = "BMC Nephrology",
issn = "1471-2369",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Efficacy of galactose and adalimumab in patients with resistant focal segmental glomerulosclerosis

T2 - report of the font clinical trial group

AU - Trachtman, Howard

AU - Vento, Suzanne

AU - Herreshoff, Emily

AU - Radeva, Milena

AU - Gassman, Jennifer

AU - Stein, Daniel T.

AU - Savin, Virginia J.

AU - Sharma, Mukut

AU - Reiser, Jochen

AU - Wei, Changli

AU - Somers, Michael

AU - Vastava, Tarak

AU - Gipson, Debbie S.

PY - 2015/7/22

Y1 - 2015/7/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85016924285&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016924285&partnerID=8YFLogxK

U2 - 10.1186/s12882-015-0094-5

DO - 10.1186/s12882-015-0094-5

M3 - Article

VL - 16

SP - 111

JO - BMC Nephrology

JF - BMC Nephrology

SN - 1471-2369

ER -