Clinical Trial: A Phase II, Repeat Dose, Proof of Mechanism Study of Losmapimod to Reduce Proteinuria in Patients With Focal Segmental Glomerulosclerosis (FSGS)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Study of Losmapimod to Reduce Proteinuria in Idiopathic Focal Segmental Glomerulosclerosis (FSGS)

Brief Summary: This is a single-arm, multicenter, open-label Phase II, proof-of-mechanism study to evaluate the efficacy, safety, tolerability and pharmacokinetics of losmapimod in approximately 21 subjects with primary (idiopathic) focal segmental glomerulosclerosis (FSGS) and substantive proteinuria as indicated by a Urinary protein/creatinine Up/c ratio >=2 gram/gram (g/g) or 24 hr urine protein >=2 g/day. Losmapimod will be orally administered twice daily over a 24-week treatment phase followed by a 12-week follow-up for safety and relapse assessments.

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome: Reduction in proteinuria at the end of treatment (>=16 weeks) [ Time Frame: From Baseline up to Week 24 ]

The reduction in proteinurea will be assessed by responder analysis. A Responder is defined as >=50 percent reduction in proteinuria (24 hour total protein) from baseline with a maintenance of renal function (>=70 percent of baseline Estimated Glomerular Filtration Rate [eGFR])


Original Primary Outcome: Reduction in proteinuria at the end of treatment (>=16 weeks) [ Time Frame: From Baseline up to Week 24 ]

The reduction in proteinurea will be assessed by responder analysis. A Responder is defined as >=50 percent reduction in proteinuria (Up/c ratio) from baseline with a maintenance of renal function (>=70 percent of baseline Estimated Glomerular Filtration Rate [eGFR])


Current Secondary Outcome:

  • Reduction in proteinuria at any time during treatment [ Time Frame: From Baseline up to Week 24 ]
    The reduction in proteinurea will be assessed by responder analysis. A Responder is defined as >=50 percent reduction in proteinuria (24 hour total protein) from baseline with a maintenance of renal function (>=70 percent of baseline eGFR)
  • Proteinuria responses [ Time Frame: From Baseline up to Week 24 ]
    Urine sample will be collected for evaluation of proteinuria responses including incidence of complete remissions which is defined as proteinuria 24 hour total protein <0.3 g/day and maintenance of >=70 percent of baseline eGFR throughout treatment period
  • Safety and tolerability of losmapimod [ Time Frame: From Baseline up to Week 36 ]
    Safety and tolerability assessments including: adverse events (AEs), serious adverse events (SAEs), subject withdrawals due to toxicities, changes in clinical laboratory values (liver function tests [LFTs], serum creatinine, eGFR, cystatin C) and vital signs
  • Pharmacokinetics (PK) of losmapimod and metabolite (GSK198602) [ Time Frame: Baseline (pre-dose, 1, 2, 4, and 6 hours post-dose), Week 2 (pre-dose and 2 hours post-dose), Weeks 4, 8, 16 and 24 at one of the post-dose times (0 to 2 hours/2 to 4 hours/4 to 6 hours/6 to 8 hours post-dose) ]
    Blood samples will be collected for the assessment of plasma exposure post first dose and area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC [0-t]) (7.5 milligram [mg]), area under the plasma concentration-time curve during a dosage interval (AUC[0-tau]) (7.5 mg and 15 mg), and maximum observed concentration (Cmax) (7.5 mg)
  • Reduction in proteinuria by assessment of Up/c (urine protein creatinine) ratio [ Time Frame: From Baseline up to Week 24 ]
    Up/c change from baseline will be used to confirm the findings of the total 24-hour urine protein.


Original Secondary Outcome:

  • Reduction in proteinuria at any time during treatment [ Time Frame: From Baseline up to Week 24 ]
    The reduction in proteinurea will be assessed by responder analysis. A Responder is defined as >=50 percent reduction in proteinuria (Up/c ratio) from baseline with a maintenance of renal function (>=70 percent of baseline eGFR)
  • Proteinuria responses [ Time Frame: From Baseline up to Week 24 ]
    Urine sample will be collected for evaluation of proteinuria responses including incidence of complete remissions which is defined as proteinuria Up/c <0.3 and maintenance of >=70 percent of baseline eGFR throughout treatment period
  • Safety and tolerability of losmapimod [ Time Frame: From Baseline up to Week 36 ]
    Safety and tolerability assessments including: adverse events (AEs), serious adverse events (SAEs), subject withdrawals due to toxicities, changes in clinical laboratory values (liver function tests [LFTs], serum creatinine, eGFR, cystatin C) and vital signs
  • Pharmacokinetics (PK) of losmapimod and metabolite (GSK198602) [ Time Frame: Baseline (pre-dose, 1, 2, 4, and 6 hours post-dose), Week 2 (pre-dose and 2 hours post-dose), Weeks 4, 8, 16 and 24 at one of the post-dose times (0 to 2 hours/2 to 4 hours/4 to 6 hours/6 to 8 hours post-dose) ]
    Blood samples will be collected for the assessment of plasma exposure post first dose and area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC [0-t]) (7.5 mg), area under the plasma concentration-time curve during a dosage interval (AUC[0-tau]) (7.5 mg and 15 mg), and maximum observed concentration (Cmax) (7.5 mg)


Information By: GlaxoSmithKline

Dates:
Date Received: November 27, 2013
Date Started: July 2014
Date Completion:
Last Updated: January 16, 2017
Last Verified: January 2017