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

Inclusion Criteria

• Subject is between 18 and 70 years of age inclusive.
• Subject has a clinical diagnosis of primary (idiopathic) focal segmental glomerulosclerosis (FSGS) as verified by renal biopsy. This must be confirmed by independent review of the histopathology report and/or biopsy specimen(s) by the study central pathologist.
• Subject will have substantive proteinuria, as indicated by a spot Up/c>=2g/g or 24 hour urine total protein >=2g/day.
• A female subject is eligible to participate if she is of non-childbearing potential; criteria to be considered of 'non-childbearing potential' as described in the protocol.
• A female subject is eligible to participate if she is of child-bearing potential. Females of child-bearing potential must agree to use two of the approved contraception methods listed in the protocol from 14 days before the first dose of study drug until 30 days after the last dose of study drug. Only females of child-bearing potential with negative pregnancy test, as determined by serum human chorionic gonadotropin (hCG) test at screening and urine hCG test prior to dosing at baseline visit and during the study at the indicated times, will be administered losmapimod.
• Subject is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form and is willing and able to return for all study visits.

Exclusion Criteria

• Subject has received a live attenuated vaccine within 6 weeks of first study treatment.
• Subject has collapsing FSGS lesion.
• Subject has secondary FSGS or renal impairment from a condition that is not FSGS. Causes of secondary FSGS include but are not limited to: Drugs and toxins: Analgesics, heroin, cocaine and pamidronate; Infectious or parasitic diseases: Hepatitis B, Hepatitis C, HIV (known as HIV-Associated Nephropathy), parvovirus; Adaptive structural-functional response likely mediated by glomerular hypertrophy/hyperfiltration: Hemodynamic factors - With reduced renal mass: solitary kidney, renal allograft, renal dysplasia, renal agenesis, oligomeganephronia, segmental hypoplasia, vesicoureteric reflux; Hemodynamic causes - Without reduced renal mass: sickle cell nephropathy, congenital cyanotic heart disease, hypertension; Malignancies: Lymphomas and other malignancies; for skin or cervical cancer consult medical monitor; Diabetic Nephropathy; Other forms of glomerular nephropathy: focal proliferative glomerulonephritis (IgA nephropathy, lupus, nephritis, pauci-immune focal necrotizing and crescentic glomerulonephritis), hereditary nephritis, hypertensive arterionephrosclerosis, membranous glomerulopathy, thrombotic microangiopathies; Miscellaneous: Alport syndrome, sarcoidosis, radiation nephritis; Genetic forms of FSGS (e.g. patient is known to carry FSGS causing genetic mutation).
• History of congestive heart failure.
• History of diabetes mellitus type 1 or 2.
• History of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
• Clinically significant systemic illness or infection within the last 28 days (e.g. chronic persistent or acute infection) that is likely to result in deterioration of the subject's condition or affect the subject's safety during the study.
• Any condition or situation, including clinically significant abnormalities in screening laboratory assessments (not related to the disease), which in the opinion of the Investigator could confound the results of the study or put the subject at undue risk.
• History of sensitivity or intolerance to the study treatment (i.e. losmapimod), or a history of drug or other allergy that in the opinion of the Investigator or GSK Medical Monitor contraindicates participation.
• Estimated GFR = 2xUpper Limit of Normal (ULN); alkaline phosphatase and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin =450 milliseconds (msec) (machine or ma