An Open-Label, Long-term Study of GFB-887 in Patients With Glomerular Kidney Diseases

Study Overview
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Brief Summary
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This is an open-label Phase 2 study evaluating the long term safety and tolerability of GFB-887 in patients with focal segmental glomerulosclerosis (FSGS), and treatment-resistant minimal change disease (TR-MCD)

Detailed Description
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Participants will be enrolled from the ongoing GFB-887 multiple ascending dose trial. Participants will be transitioned to a 200 mg QD dose level regardless of the dose received in the previous study although the data review team (DRT) and Medical Monitor may elect to decrease or increase the dose to minimize adverse events or improve clinical efficacy. The DRT may also elect to change dosing levels due to emerging data on GFB-887. Participants will take GFB-887 once daily at home. A phone visit will be conducted at Week 4 and at Week 8 to assess safety and tolerability. Participants will return to the clinic for follow up visits at Weeks 12, 24, 36, 48, and every 24 weeks thereafter through approximately 3 years from the time of the participant's first dose to evaluate long-term safety and durability of response (for up to approximately 13 scheduled in-clinic visits).

Official Title
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An Open-Label, Long-term Study of GFB-887 in Patients With Glomerular Kidney Diseases

Conditions
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Nephritis, Kidney Diseases, Glomerulosclerosis, Focal Segmental Nephrosis, Lipoid Urologic Disease, Glomerulonephritis, Nephrosis

Intervention / Treatment
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* Drug: GFB-887


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with FSGS/TR-MCD who have completed the treatment phase from an interventional clinical study with GFB-887. Participants who were discontinued for rising proteinuria from a GFB-887 interventional study may be considered for enrollment following consultation with the Medical Monitor. Participants who enrolled in any other interventional study during the time between completion of the prior GFB-887 interventional study and this study may be considered for enrollment following consultation with the Medical Monitor. Exclusion Criteria: Participant is unable to take oral medications Participant has an unstable medical condition based on medical history, physical examination, laboratory tests, ECGs, vital signs or is otherwise unstable in the judgement of the Investigator which would pose a risk to the participant or interfere with study evaluation, procedures, or completion Evidence of significant hypersensitivity, intolerance, or allergy to any component of investigational product GFB-887

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label study extension
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 200 mg Dose Cohort<br>Participants who received GFB-887 or placebo in GFB-887-201 will receive GFB-887 at a daily dose level of 200 mg regardless of original dose level. | Drug: GFB-887<br>* GFB-887 is a potent, small molecule inhibitor of TRPC5.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events | Incidence and severity of adverse events | Approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent reduction in urine protein:creatinine ratio (UPCR) from baseline | Percent reduction in urine protein:creatinine ratio (UPCR) from baseline | Approximately 3 years | 
| Proportion of participants achieving modified partial remission status | Proportion of participants achieving modified partial remission status | Approximately 3 years | 
| Proportion of participants achieving complete remission status | Proportion of participants achieving complete remission status | Approximately 3 years | 
| Proportion of participants with a UPCR decrease of at least 30% from baseline | Proportion of participants with a UPCR decrease of at least 30% from baseline | Approximately 3 years | 
| Proportion of participants with a UPCR decrease of at least 40% from baseline | Proportion of participants with a UPCR decrease of at least 40% from baseline | Approximately 3 years | 
| Proportion of participants with a UPCR decrease of at least 50% from baseline | Proportion of participants with a UPCR decrease of at least 50% from baseline | Approximately 3 years | 
| Time to maximal percent reduction in UPCR from baseline | Time to maximal percent reduction in UPCR from baseline | Approximately 3 years | 
| Summary of plasma pharmacokinetic (PK) concentrations: Dose proportionality | Dose proportionality of GFB-887 | Approximately 3 years | 
| Summary of Plasma PK concentrations (AUCinf) | Area under the plasma concentration-time curve from time zero to infinity | Approximately 3 years | 
| Summary of Plasma PK concentrations (AUClast) | Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration | Approximately 3 years | 
| Summary of Plasma PK concentrations (Cmax) | Maximum observed plasma concentration | Approximately 3 years | 
| Changes in estimated glomerular filtration rate (eGFR) including slope | Glomerular filtration rate will be estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on serum creatinine | Approximately 3 years |