Evaluation of Effect of TRC101 on Progression of Chronic Kidney Disease in Subjects With Metabolic Acidosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of TRC101 on the progression of chronic kidney disease (CKD) and to evaluate the safety profile of TRC101 in CKD patients with metabolic acidosis.

Detailed Description
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This is a randomized, double-blind, placebo-controlled trial. Eligible subjects will be randomized in a 1:1 ratio to TRC101 or placebo. The primary endpoint of the study will be progression of renal disease, defined by time to first occurrence of any event in the composite endpoint consisting of a confirmed ≥ 40% reduction in eGFR, end-stage renal disease (ESRD), and renal death. The study will terminate when the independent blinded Clinical Endpoint Adjudication Committee has positively adjudicated the targeted number of primary efficacy endpoint events. The maximum duration of follow-up for a randomized subject is anticipated to be approximately 6 years.

Official Title
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A Phase 3b, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of TRC101 in Delaying Chronic Kidney Disease Progression in Subjects With Metabolic Acidosis

Conditions
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Metabolic Acidosis, Chronic Kidney Disease

Intervention / Treatment
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* Drug: TRC101
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Estimated glomerular filtration rate (eGFR) 20 - 40 mL/min/1.73m^2. Serum bicarbonate 12 - 20 mEq/L. On maximum tolerated dose of ACE inhibitor and/or ARB. Exclusion Criteria: Acute metabolic acidosis. Anticipated dialysis or kidney transplant within 6 months. Recent acute kidney injury.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TRC101<br> | Drug: TRC101<br>* Oral, non-absorbed, polymeric hydrochloric acid binder<br>* Other names: Veverimer;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of chronic kidney disease | Time to first occurrence of: a confirmed ≥40% reduction in eGFR; ESRD; renal death. | Through study completion, up to approximately 6 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death (all-cause), ESRD or a confirmed ≥50% reduction in eGFR | Time to first occurrence of: death (all-cause); ESRD; a confirmed ≥50% reduction in eGFR. | Through study completion, up to approximately 6 years. | 
| Physical functioning (subjective) | Kidney Disease Quality of Life Physical Functioning Survey. | 18 months after randomization. | 
| Physical functioning (objective) | Repeated chair stand test. | 18 months after randomization. | 
| ESRD or renal death | Time to ESRD or renal death. | Through study completion, up to approximately 6 years. | 
| Primary outcome measure OR cardiovascular death | Time to first occurrence of: a confirmed ≥40% reduction in eGFR; ESRD; renal death; cardiovascular death. | Through study completion, up to approximately 6 years. | 
| Serum creatinine | Time to first occurrence of a confirmed doubling of serum creatinine. | Through study completion, up to approximately 6 years. | 
| ≥50% reduction in eGFR | Time to first occurrence of a confirmed ≥50% reduction in eGFR. | Through study completion, up to approximately 6 years. | 
| ≥40% reduction in eGFR | Time to first occurrence of a confirmed ≥40% reduction in eGFR. | Through study completion, up to approximately 6 years. | 
| All-cause hospitalization | Frequency of all-cause hospitalization. | Through study completion, up to approximately 6 years. | 
| Cardiovascular death | Time to cardiovascular death. | Through study completion, up to approximately 6 years. | 
| All-cause mortality | Time to all-cause mortality. | Through study completion, up to approximately 6 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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serum bicarbonate, renal outcomes, TRC101, eGFR, veverimer