Open-Label Study to Evaluate Safety and Efficacy of CCX168 in Subjects With IGA Nephropathy on Stable RAAS Blockade

Study Overview
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Brief Summary
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The primary safety objective of this study is to evaluate the safety and tolerability of CCX168 in subjects with IgAN on background supportive therapy with a maximally tolerated dose of RAAS blockade. The primary efficacy objective is to evaluate the efficacy of CCX168 based on an improvement in proteinuria.

Official Title
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An Open-Label Phase 2 Study to Evaluate the Safety and Efficacy of CCX168 in Subjects With Immunoglobulin A Nephropathy on Stable RAAS Blockade

Conditions
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Immunoglobulin A Nephropathy

Intervention / Treatment
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* Drug: CCX168


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of Immunoglobulin A nephropathy estimated glomerular filtration rate >60 mL/min/1.73 m2 Proteinuria (first morning urinary protein:creatinine ratio >1g/g creatinine) Key Exclusion Criteria: Severe renal disease Pregnant or nursing Proteinuria >8g/g creatinine or >8g/day Systemic manifestations of Henoch-Schonlein purpura within 2 years prior Patients with Immunoglobulin A nephropathy deemed secondary to underlying disease Biopsy reported severe crescentic Immunoglobulin A nephropathy History of treatment with glucocorticoids, cyclophosphamide, azathioprine, mycophenolate mofetil, or any biologic immunomodulatory agent with 24 weeks prior History of clinically significant cardiac conditions History of cancer within 5 years prior Any infection requiring antibiotic treatment that has not cleared prior to study start

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CCX168 (Avacopan)<br>CCX168 (Avacopan) plus stable dose of RAAS blocker | Drug: CCX168<br>* CCX168 30 mg, twice daily (b.i.d.) orally for 84 days (12 weeks). The CCX168 dose was taken in the morning, optimally within one hour after breakfast, and in the evening, optimally within one hour after dinner.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Slope of First Morning Urinary PCR From the 8-week RAAS Blocker run-in Period to the 12-week CCX168 Treatment Period | The mean change in the slope of the urinary protein:creatinine ratio (UPCR, in mg/g/week) between the 8-week run-in period and the 12-week treatment period | Week -8 to -1 (Run-in period) and Week 1 to 12 (treatment period) | 
| Number of Participants With AE's | Acronyms use: Adverse Events (AE's) Serious Adverse Events (SAE's) | Day 0 - Day 169 (throughout the trial) | 
| Severity of Adverse Events (AE's) | Acronyms use: Adverse Events (AE's) Serious Adverse Events (SAE's) | Day 0 - Day 169 (throughout the trial) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Achieving Renal Response From Baseline to Day 85 | Renal Response defined as an improvement in proteinuria based on a decrease from baseline to Day 85 in proteinuria to a level <300 mg/g creatinine and maintaining eGFR within 15% of baseline. | Baseline and Day 85 | 
| Proportion of Subjects Achieving a Partial Renal Response From Baseline to Day 85 | A partial renal response, defined as an improvement in proteinuria based on a decrease from baseline to Day 85 in proteinuria to a level <1 g/g creatinine and maintaining eGFR within 15% of baseline. | Baseline and Day 85 | 
| Change From Baseline to Day 85 in Vital Signs |  | Baseline to day 85 | 
| Change in Systolic Blood Pressure From Baseline to Day 85 |  | Baseline to day 85 | 
| Change in Diastolic Blood Pressure From Baseline to Day 85 |  | Baseline to day 85 | 
| Change in Temperature From Baseline to Day 85 |  | Baseline to day 85 | 
| Change in Weight From Baseline to Day 85 |  | Baseline to day 85 |