BCX9930 for the Treatment of C3G, IgAN, and PMN (RENEW)

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and therapeutic potential of BCX9930 in participants with C3G, IgAN, or PMN.

Detailed Description
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This is an open-label, multicenter, proof-of-concept study to evaluate the safety, tolerability, and therapeutic potential of BCX9930 administered for 52 weeks in adult (≥ 18 years old) participants with either C3G, IgAN, or PMN. All participants will be enrolled into one of the three parallel treatment cohorts based on diagnosis of C3G, IgAN, or PMN and will receive BCX9930 for the 52-week treatment period.

Official Title
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An Open-Label, Safety, Tolerability, and Proof-of-Concept Study of Oral BCX9930 Therapy in Subjects With C3G, IgAN, or PMN

Conditions
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Complement 3 Glomerulopathy, Immunoglobulin A Nephropathy, Membranous Nephropathy

Intervention / Treatment
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* Drug: BCX9930


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged ≥ 18 years old Body weight ≥ 40 kg Primary diagnosis of C3G, IgAN, or PMN confirmed by central pathology review An eGFR ≥ 50 mL/min/1.73 m2 (or ≥ 30 mL/min/1.73 m2 after DMC recommendation) Receiving treatment with a stable, maximum recommended or maximum tolerated dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) for at least 60 days prior to the Day 1 Visit Documentation of current vaccinations against Neisseria meningitidis and Streptococcus pneumoniae or willingness to start vaccination series Exclusion Criteria: Known congenital deficiency of C1s, C1r, C1q, C2, or C4 History of hematopoietic cell transplant or solid organ transplant or anticipated candidate for transplantation Myocardial infarction or cerebrovascular accident within 30 days prior to screening, or current and uncontrolled clinically significant cardiovascular or cerebrovascular condition History of malignancy within 5 years prior to the screening visit Active serious bacterial, viral, or fungal infection or any other serious infection within 14 days of screening Treatment with any systemic immunosuppressive or immunomodulatory therapy within 90 days OR anti-CD20 antibody therapies (eg, rituximab) within 180 days prior to the screening visit Treatment with renin inhibitors (eg, aliskiren) or sodium-glucose-cotransporter 2 (SGLT2) inhibitors within 60 days prior to Day 1

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Three parallel treatment cohorts based on diagnosis of C3G, IgAN, or PMN. All eligible participants will receive open-label BCX9930.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: C3G cohort<br>Approximately 14 eligible participants with C3G will be enrolled. | Drug: BCX9930<br>* Administered orally at a dose of 200 mg twice daily for the first 2 weeks, then 400 mg twice daily<br>|
| Other: IgAN cohort<br>Approximately 14 eligible participants with IgAN will be enrolled. | Drug: BCX9930<br>* Administered orally at a dose of 200 mg twice daily for the first 2 weeks, then 400 mg twice daily<br>|
| Other: PMN cohort<br>Approximately 14 eligible participants with PMN will be enrolled. | Drug: BCX9930<br>* Administered orally at a dose of 200 mg twice daily for the first 2 weeks, then 400 mg twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in 24-hour urine protein-to-creatinine ratio (uPCR) |  | Week 12, 24, 36, 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with a uPCR response: ≥ 50% reduction from baseline, ≤ 500 mg/g, or ≤ 200 mg/g |  | Week 12, 24, 36, 52 | 
| Percent change from baseline in 24-hour urinary protein excretion |  | Week 12, 24, 36, 52 | 
| Change from baseline in estimated glomerular filtration rate |  | Week 12, 24, 36, 52 | 
| Change from baseline in serum albumin |  | Week 12, 24, 36, 52 | 
| Proportion of subjects with protein ≥ 3.5 g in a 24-hour urine collection and serum albumin ≤ 2.5 g/dL |  | Week 12, 24, 36, 52 | 
| Proportion of subjects with a morphologic response |  | Week 24 | 
| Treatment-emergent adverse event and serious adverse event |  | through Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCX9930, factor D inhibitor, oral therapy, Complement 3 Glomerulopathy, Immunoglobulin A Nephropathy, Primary Membranous Nephropathy