Safety and Efficacy of AT-1501 in Patients With IgA Nephropathy (IgAN)

Study Overview
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Brief Summary
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This is a phase 2a, multicenter, open-label study designed to evaluate the safety and efficacy of AT-1501 in patients with biopsy proven IgAN and at least 0.75 g/24 hours of protein in their urine at the time of screening.

Detailed Description
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Phase 2a, multicenter, open-label study designed to evaluate the safety and efficacy of AT-1501 in patients with biopsy proven IgAN and at least 0.75 g/24 hours of protein in their urine at the time of Screening. Up to 42 eligible patients will receive one of 2 doses of AT-1501. All patients are scheduled to receive AT-1501 by intravenous infusion every 3 weeks for approximately 2 years.

Official Title
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A Phase 2a, Multicenter, Open-Label Study to Evaluate the Safety and Efficacy of AT-1501 in Patients With IgA Nephropathy

Conditions
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IgA Nephropathy, IgAN

Intervention / Treatment
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* Drug: AT-1501


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years of age Biopsy proven IgAN Urine protein ≥ 0.75g/24 hours at Screening despite optimization with ACE inhibitors or angiotensin receptor blockers (ARB) eGFR ≥ 45 mL/min per 1.73 m2 or eGFR < 45 mL/min per 1.73 m2 and ≥ 30 mL/min per 1.73 m2 with a kidney biopsy within 2 years of Screening showing < 50% tubulointerstitial fibrosis Agree to comply with contraception requirements during and for 90 days after study completion. Exclusion Criteria: Any secondary IgAN as defined by the investigator Patients who have undergone a kidney transplant Any history of kidney disease other than IgAN Any history of diabetes (Type 1 or Type 2) Seated blood pressure > 140 mmHg (systolic) or > 90 mmHg (diastolic) at the Screening Visit. Patients must be on a stable dose and regimen of an ACE inhibitor or ARB for at least 90 days Pregnancy or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>AT-1501 10mg/kg Arm A will receive 10 mg/kg of AT-1501 every 3 weeks for up to 93 weeks for a total of 32 infusions. | Drug: AT-1501<br>* AT-1501 monoclonal antibody targeting CD40L given as an IV infusion<br>|
| Experimental: Arm B<br>AT-1501 5mg/kg Arm B will receive 5 mg/kg of AT-1501 every 3 weeks for up to 93 weeks for a total of 32 infusions | Drug: AT-1501<br>* AT-1501 monoclonal antibody targeting CD40L given as an IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - change in participants UPCR | The change in 24-hour urine protein to creatinine ratio (UPCR) from baseline to 24 weeks | Up to 24 weeks | 
| Safety- Number of participants with treatment related adverse events | Incidence of serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), and AEs of special interest (AEoSI) | Through study completion, an average of 100 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in eGFR slope | The change in eGFR slope from baseline to 96 weeks | Baseline- 96 weeks | 
| Change in urine protein excretion (mg/mg) | The change in urine protein excretion over time | Up to 96 weeks | 
| Development of Anti drug Antibodies (ADAs) | The percentage of participants who develop ADAs | Up to 96 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgA Nephropathy, IgAN, AT-1501, CD40L, Monoclonal antibody, Proteinuria, eGFR, UPCR