Atacicept in Subjects With IgA Nephropathy

Study Overview
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Brief Summary
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A Phase 3 Study with Atacicept in Subjects With IgA Nephropathy (ORIGIN 3)

Detailed Description
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This is a multi-part study comprising of the original Phase 2b study (active, no longer recruiting) and the addition of a separate pivotal Phase 3 study (active, recruiting). After the completion of the primary results for the Ph 2b dose ranging study, the pivotal study (active, recruiting) will evaluate the efficacy and safety of atacicept compared to placebo in reducing proteinuria in subjects with IgAN and persistent proteinuria despite being on a maximally tolerated dose (MTD) of a RASi. Safety, eGFR, serum immunoglobulins and Gd-IgA1 will also be clinically assessed. The clinical study is comprised of a 104wk double-blind treatment period, followed by a 52wk open-label treatment period and a 26wk safety follow-up period. The UPCR primary endpoint will be assessed after the first 200 patients are randomized.

Official Title
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A Phase 2b/3, Multi-part, Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Atacicept in Subjects With IgA Nephropathy (IgAN)

Conditions
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IgA Nephropathy, Berger Disease

Intervention / Treatment
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* Biological: Atacicept
* Other: Placebo to match Atacicept


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Must have the ability to understand and sign a written informed consent form Male or female of ≥18 years of age Total urine protein excretion ≥1.0 g per 24-hour or urine protein to creatinine ratio (UPCR) ≥1.0 mg/mg based on a 24-hour urine sample during the Screening Period Diagnosis of IgAN as demonstrated by renal biopsy conducted within 10 years eGFR ≥ 30 mL/min/1.73 m2, as per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. On a stable prescribed regimen of RAASi for at least 12 weeks that is at the maximum labeled or tolerated dose at Screening Systolic blood pressure ≤150 mmHg and diastolic blood pressure ≤90 mmHg Key Exclusion Criteria: IgAN secondary to another condition (e.g., liver cirrhosis), or other causes of mesangial IgA deposition including IgA vasculitis (i.e., Henoch-Schonlein purpura), systemic lupus erythematosus (SLE), dermatitis herpetiformis, ankylosing spondylitis Total urine protein excretion ≥ 5g per 24-hour or urine protein to creatinine ratio (UPCR) ≥ 5 mg/mg based on a 24-hour urine sample during the Screening Period Evidence of rapidly progressive glomerulonephritis (loss of ≥ 50% of eGFR within 3 months of screening) Evidence of nephrotic syndrome within 6 months of screening (serum albumin <30g/L in association with UPCR >3.5 mg/mg Renal or other organ transplantation prior to, or expected during the study Concomitant chronic renal disease in addition to IgAN Uncontrolled diabetes, defined as hemoglobin-A1c (HbA1c) >7.5% at screening History of tuberculosis (TB), untreated latent TB infection (LTBI), or evidence of active TB determined by a positive Quantiferon test Participation in the Phase 2b (Parts A and B) study or any previous treatment with atacicept

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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atacicept Dose 150mg<br>Atacicept 150mg once weekly subcutaneous (SC) injections | Biological: Atacicept<br>* Once weekly subcutaneous (SC) injections by prefilled syringe<br>* Other names: VT-001;|
| Placebo Comparator: Placebo to match Atacicept (Part C/D)<br>Placebo to match Atacicept once weekly subcutaneous (SC) injection | Other: Placebo to match Atacicept<br>* Once weekly subcutaneous (SC) injections by prefilled syringe<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in urine protein to creatinine ratio (UPCR) | UPCR based on 24 hour urine collection | 36 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized rate of change in estimated glomerular filtration rate (eGFR) | eGFR calculated by CKD-EPI formula | 52 and 104 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Berger Disease, Berger's Disease, IGA Glomerulonephritis, IGA Nephropathy, Iga Nephropathy 1, Immunoglobulin A Nephropathy Nephritis, IGA Type Nephropathy, IGA