Efficacy and Safety of Atacicept in IgA Nephropathy

Study Overview
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Brief Summary
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This main purpose of this study was to evaluate the safety, tolerability, dose response and efficacy of Atacicept in participants with IgA nephropathy and persistent proteinuria. The study hypothesis was that treatment with Atacicept would reduce proteinuria compared to placebo.

Official Title
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A Phase II Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Atacicept in IgA Nephropathy

Conditions
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IgA Nephropathy

Intervention / Treatment
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* Drug: Placebo
* Drug: Atacicept 25 mg
* Drug: Atacicept 75 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Greater than or equal to (>=)18 years of age Biopsy-proven Immunoglobulin (IgA) nephropathy Urine Protein to Creatinine Ratio (UPCR) >= 0.75 and <= 6 milligram per milligram (mg/mg) during screening Stable and optimal dose of Angiotensin converting enzyme (ACE) inhibitor and/or angiotensin II receptor blockers (ARB) at least 8 weeks prior to screening Exclusion Criteria: Concomitant significant renal disease other than IgA nephropathy IgA nephropathy with significant glomerulosclerosis or cortical scarring Diagnosis of Henoch-Schonlein purpura Failure to meet estimated glomerular filtration rate (eGFR) and biopsy requirement criteria Serum IgG below 6 grams per liter (g/L) Use of cyclophosphamide ever or use of other immunosuppressants or systemic corticosteroids within 4 months Active infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks History, or current diagnosis, of active tuberculosis (TB), or untreated latent TB infection History of or positive HIV and/or positive for hepatitis B or Hepatitis C at screening History of malignancy Nursing or pregnancy Any condition, including any uncontrolled disease state other than IgA nephropathy

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: Placebo<br> | Drug: Placebo<br>* Participants received placebo matched to Atacicept once weekly as subcutaneous (SC) injection during this study up to a maximum of 72.1 weeks.<br>|
| Experimental: Atacicept 25 mg<br> | Drug: Atacicept 25 mg<br>* Participants received 25 milligrams (mg) of Atacicept once weekly as SC injection during this study up to a maximum of 73.6 weeks.<br>|
| Experimental: Atacicept 75 mg<br> | Drug: Atacicept 75 mg<br>* Participants received 75 mg of Atacicept once weekly as SC injection during this study up to a maximum of 74.1 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs), Adverse Event of Special Interest (AESIs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death | Adverse Event (AE): any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: AEs that developed or worsened/became serious during on-treatment period (time from the first dose of study drug up to the end of study [Week 96]). TEAEs included serious AEs and non- serous AEs. AESIs included infections, cardiac failure, cardiomyopathy/ ischemic heart disease, hypersensitivity reaction (including anaphylactic/anaphylactoid shock conditions, asthma/bronchospasm, and angioedema), injection site reactions (ISRs) and demyelinating disorders. Investigator or his /her designee assessed ISRs as local reactions (redness, bruising, swelling, induration and itching). | Baseline up to 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Atacicept Concentrations | Serum Atacicept Concentrations was to be performed; however; as per changed in planned analysis the outcome measure related to pharmacokinetic parameters was not assessed. | Week 0 Day 1 (pre-dose), Weeks 1, 2, 4, 8, 12, 16, 24, 40, 48, 72, Early Termination (up to Week 72) and Post-treatment (PT) Follow Up (FU) Weeks 4, 12 and 24 | 
| Change From Baseline Levels in Serum Immunoglobulin A (IgA) | The change in serum levels of IgA from baseline was reported. | Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, Early Termination (up to Week 72) and PT FU Weeks 4, 12 and 24 | 
| Change From Baseline Levels in Serum Iimmunoglobulin G (IgG) | The change in serum levels of IgG from baseline was reported. | Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, Early Termination (up to Week 72) and PT FU Weeks 4, 12 and 24 | 
| Change From Baseline Levels in Serum Immunoglobulin M (IgM) | The change in serum levels of IgM from baseline was reported. | Baseline, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, Early Termination (up to Week 72) and at PT FU Weeks 4, 12 and 24 | 
| Change From Baseline in Serum Galactose Deficient-IgA1 (Gd-IgA1) Levels | The change in serum Gd-IgA1 from baseline was reported. | Baseline, Weeks 4, 12, 24, 48, 72, Early Termination (up to Week 72 and at PT FU Weeks 12 and 24 | 
| Change From Baseline in Serum Complement C3 and C4 Levels | The change in serum component C3 and C4 from baseline were reported. | Baseline, Week 12, 24, 48, 72, Early Termination (up to Week 72) and at PT FU Weeks 12 and 24 | 
| Change From Baseline in Immune Cell Subsets by Flow Cytometry Analysis | Change from baseline in immune cell subsets included total T cells, helper T cells, cytotoxic T cells, total B cells (assay with [AW] CD45 or assay without [AWO] CD45), mature naïve B cells, memory B cells, plasma cells, plasma blasts, and natural killer (NK) cells and were reported. Analysis was performed by flow cytometry analysis. | Baseline, Weeks 4, 12, 24, 48, 72, Early Termination (up to Week 72) and at PT FU Week 24 | 
| Change From Baseline in Urinary IgG, IgA, and IgM Levels | Urinary IgG, IgA and IgM levels to be measured by Immuno-Electrophoresis. | Baseline (Day1), Weeks 24, 48 and Early Termination (up to earlier than Week 72) | 
| Percentage of Participants With Positive Anti-Drug Antibody (ADA) | Percentage of participants with positive ADA were reported. | Baseline up to safety follow-up (96 weeks) | 
| Percentage of Participants With Clinical Significant Abnormalities in Laboratory Assessments | Laboratory investigation included hematology, biochemistry, urinalysis and Urine sediment analysis. Clinical significance was to be decided by the investigator. | Baseline up to safety follow-up (96 weeks) | 
| Percentage of Participants With Clinical Significant Abnormalities in Vital Signs | Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate, weight and height. The systolic and diastolic blood pressure and pulse rate was measured after the participants have in a rested at least 3 minutes in seated position. Clinical significance was to be decided by the investigator. | Baseline up to safety follow-up (96 weeks) | 
| Percentage of Participants With Clinical Significant Abnormalities in 12-Lead Electrocardiograms (ECGs) | 12-lead ECG were recorded after the participants have rested for at least 15 minutes in supine position. Clinically significance was decided by the investigator. The number of participants with clinically significant abnormalities in 12-lead ECG were reported. | Baseline up to safety follow-up (96 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atacicept, IgA Nephropathy, Berger´s disease, Glomerulonephritis, Proteinuria