Efficacy and Safety of Atacicept in IgA Nephropathy
- Conditions
- IgA Nephropathy
- Interventions
- Registration Number
- NCT02808429
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 16
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Atacicept 75 mg Atacicept 75 mg - Placebo Placebo - Atacicept 25 mg Atacicept 25 mg -
- Primary Outcome Measures
Name Time Method 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 Baseline up to 96 weeks 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).
- Secondary Outcome Measures
Name Time Method Serum Atacicept Concentrations 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 Serum Atacicept Concentrations was to be performed; however; as per changed in planned analysis the outcome measure related to pharmacokinetic parameters was not assessed.
Change From Baseline in Serum Galactose Deficient-IgA1 (Gd-IgA1) Levels Baseline, Weeks 4, 12, 24, 48, 72, Early Termination (up to Week 72 and at PT FU Weeks 12 and 24 The change in serum Gd-IgA1 from baseline was reported.
Change From Baseline in Serum Complement C3 and C4 Levels Baseline, Week 12, 24, 48, 72, Early Termination (up to Week 72) and at PT FU Weeks 12 and 24 The change in serum component C3 and C4 from baseline were reported.
Percentage of Participants With Clinical Significant Abnormalities in 12-Lead Electrocardiograms (ECGs) Baseline up to safety follow-up (96 weeks) 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.
Change From Baseline in Urinary IgG, IgA, and IgM Levels Baseline (Day1), Weeks 24, 48 and Early Termination (up to earlier than Week 72) Urinary IgG, IgA and IgM levels to be measured by Immuno-Electrophoresis.
Change From Baseline Levels in Serum Immunoglobulin A (IgA) 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 The change in serum levels of IgA from baseline was reported.
Change From Baseline Levels in Serum Iimmunoglobulin G (IgG) 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 The change in serum levels of IgG from baseline was reported.
Percentage of Participants With Clinical Significant Abnormalities in Laboratory Assessments Baseline up to safety follow-up (96 weeks) Laboratory investigation included hematology, biochemistry, urinalysis and Urine sediment analysis. Clinical significance was to be decided by the investigator.
Change From Baseline Levels in Serum Immunoglobulin M (IgM) 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 The change in serum levels of IgM from baseline was reported.
Change From Baseline in Immune Cell Subsets 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 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.
Percentage of Participants With Positive Anti-Drug Antibody (ADA) Baseline up to safety follow-up (96 weeks) Percentage of participants with positive ADA were reported.
Percentage of Participants With Clinical Significant Abnormalities in Vital Signs Baseline up to safety follow-up (96 weeks) 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.
Trial Locations
- Locations (18)
Ohio State University Clinical Trials Management Office - Ohio State CTMO Parent
🇺🇸Columbus, Ohio, United States
Southeastern Clinical Research Institute, LLC
🇺🇸Augusta, Georgia, United States
California Institute of Renal Research - Chula Vista Location
🇺🇸Chula Vista, California, United States
Colorado Kidney Care PC - Dr. Marder
🇺🇸Denver, Colorado, United States
GA Nephrology Associates
🇺🇸Lawrenceville, Georgia, United States
The Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Northeast Clinical Research Center, LLC
🇺🇸Bethlehem, Pennsylvania, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Brookview Hills Research Associates, LLC
🇺🇸Winston-Salem, North Carolina, United States
Nephrotex Research Group
🇺🇸Dallas, Texas, United States
Providence Sacred Heart Medical Center & Children's Hospital
🇺🇸Spokane, Washington, United States
University Hospitals of Leicester NHS Trust - ULTIMATE PARENT
🇬🇧Leicester, United Kingdom
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Juntendo University Hospital - Dept of Nephrology/Hypertension
🇯🇵Bunkyo-ku, Japan
Southeast Renal Research Institute
🇺🇸Chattanooga, Tennessee, United States
Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
AKDHC Medical Research Services, LLC.
🇺🇸Glendale, Arizona, United States