A Phase II Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Atacicept in IgA Nephropathy
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- IgA Nephropathy
- Sponsor
- EMD Serono Research & Development Institute, Inc.
- Enrollment
- 16
- Locations
- 18
- Primary Endpoint
- 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
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Placebo
Intervention: Placebo
Atacicept 25 mg
Intervention: Atacicept 25 mg
Atacicept 75 mg
Intervention: Atacicept 75 mg
Outcomes
Primary Outcomes
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
Time Frame: 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 Outcomes
- 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)
- 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)
- 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)
- Percentage of Participants With Clinical Significant Abnormalities in 12-Lead Electrocardiograms (ECGs)(Baseline up to safety follow-up (96 weeks))
- Change From Baseline in Urinary IgG, IgA, and IgM Levels(Baseline (Day1), Weeks 24, 48 and Early Termination (up to earlier than Week 72))
- 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)
- 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)
- Percentage of Participants With Clinical Significant Abnormalities in Laboratory Assessments(Baseline up to safety follow-up (96 weeks))
- 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)
- 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)
- Percentage of Participants With Positive Anti-Drug Antibody (ADA)(Baseline up to safety follow-up (96 weeks))
- Percentage of Participants With Clinical Significant Abnormalities in Vital Signs(Baseline up to safety follow-up (96 weeks))