Clinical trial NCT02808429: Efficacy and Safety of Atacicept in IgA Nephropathy
Official title: A Phase II Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Atacicept in IgA Nephropathy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: IgA Nephropathy
Keywords: Atacicept
IgA Nephropathy
Berger´s disease
Glomerulonephritis
Proteinuria
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2016-06-21
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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
* Nursing or pregnancy
* Any condition, including any uncontrolled disease state other than IgA nephropathy

Primary outcomes:
measure: 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
timeFrame: Baseline up to 96 weeks
Secondary outcomes:
measure: Serum Atacicept Concentrations
timeFrame: 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
measure: Change From Baseline Levels in Serum Immunoglobulin A (IgA)
timeFrame: 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
measure: Change From Baseline Levels in Serum Iimmunoglobulin G (IgG)
timeFrame: 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
measure: Change From Baseline Levels in Serum Immunoglobulin M (IgM)
timeFrame: 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
measure: Change From Baseline in Serum Galactose Deficient-IgA1 (Gd-IgA1) Levels
timeFrame: Baseline, Weeks 4, 12, 24, 48, 72, Early Termination (up to Week 72 and at PT FU Weeks 12 and 24
measure: Change From Baseline in Serum Complement C3 and C4 Levels
timeFrame: Baseline, Week 12, 24, 48, 72, Early Termination (up to Week 72) and at PT FU Weeks 12 and 24
measure: Change From Baseline in Immune Cell Subsets by Flow Cytometry Analysis
timeFrame: Baseline, Weeks 4, 12, 24, 48, 72, Early Termination (up to Week 72) and at PT FU Week 24
measure: Change From Baseline in Urinary IgG, IgA, and IgM Levels
timeFrame: Baseline (Day1), Weeks 24, 48 and Early Termination (up to earlier than Week 72)
measure: Percentage of Participants With Positive Anti-Drug Antibody (ADA)
timeFrame: Baseline up to safety follow-up (96 weeks)
measure: Percentage of Participants With Clinical Significant Abnormalities in Laboratory Assessments
timeFrame: Baseline up to safety follow-up (96 weeks)
measure: Percentage of Participants With Clinical Significant Abnormalities in Vital Signs
timeFrame: Baseline up to safety follow-up (96 weeks)
measure: Percentage of Participants With Clinical Significant Abnormalities in 12-Lead Electrocardiograms (ECGs)
timeFrame: Baseline up to safety follow-up (96 weeks)
Other outcomes:
Locations:
city: Glendale
country: United States
facility: AKDHC Medical Research Services, LLC.
state: Arizona
city: Chula Vista
country: United States
facility: California Institute of Renal Research - Chula Vista Location
state: California
city: Denver
country: United States
facility: Colorado Kidney Care PC - Dr. Marder
state: Colorado
city: Washington
country: United States
facility: Medical Faculty Associates
state: District of Columbia
city: Augusta
country: United States
facility: Southeastern Clinical Research Institute, LLC
state: Georgia
city: Lawrenceville
country: United States
facility: GA Nephrology Associates
state: Georgia
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Brookview Hills Research Associates, LLC
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Clinical Trials Management Office - Ohio State CTMO Parent
state: Ohio
city: Bethlehem
country: United States
facility: Northeast Clinical Research Center, LLC
state: Pennsylvania
city: Chattanooga
country: United States
facility: Southeast Renal Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Nephrotex Research Group
state: Texas
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center & Children's Hospital
state: Washington
city: Bunkyo-ku
country: Japan
facility: Juntendo University Hospital - Dept of Nephrology/Hypertension
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust - ULTIMATE PARENT
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: