Efficacy and Safety of Atacicept in IgA Nephropathy

IgA Nephropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02808429
• Other study ID #: MS700461-0035
• Secondary ID: 2016-002262-31
• Status: Terminated
• Phase: Phase 2
• Start date: January 31, 2017
• Est. completion date: February 7, 2020

Study information

• Verified date: January 2021
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: February 7, 2020
• Est. primary completion date: February 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• IgA Nephropathy
• Kidney Diseases

Intervention

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

Locations

Country	Name	City	State
Japan	Juntendo University Hospital - Dept of Nephrology/Hypertension	Bunkyo-ku
United Kingdom	University Hospitals of Leicester NHS Trust - ULTIMATE PARENT	Leicester
United States	Southeastern Clinical Research Institute, LLC	Augusta	Georgia
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	Northeast Clinical Research Center, LLC	Bethlehem	Pennsylvania
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Southeast Renal Research Institute	Chattanooga	Tennessee
United States	California Institute of Renal Research - Chula Vista Location	Chula Vista	California
United States	Ohio State University Clinical Trials Management Office - Ohio State CTMO Parent	Columbus	Ohio
United States	Nephrotex Research Group	Dallas	Texas
United States	Colorado Kidney Care PC - Dr. Marder	Denver	Colorado
United States	AKDHC Medical Research Services, LLC.	Glendale	Arizona
United States	GA Nephrology Associates	Lawrenceville	Georgia
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Providence Sacred Heart Medical Center & Children's Hospital	Spokane	Washington
United States	Medical Faculty Associates	Washington	District of Columbia
United States	Brookview Hills Research Associates, LLC	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Japan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)

External Links

•   Trial Awareness and Transparency website
•   US Medical Information website, Medical Resources