Efficacy and Safety of Atacicept in IgA Nephropathy

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

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.

Study Overview

• Status: Terminated
• Conditions: IgA Nephropathy
• Intervention / Treatment: Drug: Placebo; Drug: Atacicept 25 mg; Drug: Atacicept 75 mg

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Bunkyo-ku, Japan, 113-8431
    • Juntendo University Hospital - Dept of Nephrology/Hypertension
• United Kingdom
  • Leicester, United Kingdom, LE5 4PW
    • University Hospitals of Leicester NHS Trust - ULTIMATE PARENT
• United States
  • Arizona
    • Glendale, Arizona, United States, 85308
      • AKDHC Medical Research Services, LLC.
  • California
    • Chula Vista, California, United States, 91910
      • California Institute of Renal Research - Chula Vista Location
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Kidney Care PC - Dr. Marder
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • Medical Faculty Associates
  • Georgia
    • Augusta, Georgia, United States, 30909
      • Southeastern Clinical Research Institute, LLC
    • Lawrenceville, Georgia, United States, 30046
      • GA Nephrology Associates
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • The Johns Hopkins Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Brookview Hills Research Associates, LLC
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Clinical Trials Management Office - Ohio State CTMO Parent
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Northeast Clinical Research Center, LLC
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Southeast Renal Research Institute
  • Texas
    • Dallas, Texas, United States, 75231
      • Nephrotex Research Group
  • Washington
    • Spokane, Washington, United States, 99204
      • Providence Sacred Heart Medical Center & Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo	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.
Experimental: Atacicept 75 mg	Drug: 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.
Experimental: Atacicept 25 mg	Drug: 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.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborators: Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2017
• Primary Completion (Actual): February 7, 2020
• Study Completion (Actual): February 7, 2020

Study Registration Dates

• First Submitted: June 16, 2016
• First Submitted That Met QC Criteria: June 16, 2016
• First Posted (Estimate): June 21, 2016

Study Record Updates

• Last Update Posted (Actual): February 25, 2021
• Last Update Submitted That Met QC Criteria: February 4, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Proteinuria; IgA Nephropathy; Glomerulonephritis; Atacicept; Berger´s disease
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Kidney Diseases; Glomerulonephritis, IGA
• Other Study ID Numbers: MS700461-0035; 2016-002262-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, EMD Serono will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No