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Efficacy and Safety of Atacicept in IgA Nephropathy

Primary Purpose

IgA Nephropathy

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
Atacicept 25 mg
Atacicept 75 mg
Sponsored by
EMD Serono Research & Development Institute, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for IgA Nephropathy focused on measuring Atacicept, IgA Nephropathy, Berger´s disease, Glomerulonephritis, Proteinuria

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • AKDHC Medical Research Services, LLC.
  • California Institute of Renal Research - Chula Vista Location
  • Colorado Kidney Care PC - Dr. Marder
  • Medical Faculty Associates
  • Southeastern Clinical Research Institute, LLC
  • GA Nephrology Associates
  • Ochsner Clinic Foundation
  • The Johns Hopkins Hospital
  • Massachusetts General Hospital
  • Columbia University Medical Center
  • Brookview Hills Research Associates, LLC
  • Ohio State University Clinical Trials Management Office - Ohio State CTMO Parent
  • Northeast Clinical Research Center, LLC
  • Southeast Renal Research Institute
  • Nephrotex Research Group
  • Providence Sacred Heart Medical Center & Children's Hospital
  • Juntendo University Hospital - Dept of Nephrology/Hypertension
  • University Hospitals of Leicester NHS Trust - ULTIMATE PARENT

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Placebo

Atacicept 25 mg

Atacicept 75 mg

Arm Description

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.
Change From Baseline Levels in Serum Immunoglobulin A (IgA)
The change in serum levels of IgA from baseline was reported.
Change From Baseline Levels in Serum Iimmunoglobulin G (IgG)
The change in serum levels of IgG from baseline was reported.
Change From Baseline Levels in Serum Immunoglobulin M (IgM)
The change in serum levels of IgM from baseline was reported.
Change From Baseline in Serum Galactose Deficient-IgA1 (Gd-IgA1) Levels
The change in serum Gd-IgA1 from baseline was reported.
Change From Baseline in Serum Complement C3 and C4 Levels
The change in serum component C3 and C4 from baseline were reported.
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.
Change From Baseline in Urinary IgG, IgA, and IgM Levels
Urinary IgG, IgA and IgM levels to be measured by Immuno-Electrophoresis.
Percentage of Participants With Positive Anti-Drug Antibody (ADA)
Percentage of participants with positive ADA were reported.
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.
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.
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.

Full Information

First Posted
June 16, 2016
Last Updated
February 4, 2021
Sponsor
EMD Serono Research & Development Institute, Inc.
Collaborators
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT02808429
Brief Title
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

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Terminated
Why Stopped
Study was terminated early as per sponsor decision due to unexpectedly slow enrollment.
Study Start Date
January 31, 2017 (Actual)
Primary Completion Date
February 7, 2020 (Actual)
Study Completion Date
February 7, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
EMD Serono Research & Development Institute, Inc.
Collaborators
Merck KGaA, Darmstadt, Germany

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
IgA Nephropathy
Keywords
Atacicept, IgA Nephropathy, Berger´s disease, Glomerulonephritis, Proteinuria

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Experimental
Arm Title
Atacicept 25 mg
Arm Type
Experimental
Arm Title
Atacicept 75 mg
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants received placebo matched to Atacicept once weekly as subcutaneous (SC) injection during this study up to a maximum of 72.1 weeks.
Intervention Type
Drug
Intervention Name(s)
Atacicept 25 mg
Intervention Description
Participants received 25 milligrams (mg) of Atacicept once weekly as SC injection during this study up to a maximum of 73.6 weeks.
Intervention Type
Drug
Intervention Name(s)
Atacicept 75 mg
Intervention Description
Participants received 75 mg of Atacicept once weekly as SC injection during this study up to a maximum of 74.1 weeks.
Primary Outcome Measure Information:
Title
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
Description
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).
Time Frame
Baseline up to 96 weeks
Secondary Outcome Measure Information:
Title
Serum Atacicept Concentrations
Description
Serum Atacicept Concentrations was to be performed; however; as per changed in planned analysis the outcome measure related to pharmacokinetic parameters was not assessed.
Time Frame
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
Title
Change From Baseline Levels in Serum Immunoglobulin A (IgA)
Description
The change in serum levels of IgA from baseline was reported.
Time Frame
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
Title
Change From Baseline Levels in Serum Iimmunoglobulin G (IgG)
Description
The change in serum levels of IgG from baseline was reported.
Time Frame
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
Title
Change From Baseline Levels in Serum Immunoglobulin M (IgM)
Description
The change in serum levels of IgM from baseline was reported.
Time Frame
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
Title
Change From Baseline in Serum Galactose Deficient-IgA1 (Gd-IgA1) Levels
Description
The change in serum Gd-IgA1 from baseline was reported.
Time Frame
Baseline, Weeks 4, 12, 24, 48, 72, Early Termination (up to Week 72 and at PT FU Weeks 12 and 24
Title
Change From Baseline in Serum Complement C3 and C4 Levels
Description
The change in serum component C3 and C4 from baseline were reported.
Time Frame
Baseline, Week 12, 24, 48, 72, Early Termination (up to Week 72) and at PT FU Weeks 12 and 24
Title
Change From Baseline in Immune Cell Subsets by Flow Cytometry Analysis
Description
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.
Time Frame
Baseline, Weeks 4, 12, 24, 48, 72, Early Termination (up to Week 72) and at PT FU Week 24
Title
Change From Baseline in Urinary IgG, IgA, and IgM Levels
Description
Urinary IgG, IgA and IgM levels to be measured by Immuno-Electrophoresis.
Time Frame
Baseline (Day1), Weeks 24, 48 and Early Termination (up to earlier than Week 72)
Title
Percentage of Participants With Positive Anti-Drug Antibody (ADA)
Description
Percentage of participants with positive ADA were reported.
Time Frame
Baseline up to safety follow-up (96 weeks)
Title
Percentage of Participants With Clinical Significant Abnormalities in Laboratory Assessments
Description
Laboratory investigation included hematology, biochemistry, urinalysis and Urine sediment analysis. Clinical significance was to be decided by the investigator.
Time Frame
Baseline up to safety follow-up (96 weeks)
Title
Percentage of Participants With Clinical Significant Abnormalities in Vital Signs
Description
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.
Time Frame
Baseline up to safety follow-up (96 weeks)
Title
Percentage of Participants With Clinical Significant Abnormalities in 12-Lead Electrocardiograms (ECGs)
Description
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.
Time Frame
Baseline up to safety follow-up (96 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
AKDHC Medical Research Services, LLC.
City
Glendale
State/Province
Arizona
ZIP/Postal Code
85308
Country
United States
Facility Name
California Institute of Renal Research - Chula Vista Location
City
Chula Vista
State/Province
California
ZIP/Postal Code
91910
Country
United States
Facility Name
Colorado Kidney Care PC - Dr. Marder
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Medical Faculty Associates
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20037
Country
United States
Facility Name
Southeastern Clinical Research Institute, LLC
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30909
Country
United States
Facility Name
GA Nephrology Associates
City
Lawrenceville
State/Province
Georgia
ZIP/Postal Code
30046
Country
United States
Facility Name
Ochsner Clinic Foundation
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
The Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Brookview Hills Research Associates, LLC
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
Ohio State University Clinical Trials Management Office - Ohio State CTMO Parent
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Northeast Clinical Research Center, LLC
City
Bethlehem
State/Province
Pennsylvania
ZIP/Postal Code
18017
Country
United States
Facility Name
Southeast Renal Research Institute
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
Nephrotex Research Group
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Providence Sacred Heart Medical Center & Children's Hospital
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
Juntendo University Hospital - Dept of Nephrology/Hypertension
City
Bunkyo-ku
ZIP/Postal Code
113-8431
Country
Japan
Facility Name
University Hospitals of Leicester NHS Trust - ULTIMATE PARENT
City
Leicester
ZIP/Postal Code
LE5 4PW
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing URL
https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html
Links:
URL
http://medical.emdserono.com/en_US/home.html
Description
US Medical Information website, Medical Resources
URL
https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS700461-0035
Description
Trial Awareness and Transparency website

Learn more about this trial

Efficacy and Safety of Atacicept in IgA Nephropathy

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