Efficacy and Safety of Atacicept in IgA Nephropathy

Overview

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.

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

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: February 7, 2020

Interventions

  • 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.
  • 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.
  • 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.

Arms, Groups and Cohorts

  • Experimental: Placebo
  • Experimental: Atacicept 25 mg
  • Experimental: Atacicept 75 mg

Clinical Trial Outcome Measures

Primary 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
    • 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 Measures

  • Serum Atacicept Concentrations
    • 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
    • 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)
    • 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
    • The change in serum levels of IgA from baseline was reported.
  • Change From Baseline Levels in Serum Iimmunoglobulin G (IgG)
    • 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
    • The change in serum levels of IgG from baseline was reported.
  • Change From Baseline Levels in Serum Immunoglobulin M (IgM)
    • 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
    • The change in serum levels of IgM from baseline was reported.
  • Change From Baseline in Serum Galactose Deficient-IgA1 (Gd-IgA1) Levels
    • Time Frame: Baseline, Weeks 4, 12, 24, 48, 72, Early Termination (up to Week 72 and at PT FU Weeks 12 and 24
    • The change in serum Gd-IgA1 from baseline was reported.
  • Change From Baseline in Serum Complement C3 and C4 Levels
    • Time Frame: Baseline, Week 12, 24, 48, 72, Early Termination (up to Week 72) and at PT FU Weeks 12 and 24
    • The change in serum component C3 and C4 from baseline were reported.
  • Change From Baseline in Immune Cell Subsets 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
    • 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
    • Time Frame: Baseline (Day1), Weeks 24, 48 and Early Termination (up to earlier than Week 72)
    • Urinary IgG, IgA and IgM levels to be measured by Immuno-Electrophoresis.
  • Percentage of Participants With Positive Anti-Drug Antibody (ADA)
    • Time Frame: Baseline up to safety follow-up (96 weeks)
    • Percentage of participants with positive ADA were reported.
  • Percentage of Participants With Clinical Significant Abnormalities in Laboratory Assessments
    • Time Frame: Baseline up to safety follow-up (96 weeks)
    • 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
    • Time Frame: Baseline up to safety follow-up (96 weeks)
    • 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)
    • Time Frame: Baseline up to safety follow-up (96 weeks)
    • 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.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • EMD Serono Research & Development Institute, Inc.
  • Collaborator
    • Merck KGaA, Darmstadt, Germany
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Medical Responsible, Study Director, Merck KGaA, Darmstadt, Germany

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