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Atacicept in Lupus Nephritis Patients Taking Stable Regimen of Mycophenolate Mofetil

Primary Purpose

Lupus Nephritis

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Atacicept
Sponsored by
EMD Serono
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lupus Nephritis focused on measuring Open label, Dose Escalating, Phase Ib

Eligibility Criteria

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

Inclusion Criteria:

  • Male or female subjects, ≥ 18 years of age, who provide written informed consent
  • Subjects must have a diagnosis of SLE satisfying ≥ 4 of 11 ACR criteria, and must have had a renal biopsy during screening or within the previous 18 months demonstrating class III (A or A/C), IV (A or A/C), V, or concomitant III/V or IV/V LN as defined by the International Society of Nephrology/Renal Pathology Society (ISN/RPS).
  • Subjects must have a urine protein: creatinine ratio ≥ 2 mg/mg (≥ 226.2 mg/mmol), and either a positive test for antinuclear antibody (ANA) (HEp-2 ANA ≥ 1:80) and/or anti-double stranded deoxyribonucleic acid (dsDNA) (≥ 30 IU/mL) at screening.
  • Subjects must have started induction therapy for LN at least 5 months prior to Trial Day 1, be considered to have received continuous treatment for LN during the 5 months prior to Trial Day 1, and have received a stable dose of MMF ≥ 1 g/day, with or without corticosteroids, for at least 8 weeks prior to Trial Day 1.

Exclusion Criteria:

  • Recent changes in immunosuppressant, ACD inhibitors for ARBs
  • Use of azathioprine, cyclosporine, tacrolimus, or cyclophosphamide or other biologics within 8 weeks prior to Trial Day 1.
  • Serum IgG < 6 g/L
  • Estimated Glomerular Filtration Rate (GFR) ≤ 30 mL/min per 1.73 m2
  • History of Demyelinating Disease
  • Significant Hematuria and/or Proteinuria due to a reason(s) other than LN. Evaluation should be done according to the local standard of care
  • Breast feed or pregnancy
  • Legal Incapacity or limited legal capacity

Sites / Locations

  • EMD Serono Inc., One Technology Place

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm 1

Arm Description

1 arm with the 3 following dose regimens: Regimen 1: Atacicept 25 mg weekly for 12 weeks Regimen 2: Atacicept 75 mg weekly for 12 weeks Regimen 3: Atacicept 150 mg weekly for 12 weeks

Outcomes

Primary Outcome Measures

The nature (preferred terms) and incidence of AEs
Frequency tables summarizing the observed number of AEs by System Organ Class (SOC) and preferred term will be presented per regimen.
Proportion of subjects fulfilling criteria for an Atacicept dose modification due to an IgG decrease
Percentages of subjects fulfilling the criteria (prespecified in the protocol) for an atacicept dose modification due to a decrease in IgG will be presented.
The frequency and severity of laboratory abnormalities
The incidence of subjects given each atacicept regimen who have shifts from Baseline in serum creatinine, serum albumin, urinary protein, or Hematology test (counts of white blood cells, neutrophils, lymphocytes, platelets) of at least 2 grades will be presented. Grading will be classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 toxicity grading, using the worst grade post-baseline during the 12-week treatment period.

Secondary Outcome Measures

The nature (preferred terms) and incidence of AEs
Frequency tables summarizing the observed number of AEs by System Organ Class (SOC) and preferred term will be presented per regimen.
Proportion of subjects fulfilling criteria for an Atacicept dose modification due to an IgG decrease
Percentages of subjects fulfilling the criteria (prespecified in the protocol) for an atacicept dose modification due to a decrease in IgG will be presented.
The frequency and severity of laboratory abnormalities
The incidence of subjects given each atacicept regimen who have shifts from Baseline in serum creatinine, serum albumin, urinary protein, or Hematology test (counts of white blood cells, neutrophils, lymphocytes, platelets) of at least 2 grades will be presented. Grading will be classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 toxicity grading, using the worst grade post-baseline during the 12-week treatment period.

Full Information

First Posted
June 7, 2011
Last Updated
October 21, 2013
Sponsor
EMD Serono
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1. Study Identification

Unique Protocol Identification Number
NCT01369628
Brief Title
Atacicept in Lupus Nephritis Patients Taking Stable Regimen of Mycophenolate Mofetil
Official Title
A Phase Ib, Multicenter, Open Label, Dose-Escalating, Repeat-Dose Trial to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Atacicept When Administered to Subjects With Lupus Nephritis on a Stable Regimen of Mycophenolate Mofetil (MMF) With or Without Corticosteroids
Study Type
Interventional

2. Study Status

Record Verification Date
October 2013
Overall Recruitment Status
Terminated
Why Stopped
Please see Purpose Statement below
Study Start Date
June 2011 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
EMD Serono

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The sponsor electively terminated the study because the risk mitigation measures, deemed necessary after an unforeseen safety event, could not be effectively implemented within this protocol while maintaining study timelines within a reasonable time frame.
Detailed Description
This study will evaluate atacicept's effects in subjects who have lupus nephritis, at least 2 g/day of protein in the urine, and are already taking mycophenolate mofetil. The evaluations will include the concentrations of atacicept in the blood, the effects of atacicept on immunoglobulins (antibodies), and any side effects. The first subjects will be given a low dose. Following periodic reviews of the trial data, subsequent subjects are planned to receive one of 2 progressively higher doses of atacicept.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lupus Nephritis
Keywords
Open label, Dose Escalating, Phase Ib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
1 arm with the 3 following dose regimens: Regimen 1: Atacicept 25 mg weekly for 12 weeks Regimen 2: Atacicept 75 mg weekly for 12 weeks Regimen 3: Atacicept 150 mg weekly for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Atacicept
Intervention Description
Regimen 1: Atacicept 25 mg weekly for 12 weeks Regimen 2: Atacicept 75 mg weekly for 12 weeks Regimen 3: Atacicept 150 mg weekly for 12 weeks
Primary Outcome Measure Information:
Title
The nature (preferred terms) and incidence of AEs
Description
Frequency tables summarizing the observed number of AEs by System Organ Class (SOC) and preferred term will be presented per regimen.
Time Frame
12 weeks
Title
Proportion of subjects fulfilling criteria for an Atacicept dose modification due to an IgG decrease
Description
Percentages of subjects fulfilling the criteria (prespecified in the protocol) for an atacicept dose modification due to a decrease in IgG will be presented.
Time Frame
12 weeks
Title
The frequency and severity of laboratory abnormalities
Description
The incidence of subjects given each atacicept regimen who have shifts from Baseline in serum creatinine, serum albumin, urinary protein, or Hematology test (counts of white blood cells, neutrophils, lymphocytes, platelets) of at least 2 grades will be presented. Grading will be classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 toxicity grading, using the worst grade post-baseline during the 12-week treatment period.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
The nature (preferred terms) and incidence of AEs
Description
Frequency tables summarizing the observed number of AEs by System Organ Class (SOC) and preferred term will be presented per regimen.
Time Frame
36 weeks
Title
Proportion of subjects fulfilling criteria for an Atacicept dose modification due to an IgG decrease
Description
Percentages of subjects fulfilling the criteria (prespecified in the protocol) for an atacicept dose modification due to a decrease in IgG will be presented.
Time Frame
36 weeks
Title
The frequency and severity of laboratory abnormalities
Description
The incidence of subjects given each atacicept regimen who have shifts from Baseline in serum creatinine, serum albumin, urinary protein, or Hematology test (counts of white blood cells, neutrophils, lymphocytes, platelets) of at least 2 grades will be presented. Grading will be classified according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 toxicity grading, using the worst grade post-baseline during the 12-week treatment period.
Time Frame
36 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female subjects, ≥ 18 years of age, who provide written informed consent Subjects must have a diagnosis of SLE satisfying ≥ 4 of 11 ACR criteria, and must have had a renal biopsy during screening or within the previous 18 months demonstrating class III (A or A/C), IV (A or A/C), V, or concomitant III/V or IV/V LN as defined by the International Society of Nephrology/Renal Pathology Society (ISN/RPS). Subjects must have a urine protein: creatinine ratio ≥ 2 mg/mg (≥ 226.2 mg/mmol), and either a positive test for antinuclear antibody (ANA) (HEp-2 ANA ≥ 1:80) and/or anti-double stranded deoxyribonucleic acid (dsDNA) (≥ 30 IU/mL) at screening. Subjects must have started induction therapy for LN at least 5 months prior to Trial Day 1, be considered to have received continuous treatment for LN during the 5 months prior to Trial Day 1, and have received a stable dose of MMF ≥ 1 g/day, with or without corticosteroids, for at least 8 weeks prior to Trial Day 1. Exclusion Criteria: Recent changes in immunosuppressant, ACD inhibitors for ARBs Use of azathioprine, cyclosporine, tacrolimus, or cyclophosphamide or other biologics within 8 weeks prior to Trial Day 1. Serum IgG < 6 g/L Estimated Glomerular Filtration Rate (GFR) ≤ 30 mL/min per 1.73 m2 History of Demyelinating Disease Significant Hematuria and/or Proteinuria due to a reason(s) other than LN. Evaluation should be done according to the local standard of care Breast feed or pregnancy Legal Incapacity or limited legal capacity
Facility Information:
Facility Name
EMD Serono Inc., One Technology Place
City
Rockland
State/Province
Massachusetts
ZIP/Postal Code
02370
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/20302641
Description
Related Info
URL
http://www.ncbi.nlm.nih.gov/pubmed/19743503
Description
Related Info
URL
http://www.ncbi.nlm.nih.gov/pubmed/19395457
Description
Related Info
URL
http://www.ncbi.nlm.nih.gov/pubmed/18050206
Description
Related Info
URL
http://www.ncbi.nlm.nih.gov/pubmed/10801128
Description
Related Info

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Atacicept in Lupus Nephritis Patients Taking Stable Regimen of Mycophenolate Mofetil

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