Atacicept in Lupus Nephritis Patients Taking Stable Regimen of Mycophenolate Mofetil

This study has been terminated.
(Please see Purpose Statement below)
Sponsor:
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT01369628
First received: June 7, 2011
Last updated: October 21, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Lupus Nephritis
Drug: Atacicept
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • The nature (preferred terms) and incidence of AEs [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 36 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 36 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 36 weeks ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 1
Study Start Date: June 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1

1 arm with the 3 following dose regimens:

  1. Regimen 1: Atacicept 25 mg weekly for 12 weeks
  2. Regimen 2: Atacicept 75 mg weekly for 12 weeks
  3. Regimen 3: Atacicept 150 mg weekly for 12 weeks
Drug: Atacicept
  1. Regimen 1: Atacicept 25 mg weekly for 12 weeks
  2. Regimen 2: Atacicept 75 mg weekly for 12 weeks
  3. Regimen 3: Atacicept 150 mg weekly for 12 weeks

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01369628

Locations
United States, Massachusetts
EMD Serono Inc., One Technology Place
Rockland, Massachusetts, United States, 02370
Sponsors and Collaborators
EMD Serono
  More Information

Additional Information:
No publications provided

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT01369628     History of Changes
Other Study ID Numbers: EMR 700461_014
Study First Received: June 7, 2011
Last Updated: October 21, 2013
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: AEMPS

Keywords provided by EMD Serono:
Open label
Dose Escalating
Phase Ib

Additional relevant MeSH terms:
Lupus Nephritis
Nephritis
Glomerulonephritis
Kidney Diseases
Urologic Diseases
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Mycophenolate mofetil
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 14, 2014