The Efficacy and Safety of Atacicept in Combination With Mycophenolate Mofetil Used to Treat Lupus Nephritis

This study has been terminated.
(The study was terminated due to unanticipated safety issues)
Sponsor:
Collaborator:
ZymoGenetics
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT00573157
First received: December 11, 2007
Last updated: February 22, 2016
Last verified: February 2016
  Purpose
The purpose of this study is to learn whether atacicept treatment leads to improvement in kidney function in subjects with active lupus nephritis in combination with mycophenolate mofetil (MMF) and corticosteroids. The study was sponsored by Merck Serono International; operational oversight was provided by ZymoGenetics.

Condition Intervention Phase
Lupus Nephritis
Drug: Atacicept
Drug: Mycophenolate mofetil
Drug: Placebo
Drug: Corticosteroids
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2/3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Atacicept in Subjects With Lupus Nephritis in Combination With Mycophenolate Mofetil Therapy.

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • Percentage of Participants With Confirmed Complete Renal Response (CRR), Partial Response, and Non-response [ Time Frame: At Week 52 ] [ Designated as safety issue: No ]
    Complete renal response (CRR): from baseline, a return to within 10% of normal for renal function (assessed by calculated glomerular filtration rate [GFR]), improvement in proteinuria (urine protein/creatinine ratio <0.5) & resolution of hematuria. Partial response (PR): from baseline, a <= 10% worsening in renal function ( by calculated GFR); 50% improvement in proteinuria (assessed by urine protein/creatinine ratio) & resolution of hematuria, Non-response (NR): Neither criteria for CR or PR was met. Subjects were also deemed NR if they had treatment failure, regardless of CR or PR status. Subjects cannot be treatment failures. A response of CRR was confirmed if the Week 52 value is CRRand if the Week 48 value is CRR and at least 4 weeks apart from Week 52 /if the Week 48 value was missing/ less than 4 weeks from Week 52, then the Week 56 response must be CRR - if the Week 52 value was missing, then Week 48 and Week 56 must be CRR.


Secondary Outcome Measures:
  • Percentage of Participants With Normalization of Renal Function [ Time Frame: At Week 52 ] [ Designated as safety issue: No ]
  • Number of Participants With New Lupus Flares [ Time Frame: At Week 52 ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: December 2007
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atacicept Plus Mycophenolate mofetil Plus Corticosteroids Drug: Atacicept
Atacicept will be administered at a dose of 150 milligram (mg) subcutaneously (SC) twice weekly for 4 weeks followed by maintenance dose of 150 mg SC once weekly for 48 weeks.
Drug: Mycophenolate mofetil
MMF will be administered orally with a starting dose of 500 mg twice daily for 1 week, will be increased to 1000 mg twice daily for 1 week, then it will be adjusted to 1500 mg or lower twice daily as per investigator's discretion.
Drug: Corticosteroids
High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever is less will be administered for 4 Weeks and will be tapered to 7.5 to 10 mg/day up to Week 12.
Placebo Comparator: Placebo Plus Mycophenolate mofetil Plus Corticosteroids Drug: Mycophenolate mofetil
MMF will be administered orally with a starting dose of 500 mg twice daily for 1 week, will be increased to 1000 mg twice daily for 1 week, then it will be adjusted to 1500 mg or lower twice daily as per investigator's discretion.
Drug: Placebo
Placebo will be administered at a dose of 150 mg SC twice weekly for 4 weeks followed by 150 mg SC once weekly for 48 weeks.
Drug: Corticosteroids
High dose CS of 0.8 mg per kilogram per day or maximum of 60 mg per day prednisone or prednisone equivalent, whichever is less will be administered for 4 Weeks and will be tapered to 7.5 to 10 mg/day up to Week 12.

  Eligibility

Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of systemic lupus erythematosus (SLE) satisfying at least 4 out of the 11 American College of Rheumatology (ACR) criteria (Appendix B)
  • Renal biopsy performed consistent with active International Society of Nephrology/Renal Pathology Society (ISN/PRS) class III or IV lupus nephritis

Exclusion Criteria:

  • Estimated glomerular filtration rate (GFR) less than or equal to (<=) 30 milliliter per minute (mL/min) per 1.73 square meter (m^2)
  • Active central nervous system SLE deemed to be severe or progressive and/or associated with significant cognitive impairment
  • Any treatment with MMF, azathioprine, or cyclophosphamide within the last 6 months, or known hypersensitivity to MMF or atacicept.
  • Any prior treatment with abatacept, rituximab, belimumab, or other B cell modulating agents.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00573157

Locations
United States, Louisiana
Tulane University Hospital and Clinic Department of Internal Medicine
New Orleans,, Louisiana, United States
Northwest Louisiana Nephrology Research
Shreveport, Louisiana, United States, 71101
United States, Michigan
Wayne State University Lupus Database Departments of Internal Medicine and Obstetrics & Gynecology Division of Rheumatology Wayne State University School of Medicine
Detroit, Michigan, United States
United States, New York
The Feinstein Institute for Medical Research
Manhasset, New York, United States, 11030
Seligman Center for Advanced Therapeutics
New York, New York, United States, 10003
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27109
United States, Ohio
Rheumatology Clinical Research Unit, Division of Rheumatology University Hospitals Case Medical Center
Beachwood, Ohio, United States, 44122
University of Cincinnati College of Medicine
Cincinnati, Ohio, United States, 45267
The Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Southwest Rheumatology and Research Group, LLC
Middleburg Heights, Ohio, United States, 44130
United States, South Carolina
1711 St. Julian Place
Columbia, South Carolina, United States, 29204
ACME Research, LLC
Orangeburg, South Carolina, United States, 29118
Czech Republic
Institute of Rheumatology
Prague, 128 50, Czech Republic
Malaysia
Hospital Sultanah Bahiyah
Kedah, Malaysia
Hospital University Kebangsaan Malaysia
Kuala Lumpur, Malaysia
University of Malaya Medical Centre
Kuala Lumpur, Malaysia
Hospital Pulau Pinang
Pulau Pinang, Malaysia
Singapore
Changi General Hospital
Singapore, Singapore
Singapore General Hospital
Singapore, Singapore
Taiwan
Kaohsiung Veterans General Hospital
Kaohsiung, Taiwan
Sponsors and Collaborators
EMD Serono
ZymoGenetics
Investigators
Study Director: Medical Responsible EMD Serono, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00573157     History of Changes
Other Study ID Numbers: 28113  493G01 
Study First Received: December 11, 2007
Results First Received: February 22, 2016
Last Updated: February 22, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by EMD Serono:
nephritis
atacicept

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

ClinicalTrials.gov processed this record on July 21, 2016