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

December 11, 2007
February 22, 2016
December 2007
April 2009   (final data collection date for primary outcome measure)
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.
The primary outcome is the proportion of subjects with improvement in renal response to treatment. [ Time Frame: The final measurements is at 52 weeks, and there is a total of 24 with follow-up after that ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00573157 on ClinicalTrials.gov Archive Site
  • 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 ]
Proportion of subjects with normalization of renal function; frequency of new lupus flares [ Time Frame: Same as for primary ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
The Efficacy and Safety of Atacicept in Combination With Mycophenolate Mofetil Used to Treat Lupus Nephritis
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.
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.
Not Provided
Interventional
Phase 2
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Lupus Nephritis
  • 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: 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.
  • Experimental: Atacicept Plus Mycophenolate mofetil Plus Corticosteroids
    Interventions:
    • Drug: Atacicept
    • Drug: Mycophenolate mofetil
    • Drug: Corticosteroids
  • Placebo Comparator: Placebo Plus Mycophenolate mofetil Plus Corticosteroids
    Interventions:
    • Drug: Mycophenolate mofetil
    • Drug: Placebo
    • Drug: Corticosteroids
Ginzler EM, Wax S, Rajeswaran A, Copt S, Hillson J, Ramos E, Singer NG. Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial. Arthritis Res Ther. 2012 Feb 7;14(1):R33. doi: 10.1186/ar3738.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
6
April 2009
April 2009   (final data collection date for primary outcome measure)

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.
Both
16 Years and older   (Child, Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Czech Republic,   Malaysia,   Singapore,   Taiwan
 
NCT00573157
28113, 493G01
Yes
Not Provided
Not Provided
EMD Serono
EMD Serono
ZymoGenetics
Study Director: Medical Responsible EMD Serono, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany
EMD Serono
February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP