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

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:

MedlinePlus related topics: Steroids

Drug Information available for: Mycophenolic acid Mycophenolate sodium Mycophenolate mofetil hydrochloride Mycophenolate mofetil

Genetic and Rare Diseases Information Center resources: Lupus Nephritis Glomerulonephritis

U.S. FDA Resources

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.

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):

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.


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 September 23, 2016