Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis - Full Text View

Purpose

The purpose of this study is to evaluate Orencia (abatacept) for treatment of lupus nephritis when used on a background of Cellcept (mycophenolate) and prednisone (corticosteroids)

Condition	Intervention	Phase
Lupus Nephritis	Biological: BMS-188667 Drug: Mycophenolate mofetil Drug: Prednisone Biological: Placebo matching with BMS-188667	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of BMS-188667 (Abatacept) or Placebo on a Background of Mycophenolate Mofetil and Corticosteroids in the Treatment of Subjects With Active Class III or IV Lupus Nephritis

Resource links provided by NLM:

MedlinePlus related topics: Steroids

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

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

Proportion of subjects achieving Complete Response of renal disease following 52 weeks of treatment, where complete response is a composite endpoint based on renal function, proteinuria, urine sediment, and corticosteroid dose [ Time Frame: At Day 365 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of subjects with ranked outcome of complete renal response, partial renal response and no response [ Time Frame: At Day 365 ] [ Designated as safety issue: No ]
Proportion of subjects in complete renal response of lupus glomerulonephritis [ Time Frame: At Day 729 ] [ Designated as safety issue: No ]
Proportion of subjects with ranked outcome of complete renal response, partial renal response and no response [ Time Frame: At Day 729 ] [ Designated as safety issue: No ]
Time to achieving first complete renal response [ Time Frame: At Day 365 ] [ Designated as safety issue: No ]
Time to achieving first partial renal response [ Time Frame: At Day 365 ] [ Designated as safety issue: No ]
Proportion of subjects meeting each of the components of PR and CR of response [ Time Frame: At Day 365 ] [ Designated as safety issue: No ]
Proportion of subjects meeting each of the components of Partial response (PR) and Complete renal response (CR) [Urine protein creatinine ratio (UPCR)< 0.5, UPCR reduced by 50% and meeting target, Estimated Glomerular Filtration Rate (eGFR) normal or no less than 85% of baseline, corticosteroid dose no greater than 10 mg/day prednisone or prednisone equivalent] of response
Mean change from baseline in disease activity as measured by British Isles Lupus Assessment Group (BILAG) 2004 [ Time Frame: Baseline (Day 1) and At Day 365 ] [ Designated as safety issue: No ]
Time to and proportion of subjects with sustained change to lower level of response, ie, CR to PR or No response (NR), PR to NR (sustained response is defined as response present at 2 consecutive visits) [ Time Frame: At Day 365 ] [ Designated as safety issue: No ]
Time to first lupus treatment failure and proportion of subjects in lupus treatment failures overall, and after achievement of CR or PR [ Time Frame: At Day 365 ] [ Designated as safety issue: No ]
Time to first overall treatment failure and proportion of subjects in lupus treatment failure overall, and after achievement of CR or PR [ Time Frame: At Day 365 ] [ Designated as safety issue: No ]
Safety assessments will be based All adverse events (AEs/SAEs), AEs of interest (infections, malignancies, autoimmune disorders, and infusional reactions), Vital signs, Laboratory test abnormalities [ Time Frame: At Day 365 and 729 ] [ Designated as safety issue: Yes ]
- AEs = Adverse Events
- SAEs = Serious Adverse Events
Proportion of subjects with abatacept induced antibody response [ Time Frame: At Day 365 and 729 ] [ Designated as safety issue: No ]

Estimated Enrollment:	400
Study Start Date:	February 2013
Estimated Study Completion Date:	July 2019
Estimated Primary Completion Date:	July 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: BMS-188667 + Mycophenolate mofetil + Prednisone BMS-188667 30 mg/kg injection by intravenous once monthly, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 weeks	Biological: BMS-188667 Other Name: Orencia Drug: Mycophenolate mofetil Other Name: Cellcept Drug: Prednisone
Placebo Comparator: Placebo + Mycophenolate mofetil + Prednisone Placebo matching with BMS-188667 0 mg injection by intravenous once monthly, Mycophenolate mofetil 1.5 g tablet by mouth and Prednisone up to 60 mg tablet by mouth Daily for 104 Weeks	Drug: Mycophenolate mofetil Other Name: Cellcept Drug: Prednisone Biological: Placebo matching with BMS-188667

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Systemic Lupus Erythematosus (SLE) as defined by meeting at least 4 of the 11 classification criteria of the American College of Rheumatology for the classification of Systemic Lupus Erythematosus, either sequentially or coincidentally
Urine protein creatinine ratio (UPCR) ≥ 1.0 at Screening
Biopsy within 12 months prior to screening visit indicating active proliferative lupus glomerulonephritis International Society of Nephrology (ISN)/ Renal Pathology Society (RPS) 2003 classification Class III or IV [excluding Class III (C), IV-S (C) and IV-G (C)] or World Health Organization (WHO) 1982 Classification Class III or IV (excluding IIIc, IVd)
Evidence of active disease within 3 months of Screening, based on at least one of the following:
- Renal Flare
- UPCR > 3 at Screening
- Active urine sediment, defined as at least one of the following:
  - ≥ 5 red blood cells (RBC) per high power field (hpf)
  - ≥ 5 white blood cells (WBC) per hpf
  - Presence of cellular casts
- Biopsy within 3 months prior to screening visit indicating active proliferative lupus glomerulonephritis
Serum creatinine ≤ 3 mg/dL (ie, ≤ 265 micromol/L)

Exclusion Criteria:

Subjects with drug-induced SLE, as opposed to idiopathic SLE
Subjects with autoimmune disease other than SLE as their main diagnosis [eg; Rheumatoid Arthritis (RA), Multiple Sclerosis (MS)]
Current symptoms of severe, progressive, or uncontrolled non-SLE related renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, neurological, or cerebral disease, or other concomitant medical conditions that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in this study
Active Central nervous system (CNS) lupus [British Isles Lupus Assessment Group (BILAG) A or B)] with the exception of fatigue or mild stable cognitive dysfunction [screening Magnetic Resonating Imaging (MRI) or other imaging of the brain is not required to rule-out CNS disease in subjects who have no clinical features suggesting active CNS disease]
Subjects who are diagnosed as end-stage renal disease
Subjects with persistent non-lupus related pyuria or hematuria (eg, hemorrhagic cystitis)
Subjects with a degree of tubulo-interstitial changes that suggests a significant and irreversible decrease in renal function

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01714817

Contacts

Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email:		Clinical.Trials@bms.com
Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time.

Show 62 Study Locations

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

Study Director:

Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trial Information This link exits the ClinicalTrials.gov site

BMS clinical trial educational resource This link exits the ClinicalTrials.gov site

Investigator Inquiry form This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT01714817 History of Changes
Other Study ID Numbers:	IM101-291, 2012-000714-11
Study First Received:	October 24, 2012
Last Updated:	June 17, 2013
Health Authority:	United States: Institutional Review Board United States: Food and Drug Administration Korea: Food and Drug Administration Taiwan: Department of Health Taiwan: National Bureau of Controlled Drugs Russia: Ethics Committee Russia: Ministry of Health of the Russian Federation Russia: FSI Scientific Center of Expertise of Medical Application Japan: Ministry of Health, Labor and Welfare Japan: Pharmaceuticals and Medical Devices Agency Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Brazil: National Health Surveillance Agency Brazil: Ministry of Health Brazil: National Committee of Ethics in Research Chile: Instituto de Salud Publica de Chile Peru: Instituto Nacional de Salud Mexico: Federal Commission for Sanitary Risks Protection Italy: Ministry of Health Italy: National Bioethics Committee Italy: National Institute of Health Italy: National Monitoring Centre for Clinical Trials - Ministry of Health Italy: The Italian Medicines Agency Hong Kong: Department of Health Singapore: Clinical Trials & Epidemiology Research Unit (CTERU) Singapore: Domain Specific Review Boards Singapore: Health Sciences Authority Thailand: Food and Drug Administration Thailand: Ministry of Public Health Australia: Department of Health and Ageing Therapeutic Goods Administration Australia: National Health and Medical Research Council China: Food and Drug Administration Poland: National Institute of Medicines Poland: Ministry of Health Poland: Ministry of Science and Higher Education Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Romania: National Medicines Agency Turkey: Ministry of Health India: Central Drugs Standard Control Organization India: Indian Council of Medical Research India: Ministry of Science and Technology Czech Republic: State Institute for Drug Control Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos

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
Abatacept
Mycophenolic Acid
Prednisone
Immunosuppressive Agents

Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Anti-Inflammatory Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on June 18, 2013