Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis

This study is currently recruiting participants.
Verified November 2013 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01714817
First received: October 24, 2012
Last updated: November 22, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to evaluate (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:


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 on Days 1,15, 29, and 57, followed by a weight-tiered dose approximating 10mg/kg injection by intravenous every 4 weeks, 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: Abatacept
Drug: Mycophenolate mofetil
Other Name: Cellcept
Drug: Prednisone
Placebo Comparator: Placebo + Mycophenolate mofetil + Prednisone
Placebo matching with BMS-188667 injection by intravenous on Days 1,15, 29, and 57, followed by every 4 weeks, 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

For additional information please contact the BMS Lupus Nephritis Clinical Trial Matching Service at 895-56-LUPUS. Please visit www.BMSStudyConnect.com for more information on clinical trial participation.

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: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

  Show 98 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
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: November 22, 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 April 17, 2014