Efficacy and Safety Study of Abatacept to Treat Lupus Nephritis

NCT00430677 | Terminated Phase 2 Results DMC

• 1 other identifier: IM101-075
• Study Type: interventional
• Target: 423
• Locations: 18 countries
• Sites: 84

Brief Summary

The purpose of this clinical research study is to learn if addition of abatacept is safe and improves the effectiveness of treatment of patients with active lupus nephritis who are also taking mycophenolate mofetil (MMF) and corticosteroids.

Conditions

Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (1)

• Time to First Confirmed Complete Renal Response (CRR) During the Short-term (Double-blind) Period

  Confirmed at 2 consecutive visits. CRR defined as meeting all of 5 criteria. Renal function (RF): (Glomerular filtration rate \[GFR\] calculated using Modification of Diet in Renal Diseases equation equation) Calculated function abnormal at screening visit - return of renal function to greater than or equal to 90% of function at approximately 6 months prior to onset of the current episode of lupus nephritis. Calculated function normal at screening visit - estimated renal function 90% or greater of level at screening visit. Proteinuria: urinary protein/creatinine ratio \<30 mg/mmol. Hematuria: red blood cell (RBC) count within normal limits of Central Laboratory. Pyuria: White blood cell count (WBC) within normal limits of Central Laboratory. Cylindruria: No RBC or WBC casts reported.

  Day 1 (randomization) to 12 months.

Secondary Outcomes (40)

• Number of Participants With Confirmed Complete Renal Response (CRR) During Short-term Period

  Day 1 to 12 months

• Participants Achieving a Confirmed Complete Renal Response (CRR) at Month 12 During Short-term Period

  At Month 12 from Day 1

• Time to Achieve First Confirmed Renal Improvement (RI) During Short-term Period (as Determined by Kaplan-Meier Methodology)

  Day 1 (randomization) to 12 months.

• Participants Achieving Renal Improvement (RI) or CRR at Month 12 During Short-term Period

  At Month 12 from Day 1

• Number of Months CRR Was Maintained During Short-term Period

  Day 1 (randomization) to 12 Months

Other Outcomes (1)

• Number of Participants Achieving Patient Response (PR) at Month 12 During the Short-term Period

  Month 12

Study Arms (4)

Abatacept 30 mg/kg+Corticosteroids+MMF

EXPERIMENTAL

Short-term Period

Drug: Corticosteroids (prednisone or prednisolone); Drug: Abatacept; Drug: Mycophenolate mofetil (MMF)

Abatacept 10 mg/kg+Corticosteroids+MMF

EXPERIMENTAL

Short-term Period

Drug: Corticosteroids (prednisone or prednisolone); Drug: Abatacept; Drug: Mycophenolate mofetil (MMF)

Placebo+Corticosteroids+MMF

EXPERIMENTAL

Short-term Period

Drug: Corticosteroids (prednisone or prednisolone); Drug: Mycophenolate mofetil (MMF)

Abatacept 10mg/kg

EXPERIMENTAL

Long-term Extension Period

Drug: Abatacept

Interventions

Corticosteroids (prednisone or prednisolone) DRUG

tablets, oral, 0.5-0.8 mg/kg, daily

Abatacept 10 mg/kg+Corticosteroids+MMF; Abatacept 30 mg/kg+Corticosteroids+MMF; Placebo+Corticosteroids+MMF

Abatacept DRUG

intravenous solution, injectable, 30 mg/kg, every 28 days

Also known as: Orencia, BMS-188667

Abatacept 30 mg/kg+Corticosteroids+MMF

Mycophenolate mofetil (MMF) DRUG

tablets, oral, 1.5 to 2 g, daily

Abatacept 10 mg/kg+Corticosteroids+MMF; Abatacept 30 mg/kg+Corticosteroids+MMF; Placebo+Corticosteroids+MMF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 coincident. The 4 criteria need not be present at study entry
• Renal biopsy within 12 months prior to screening visit indicating active proliferative lupus glomerulonephritis (met ISN/RPS Class III or IV classification criteria \[2003\], excluding Class III \[C\], IV-S \[C\] and IV-G \[C\], or the World Health Organization Class III or IV classification criteria \[1982\], excluding Class IIIc, IVd). If the renal biopsy was performed \>3 months but ≤12 months prior to screening visit, at least 1 of the following 3 serologies (performed locally) must have been abnormal prior to screening visit: complement (C3 or C4) level below normal range OR anti-dsDNA \>upper limit of normal range.
• A stable serum creatinine ≤3 mg/dL

You may not qualify if:

• Subjects with a rise in serum creatinine of ≥1 mg/dL within 1 month prior to the screening visit
• Subjects with drug-induced SLE, as opposed to idiopathic SLE
• Subjects with severe, unstable and/or progressive Central nervous system (CNS) lupus
• Subjects with autoimmune disease other than SLE as their main diagnosis (e.g.; Rheumatoid arthritis (RA), Multiple Sclerosis \[MS\])
• Subjects who have received treatment with cyclophosphamide within 3 months of randomization (Day 1).
• Subjects who have received treatment with rituximab \< 6 months prior to the screening visit

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (84)

University Of Alabama At Birmingham

Birmingham, Alabama, 35294, United States

Location

Arizona Arthritis Center

Tucson, Arizona, 85724, United States

Location

Wallace Rheumatic Study Center

Los Angeles, California, 90048, United States

Location

University Of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Boston University School Of Medicine

Boston, Massachusetts, 02118, United States

Location

Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Suny Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

Northshore Lij Health System

Lake Success, New York, 11042, United States

Location

The Feinstein Institute For Medical Research

Manhasset, New York, 11030, United States

Location

Suny Upstate Medical University

Syracuse, New York, 13210, United States

Location

University Of North Carolina At Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Ok Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

Location

Rheumatology Consultants Pllc

Knoxville, Tennessee, 37909, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Local Institution

Capital Federal, Buenos Aires, 1015, Argentina

Location

Local Institution

Ciudad Autonoma de Buenos Aire, Buenos Aires, 1055, Argentina

Location

Local Institution

Córdoba, Córdoba Province, 5016, Argentina

Location

Local Institution

San Miguel de Tucumán, Tucumán Province, 4000, Argentina

Location

Local Institution

Liverpool, New South Wales, 2170, Australia

Location

Local Institution

Clayton, Victoria, 3168, Australia

Location

Local Institution

Heidelberg, Victoria, 3084, Australia

Location

Local Institution

Parkville, Victoria, 3050, Australia

Location

Local Institution

Brussels, 1200, Belgium

Location

Local Institution

Leuven, 3000, Belgium

Location

Local Institution

Goiânia, Goiás, 74110, Brazil

Location

Local Institution

Curitiba, Paraná, 80060, Brazil

Location

Local Institution

Rio de Janeiro, Rio de Janeiro, 20551, Brazil

Location

Local Institution

Porto Alegre, Rio Grande do Sul, 91610, Brazil

Location

Local Institution

São Paulo, São Paulo, 04026, Brazil

Location

Local Institution

Edmonton, Alberta, T6G 2S2, Canada

Location

Local Institution

Winnipeg, Manitoba, R3A 1M4, Canada

Location

Local Institution

Toronto, Ontario, M5T 2S8, Canada

Location

Local Institution

Québec, Quebec, G1R 2J6, Canada

Location

Local Institution

Beijing, Beijing Municipality, 100034, China

Location

Local Institution

Beijing, Beijing Municipality, 100044, China

Location

Local Institution

Beijing, Beijing Municipality, 100730, China

Location

Local Institution

Beijing, Beijing Municipality, 100853, China

Location

Local Institution

Guangzhou, Guangdong, 510080, China

Location

Local Institution

Shanghai, Shanghai Municipality, 200001, China

Location

Local Institution

Shanghai, Shanghai Municipality, 200025, China

Location

Local Institution

Xi’an, Shanxi, 710032, China

Location

Local Institution

Créteil, 94010, France

Location

Local Institution

Paris, 75651, France

Location

Local Institution

Strasbourg, 67098, France

Location

Local Institution

Toulouse, 31403, France

Location

Local Institution

Hong Kong, Hong Kong

Location

Local Institution

Gujarat, Ahmedabad, 380016, India

Location

Local Institution

Secunderabad, Andhra Pradesh, 500003, India

Location

Local Institution

Ahmedabad, Gujarat, 380 007, India

Location

Local Institution

Nadiād, Gujarat, 387001, India

Location

Local Institution

Bangalore, Karnataka, 560 017, India

Location

Local Institution

Bangalore, Karnataka, 560 034, India

Location

Local Institution

Kochi, Kerala, 682026, India

Location

Local Institution

Mumbai, Maharajhsra, 400064, India

Location

Local Institution

Hyderabad, 500082, India

Location

Local Institution

Visakhapatnam, 530002, India

Location

Local Institution

Aguascalientes, Aguascalientes, 20000, Mexico

Location

Local Institution

Guadalajara, Jalisco, 44100, Mexico

Location

Local Institution

Guadalajara, Jalisco, 44690, Mexico

Location

Local Institution

Mexico City, Mexico City, 06726, Mexico

Location

Local Institution

Monterrey, Nuevo León, 64020, Mexico

Location

Local Institution

San Luis Potosí City, San Luis Potosí, 78240, Mexico

Location

Local Institution

Metepec, State of Mexico, 52140, Mexico

Location

Local Institution

Mérida, Yucatán, 97000, Mexico

Location

Local Institution

Bydgoszcz, 85-094, Poland

Location

Local Institution

Gdansk, 80-952, Poland

Location

Local Institution

Wroclaw, 50-417, Poland

Location

Local Institution

Moscow, 115522, Russia

Location

Local Institution

Yaroslaval, 150062, Russia

Location

Local Institution

Yekaterinburg, 620102, Russia

Location

Local Institution

Johannesburg, Gauteng, 2013, South Africa

Location

Local Institution

Observatory, Western Cape, 7925, South Africa

Location

Local Institution

Panorama, Western Cape, 7500, South Africa

Location

Local Institution

Seoul, Sungdong-Gu, 133-792, South Korea

Location

Local Institution

Seoul, 110-744, South Korea

Location

Local Institution

Seoul, 137-040, South Korea

Location

Local Institution

Kaohsiung City, 833, Taiwan

Location

Local Institution

Taichung, 402, Taiwan

Location

Local Institution

Taichung, 407, Taiwan

Location

Local Institution

Taipei, 11217, Taiwan

Location

Local Institution

Taoyuan District, 333, Taiwan

Location

Local Institution

Gaziantep, 27310, Turkey (Türkiye)

Location

Local Institution

Cambridge, Cambridgeshire, CB2 2QQ, United Kingdom

Location

Local Institution

London, Greater London, SE1 7EX, United Kingdom

Location

Related Publications (4)

• Wolf BJ, Spainhour JC, Arthur JM, Janech MG, Petri M, Oates JC. Development of Biomarker Models to Predict Outcomes in Lupus Nephritis. Arthritis Rheumatol. 2016 Aug;68(8):1955-63. doi: 10.1002/art.39623.

  PMID: 26867033 DERIVED

• Furie R, Nicholls K, Cheng TT, Houssiau F, Burgos-Vargas R, Chen SL, Hillson JL, Meadows-Shropshire S, Kinaszczuk M, Merrill JT. Efficacy and safety of abatacept in lupus nephritis: a twelve-month, randomized, double-blind study. Arthritis Rheumatol. 2014 Feb;66(2):379-89. doi: 10.1002/art.38260.

  PMID: 24504810 DERIVED

• Wofsy D, Hillson JL, Diamond B. Comparison of alternative primary outcome measures for use in lupus nephritis clinical trials. Arthritis Rheum. 2013 Jun;65(6):1586-91. doi: 10.1002/art.37940.

  PMID: 23529285 DERIVED

• Wofsy D, Hillson JL, Diamond B. Abatacept for lupus nephritis: alternative definitions of complete response support conflicting conclusions. Arthritis Rheum. 2012 Nov;64(11):3660-5. doi: 10.1002/art.34624.

  PMID: 22806274 DERIVED

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

Adrenal Cortex Hormones; Prednisone; Prednisolone; Abatacept; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols; Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2007
• First Posted: February 2, 2007
• Study Start: June 1, 2007
• Primary Completion: September 1, 2010
• Study Completion: August 1, 2011
• Last Updated: March 20, 2015
• Results First Posted: May 11, 2012

Record last verified: 2015-03

Locations

CN (8); IN (10); TW (5); PL (3); ZA (3); TU (1); KR (3); AR (4); FR (4); BE (2); US (14); GB (2); HK (1); ME (8); RU (3); AU (4); CA (4); BR (5)