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Abatacept and Cyclophosphamide Combination Therapy for Lupus Nephritis (ACCESS)

This study has been completed.
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00774852
First received: October 16, 2008
Last updated: October 7, 2014
Last verified: October 2014
  Purpose

This study is for individuals with lupus who have developed complications in their kidneys, or lupus nephritis. The study will determine whether adding the experimental medication abatacept to standard cyclophosphamide therapy is more effective in improving lupus nephritis than standard cyclophosphamide therapy by itself.


Condition Intervention Phase
Lupus Nephritis
Lupus Erythematosus, Systemic
Drug: abatacept
Drug: cyclophosphamide
Drug: azathioprine
Drug: prednisone
Drug: abatacept placebo
Drug: azathioprine placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Controlled, Phase II Multicenter Trial of CTLA4Ig (Abatacept) Plus Cyclophosphamide vs Cyclophosphamide Alone in the Treatment of Lupus Nephritis

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Number of Participants With Complete Response [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Complete response definition: a serum creatinine <= 1.2 mg/dL or <=125% of the higher value at either screening or baseline visit, protein-to-creatinine ratio <0.5, and prednisone dose tapered to <=10 mg/day or prednisone dosing allowances in protocol. Participants had to meet all of the referenced criteria to be considered a complete responder (CR). Participants who discontinued treatment and/or terminated from the study in the first 24 weeks were defined as CR failures for all subsequent visits. CRs are those who successfully responded to treatment and have minimal activity of their lupus nephritis


Secondary Outcome Measures:
  • Number of Participants With Partial Response [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Outcome measure description: Partial response definition: a serum creatinine <= 1.2 mg/dL or <= to 125% of the higher value at either screening or baseline visit, and improvement (reduction) >= to 50% in the urine protein to creatinine ratio at either screening or baseline visit, and prednisone dose has been tapered to 10 mg/day or according to protocol dosing allowances in protocol. Participants who discontinued treatment and/or terminated from the study in the first 24 weeks were defined as complete response failures for all subsequent visits. Partial responders are those who showed some response to treatment and low activity of their lupus nephritis.


Enrollment: 137
Study Start Date: November 2008
Study Completion Date: June 2014
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Abatacept plus Euro-lupus regimen
Drug: abatacept
Intravenous infusion (500-1000 mg, dep on weight) at weeks 0, 2, and 4, then every 4 weeks until week 24; continue to week 48 only if partial response at 24 weeks
Other Names:
  • CTLA4Ig
  • Orencia
Drug: cyclophosphamide
500 mg intravenous infusion every 2 weeks for 12 weeks
Other Names:
  • Cytoxan
  • Neosar
Drug: azathioprine
2 mg/kg/day orally from weeks 12-28; continue until week 52 if only partial response observed at week 24
Other Names:
  • Imuran
  • Azasan
Drug: prednisone
60 mg/day for 2 weeks, then taper to 10 mg/day by 12 weeks, then continue on stable dose
Other Name: Sterapred
Drug: azathioprine placebo
Oral capsule, daily from weeks 28 to 52, only if complete response observed at week 24
Placebo Comparator: Control
Abatacept placebo plus Euro-lupus regimen
Drug: cyclophosphamide
500 mg intravenous infusion every 2 weeks for 12 weeks
Other Names:
  • Cytoxan
  • Neosar
Drug: azathioprine
2 mg/kg/day orally from weeks 12-28; continue until week 52 if only partial response observed at week 24
Other Names:
  • Imuran
  • Azasan
Drug: prednisone
60 mg/day for 2 weeks, then taper to 10 mg/day by 12 weeks, then continue on stable dose
Other Name: Sterapred
Drug: abatacept placebo
Intravenous infusion at weeks 0, 2, and 4, then every 4 weeks until week 24; continue to week 48 only if partial response at 24 weeks

Detailed Description:

Lupus nephritis is an inflammation of the kidney that occurs in patients with systemic lupus erythematosus (SLE). It is caused by the immune system attacking the kidney and is among the most serious complications of SLE: left untreated it can cause long term damage to the kidneys or, in some cases, result in kidney failure.

One of the more common treatments for lupus nephritis is the "Euro-lupus" therapy. In this therapy, patients receive three different drugs - cyclophosphamide, azathioprine and prednisone - over the course of several months. However, some patients do not respond to this therapy and many only show some improvement.

In this ACCESS trial for lupus nephritis, an experimental medication known as abatacept will be added to the Euro-lupus therapy to assess if it works better than Euro-lupus therapy alone. Abatacept is a man-made protein that suppresses parts of the immune system that can cause autoimmune disease. While abatacept is experimental for lupus, it has been approved by the FDA to treat rheumatoid arthritis. Abatacept is also being studied for use in other autoimmune diseases, like multiple sclerosis and type 1 diabetes.

Participants in the ACCESS trial for lupus nephritis will receive bi-weekly intravenous infusions of cyclophosphamide for 3 months, then will take azathioprine tablets daily for at least 3 months more. Abatacept or a placebo will be administered every 2 weeks initially, then every 4 weeks for at least the first 6 months. Treatment of abatacept or placebo and azathioprine may continue for the remainder of the year. All participants will take prednisone tablets daily during the entire study.

Because the ACCESS trial is a randomized, controlled study, each participant has a 50-50 chance (like flipping a coin) of receiving abatacept. Others will receive an inactive, placebo form of the drug. Note however, that all participants will receive the Euro-lupus therapy. As a blinded (masked) study, neither participants nor study physicians will know to which group a person has been assigned.

All participants will undergo regular physical examinations, medical history and various blood and urine tests. Many of these tests will be repeated throughout the study. Participants will be asked to attend 18 study visits in the first year, and one study visit at the end of the second year.

The study will reimburse participants for certain expenses incurred as part of the study.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of systemic lupus erythematosus (SLE) by American College of Rheumatology (ACR) criteria
  • Active lupus nephritis (defined by: kidney biopsy documentation within the last 12 months using International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification- proliferative nephritis, active urinary sediment, urine protein-to-creatinine ratio > 1, low complement C3)
  • Positive antinuclear antibody (ANA) test result at time of study entry

Exclusion Criteria:

  • End stage renal disease
  • Use of cyclophosphamide in the past year
  • Neutropenia, thrombocytopenia, moderately severe anemia
  • Active infection, including HIV, hepatitis B or C
  • History of cancer, except carcinoma in situ and treated basal and squamous cell carcinomas
  • Pregnant or breastfeeding
  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: NCT00774852

  Show 23 Study Locations
Sponsors and Collaborators
Immune Tolerance Network (ITN)
Investigators
Principal Investigator: David Wofsy, MD University of California, San Francisco
Principal Investigator: Betty Diamond, MD Feinstein Institute
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00774852     History of Changes
Other Study ID Numbers: DAIT ITN034AI
Study First Received: October 16, 2008
Results First Received: August 18, 2014
Last Updated: October 7, 2014
Health Authority: United States: Food and Drug Administration
Mexico: Federal Commission for Sanitary Risks Protection

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
lupus
systemic lupus erythematosus
lupus nephritis
SLE
abatacept
CTLA4
CTLA4Ig
glomerulonephritis

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Lupus Nephritis
Nephritis
Autoimmune Diseases
Connective Tissue Diseases
Glomerulonephritis
Immune System Diseases
Kidney Diseases
Urologic Diseases
Abatacept
Azathioprine
Cyclophosphamide
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014