Abatacept and Cyclophosphamide Combination Therapy for Lupus Nephritis - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	Immune Tolerance Network (ITN)
Information provided by (Responsible Party):	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00774852

Purpose

This study is for people 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 II

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:

MedlinePlus related topics: Lupus

Drug Information available for: Cyclophosphamide Prednisone Azathioprine sodium salt Abatacept Cytotoxic T-lymphocyte antigen 4 Azathioprine

U.S. FDA Resources

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

Primary Outcome Measures:

Proportion of subjects that achieve a complete response (defined as: stabilization or improvement of estimated glomerular filtration rate, urine protein-to-creatinine ratio <0.5, prednisone dose tapered to <=10 mg/day) [ Time Frame: week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of participants who achieve a partial response [ Time Frame: week 24 ] [ Designated as safety issue: No ]
Proportion of participants who achieve a complete response and who have maintained that complete response [ Time Frame: weeks 24 and 52 ] [ Designated as safety issue: No ]
Time to complete or partial response [ Time Frame: 0 ] [ Designated as safety issue: No ]
Lupus disease activity assessed by multiple measures [ Time Frame: various, up to 104 weeks ] [ Designated as safety issue: No ]
Frequency of adverse events [ Time Frame: 0 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	100
Study Start Date:	November 2008
Estimated Study Completion Date:	October 2014
Estimated Primary Completion Date:	January 2013 (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 Revimmune Drug: azathioprine 2 mg/kg/day orally from weeks 12-28; continue until week 52 if only partial response observed at week 24 Other Name: 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 Revimmune Drug: azathioprine 2 mg/kg/day orally from weeks 12-28; continue until week 52 if only partial response observed at week 24 Other Name: 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

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
Revimmune

Drug: azathioprine

2 mg/kg/day orally from weeks 12-28; continue until week 52 if only partial response observed at week 24

Other Name: 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
Revimmune

Drug: azathioprine

2 mg/kg/day orally from weeks 12-28; continue until week 52 if only partial response observed at week 24

Other Name: 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 a kind of kidney inflammation that occurs in patients with systemic lupus erythematosus (SLE). It is caused by the immune system attacking the kidney. It is among the most serious complications of SLE, and 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 the ACCESS trial for lupus nephritis, an experimental medication known as abatacept will be added to the Euro-lupus therapy to find out 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. It 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 at first, 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 subjects will take prednisone tablets daily during the whole 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 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 of ISN/RPS proliferative nephritis, active urinary sediment, urine protein-to-creatinine ratio > 1, low C3)
Positive antinuclear antibody (ANA) test results 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00774852

Show 24 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

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:

ACCESS Trial Information This link exits the ClinicalTrials.gov site

Immune Tolerance Network website This link exits the ClinicalTrials.gov site

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
Last Updated:	November 4, 2011
Health Authority:	United States: Food and Drug Administration

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
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Glomerulonephritis
Kidney Diseases
Urologic Diseases
Azathioprine
Cyclophosphamide
Abatacept
Prednisone
Antimetabolites
Molecular Mechanisms of Pharmacological Action

Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on February 13, 2012