A Cooperative Clinical Study of Abatacept in Multiple Sclerosis

NCT ID: NCT01116427

Last Updated: 2016-09-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2015-02-28

Brief Summary

The ACCLAIM study is testing whether the medication "abatacept" can be of benefit to patients with relapsing-remitting multiple sclerosis (MS). Although abatacept is an investigational medication for MS, it is not a new drug. Abatacept has been approved by the FDA to treat rheumatoid arthritis.

Detailed Description

MS is a chronic autoimmune disease in which blood cells that are supposed to protect the body from infection mistakenly attack the body's own tissue. In MS, the target of this attack is a protein called myelin that coats nerves throughout the body. Damage to this protective layer can lead to loss of neurologic function.

There are a number of treatments available to MS patients. Interferon beta, Copaxone, and other drugs can delay the worsening of the disease in some patients. For other patients, more aggressive treatment with chemotherapy drugs such as cyclophosphamide or azathioprine are needed. These drugs attempt to slow the disease by limiting the activity of the entire immune system. Because of this, they can often have serious side effects.

This study evaluates the efficacy of abatacept in the treatment of relapsing-remitting MS. In the first phase of the study, all participants will receive 8 intravenous treatments over a period of 24 weeks. Then, if a participant remains eligible, they will enter the second phase of the study and will receive another 8 treatments over the following 24 weeks. Two-thirds (2 out of 3) of participants will receive the study drug abatacept in the first phase, and then an inactive form (placebo) of the drug in the second phase. The remaining one-third (1 in 3) will get the placebo first, then the study drug in the second phase if they remain eligible. Therefore, all participants in the ACCLAIM trial will have the opportunity to receive the study drug abatacept if they remain healthy during the study. Participants will be asked to return for a follow-up visit 12 weeks after all treatments have been completed.

Regular appointments scheduled during the trial will be used to monitor participants' health and progress in the study. These appointments will include: physical and neurological exams, blood tests and motor function assessments. A total of 11 magnetic resonance imaging (MRI) procedures are scheduled during the study. The study medication and procedures related to the study will be provided at no expense to the participant.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Abatacept

Receives abatacept during first course of treatment, switching to placebo during extension phase.

Group Type: EXPERIMENTAL

abatacept

Intervention Type: BIOLOGICAL

In core/extension phase: administered IV at weeks 0/28, 2/30, and 4/32, and then every 4 weeks until week 24/52; Dosing: less than 60 kg, 500 mg; 60-100 kg, 750 mg; or greater than 100 kg, 1 gram

Placebo

Intervention Type: DRUG

In core/extension phase: administered IV at weeks 0/28, 2/30, and 4/32, and then every 4 weeks until week 24/52

Placebo, followed by abatacept

Receives a placebo for first course of treatment, switching to abatacept in the extension phase.

Group Type: PLACEBO_COMPARATOR

abatacept

Intervention Type: BIOLOGICAL

In core/extension phase: administered IV at weeks 0/28, 2/30, and 4/32, and then every 4 weeks until week 24/52; Dosing: less than 60 kg, 500 mg; 60-100 kg, 750 mg; or greater than 100 kg, 1 gram

Placebo

Intervention Type: DRUG

In core/extension phase: administered IV at weeks 0/28, 2/30, and 4/32, and then every 4 weeks until week 24/52

Interventions

abatacept

In core/extension phase: administered IV at weeks 0/28, 2/30, and 4/32, and then every 4 weeks until week 24/52; Dosing: less than 60 kg, 500 mg; 60-100 kg, 750 mg; or greater than 100 kg, 1 gram

Intervention Type: BIOLOGICAL

Placebo

In core/extension phase: administered IV at weeks 0/28, 2/30, and 4/32, and then every 4 weeks until week 24/52

Intervention Type: DRUG

Other Intervention Names

Orencia®; CTLA4-Ig; placebo abatacept

Eligibility Criteria

Inclusion Criteria

• Clinically definite Relapsing-remitting Multiple Sclerosis (RRMS) meeting McDonald's criteria
• Expanded Disability Status Scale (EDSS) scores between 0 and 5
• Active disease as defined by at least one of the following criteria:

1. One or more documented clinical exacerbations in the past year prior to visit -2

2. One or more gadolinium (Gd)-enhanced MRI lesions in the past year

• Willingness to forego available MS therapies
• Ability and willingness to provide informed consent and comply with study requirements and procedures

Exclusion Criteria

• Normal brain MRI at week -5 scan
• Females who are pregnant, intending pregnancy, or lactating, and unwilling to undergo pregnancy testing
• Females who are unwilling to use approved methods of contraception for the duration of the study
• Any chronic medical disease, other than MS, that compromises organ function
• Active infection
• Diagnosis of secondary or primary progressive MS
• Previous treatment with cyclophosphamide, mitoxantrone, cladribine, or rituximab at any time
• Previous treatment with abatacept within the last 52 weeks prior to visit -2
• Previous treatment with systemic steroids, interferon, Copaxone, mycophenolate, or other immunosuppressive medications within the last 4 weeks prior to visit -2
• Previous treatment with Natalizumab within the last 26 weeks prior to visit -2
• Previous vaccination with live vaccine, or previous treatment with fingolimod, within the last 8 weeks prior to visit-2
• Diagnosis of malignancy other than basal cell carcinoma or cervical carcinoma in situ
• Claustrophobia or other contraindications to Gd-enhanced MRI
• Positive for human immunodeficiency virus (HIV) serology
• Positive for hepatitis B surface antigen (HBsAg)
• Positive for hepatitis C virus (HCV) serology
• Purified protein derivative (PPD)-tuberculin skin test result greater than 5 mm induration
• Hemoglobin less than 10.5 gm/dL
• Platelets less than 100K/µL
• Absolute lymphocyte count less than 700 cells/μL
• Serum creatinine greater than 1.20 mg/dL
• eGFR (estimated glomerular filtration rate) less than 60 mL/min/1.73 m^2
• IgG anti-cardiolipin antibody greater than 15 GPL U/mL
• Previous participation in another interventional clinical trial within the past 4 weeks prior to visit -2
• Allergy or sensitivity to any component of abatacept
• The presence of any medical condition that the investigator deems incompatible with participation in the trial

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Immune Tolerance Network (ITN)

NETWORK

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Samia Khoury, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

St. Josephs Hospital and Medical Center - Barrow Neurology

Phonix, Arizona, United States

Jordan Research and Education Institute (REDI): Alta Bates Summit Medical Center

Berkeley, California, United States

University of Southern California - Keck School of Medicine

Los Angeles, California, United States

Newport Beach Clinical Research Associates, Inc.

Newport Beach, California, United States

University of California, Davis

Sacramento, California, United States

University of Miami

Miami, Florida, United States

South Suburban Neurology

Flossmoor, Illinois, United States

Norton Neuroscience Institute - Norton Neurology Services MS Center

Louisville, Kentucky, United States

Louisiana State University

Shreveport, Louisiana, United States

University of Maryland

Baltimore, Maryland, United States

Brigham & Women's Hospital

Boston, Massachusetts, United States

University of Minnesota

Minneapolis, Minnesota, United States

Judith Jaffe Multiple Sclerosis Center: Weill Cornell Medical College

New York, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Neurology Specialists, Inc.

Dayton, Ohio, United States

Providence St. Vincent Medical Center

Portland, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

The Neurology Foundation, Inc.

Providence, Rhode Island, United States

Advanced Neurosciences Institute

Franklin, Tennessee, United States

Benaroya Research Institute at Virginia Mason

Seattle, Washington, United States

Ottawa Hospital Research Institute

Ottawa, Ontario, Canada

Countries

United States; Canada

References

Viglietta V, Bourcier K, Buckle GJ, Healy B, Weiner HL, Hafler DA, Egorova S, Guttmann CR, Rusche JR, Khoury SJ. CTLA4Ig treatment in patients with multiple sclerosis: an open-label, phase 1 clinical trial. Neurology. 2008 Sep 16;71(12):917-24. doi: 10.1212/01.wnl.0000325915.00112.61.

Reference Type: BACKGROUND

PMID: 18794494 (View on PubMed)

Khoury SJ, Rochon J, Ding L, Byron M, Ryker K, Tosta P, Gao W, Freedman MS, Arnold DL, Sayre PH, Smilek DE; ACCLAIM Study Group. ACCLAIM: A randomized trial of abatacept (CTLA4-Ig) for relapsing-remitting multiple sclerosis. Mult Scler. 2017 Apr;23(5):686-695. doi: 10.1177/1352458516662727. Epub 2016 Aug 5.

Reference Type: RESULT

PMID: 27481207 (View on PubMed)

Study Documents

Document Type: Study protocol synopsis, -navigator, -schedule of assessments, study schema, and manuscript(s) with overviews, data and reports, participant level data

ACCLAIM ITN035AI is the Study Identifier in the Immune Tolerance Network (ITN) TrialShare Clinical Trials Research Portal

View Document

Related Links

http://www.niaid.nih.gov/Pages/default.aspx

National Institute of Allergy and Infectious Diseases (NIAID)

http://www.immunetolerance.org

Immune Tolerance Network (ITN)

http://www.itntrialshare.org

ITN TrialShare: open public access to study level information

Other Identifiers

DAIT ITN035AI

Identifier Type: -

Identifier Source: org_study_id