Clinical trial NCT01116427: A Cooperative Clinical Study of Abatacept in Multiple Sclerosis
Official title: A Phase II, Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Study to Evaluate the Safety and Efficacy of Abatacept in Adults With Relapsing-remitting Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Sclerosis, Relapsing-Remitting
Keywords: MS
multiple sclerosis
relapsing-remitting multiple sclerosis
RRMS
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Immune Tolerance Network (ITN)
First posted: 2010-05-05
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Mean Number of New Inflammatory MRI Lesions Per Monthly Scans
timeFrame: Weeks 8-24
Secondary outcomes:
measure: Absolute Number of New Inflammatory MRI Lesions on Monthly Scans
timeFrame: Weeks 4-24
measure: Lesion Volume Accumulation on T2-weighted MRI Scans Over 24 Weeks
timeFrame: Week -1 to Week 24
measure: Percent Brain Volume Change
timeFrame: Week -1 to Week 24
measure: Mean Number of New Inflammatory Lesions in 8-week Intervals
timeFrame: Week 8 to Week 24
measure: Number of Participants Progressing on the EDSS Scale by at Least 1 Point
timeFrame: Week -1 to Week 24
measure: Annualized Relapse Rate
timeFrame: Week -1 to Week 24
measure: Mean Change in the MSFC Over 24 Weeks of Treatment
timeFrame: Week -1 to Week 24
measure: Mean Number of New Inflammatory MRI Lesions Per Scan During the Extension Phase
timeFrame: Weeks 36 and 52
measure: Lesion Volume Accumulation on T2-Weighted MRI Scans Between 24 Weeks and 52 Weeks
timeFrame: Week 24 to Week 52
measure: Percent Brain Volume Change Between 24 Weeks and 52 Weeks
timeFrame: Week 24 to Week 52
measure: Number of Participants Progressing on the EDSS Scale by at Least 1 Point
timeFrame: Week 24 to Week 64
measure: Annualized Relapse in Extension Phase
timeFrame: Week 24 to Week 64
measure: Mean Change in the MSFC in Extension Phase
timeFrame: Week 24 to Week 52
Other outcomes:
Locations:
city: Phonix
country: United States
facility: St. Josephs Hospital and Medical Center - Barrow Neurology
state: Arizona
city: Berkeley
country: United States
facility: Jordan Research and Education Institute (REDI): Alta Bates Summit Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California - Keck School of Medicine
state: California
city: Newport Beach
country: United States
facility: Newport Beach Clinical Research Associates, Inc.
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Flossmoor
country: United States
facility: South Suburban Neurology
state: Illinois
city: Louisville
country: United States
facility: Norton Neuroscience Institute - Norton Neurology Services MS Center
state: Kentucky
city: Shreveport
country: United States
facility: Louisiana State University
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: Judith Jaffe Multiple Sclerosis Center: Weill Cornell Medical College
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Dayton
country: United States
facility: Neurology Specialists, Inc.
state: Ohio
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: The Neurology Foundation, Inc.
state: Rhode Island
city: Franklin
country: United States
facility: Advanced Neurosciences Institute
state: Tennessee
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason
state: Washington
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
Study officials:
affiliation: Brigham and Women's Hospital
name: Samia Khoury, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.