A Cooperative Clinical Study of Abatacept in Multiple Sclerosis - 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:	NCT01116427

Purpose

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

Condition	Intervention	Phase
Multiple Sclerosis, Relapsing-Remitting	Biological: abatacept Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Multiple Sclerosis Nuclear Scans

Drug Information available for: Abatacept

U.S. FDA Resources

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

Primary Outcome Measures:

Number of new inflammatory MRI lesions on monthly scans [ Time Frame: Weeks 8-24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Absolute number of new inflammatory MRI lesions [ Time Frame: each monthly MRI ] [ Designated as safety issue: No ]
lesion volume accumulation on T2-weighted MRI scans [ Time Frame: over 24 weeks ] [ Designated as safety issue: No ]
change in brain parenchymal fraction [ Time Frame: 0-24 weeks ] [ Designated as safety issue: No ]
new inflammatory lesions [ Time Frame: 8-week intervals ] [ Designated as safety issue: No ]
proportion of patients progressing on the EDSS scale by 1 point [ Time Frame: general ] [ Designated as safety issue: No ]
EDSS = Expanded Disability Status Scale -- http://www.nationalmssociety.org/for-professionals/researchers/clinical-study-measures/fss-and-edss/index.aspx
Annualized relapse rate [ Time Frame: annual ] [ Designated as safety issue: No ]
Mean change in MSFC [ Time Frame: over 24 weeks ] [ Designated as safety issue: No ]
MSFC = Multiple Sclerosis Functional Composite -- http://www.nationalmssociety.org/for-professionals/researchers/clinical-study-measures/msfc/index.aspx
adverse events [ Time Frame: all ] [ Designated as safety issue: Yes ]
various laboratory tests [ Time Frame: all ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	123
Study Start Date:	September 2010
Estimated Study Completion Date:	December 2013
Estimated Primary Completion Date:	February 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Study Receives abatacept during first course of treatment, switching to placebo during extension phase.	Biological: 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 Other Names: Orencia CTLA4Ig Drug: 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
Placebo Comparator: Control Receives a placebo for first course of treatment, switching to abatacept in the extension phase.	Biological: 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 Other Names: Orencia CTLA4Ig Drug: 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

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 Cytoxan or Imuran 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.

The ACCLAIM Study is testing a medication called "abatacept." Abatacept works different from most other MS treatments, as it is more specific in the immune cells that it targets. While abatacept is considered experimental for MS, it has been approved by the FDA to treat rheumatoid arthritis.

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 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 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

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Clinically definite RRMS meeting McDonald's criteria
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 in the past year prior to visit -2.
2. One or more 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 the 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 HIV serology.
Positive for HBsAg.
Positive for HCV serology.
PPD greater than 5 mm induration
Hb less than 10.5 gm/dL.
Platelets less than100K/µL.
Absolute lymphocyte count less than 700 cells/μL.
Serum creatinine greater than 1.20 mg/dL
eGFR less than 60 mL/min/1.73 m2
IgG anti-cardiolipin antibody greater than 15GPL U/µL.
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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01116427

Contacts

Contact: Mitzi Dooley

415-353-4426

mdooley@immunetolerance.org

Show 24 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Immune Tolerance Network (ITN)

Investigators

Principal Investigator:

Samia Khoury, MD

Brigham and Women's Hospital

More Information

Additional Information:

Immune Tolerance Network This link exits the ClinicalTrials.gov site

Study website This link exits the ClinicalTrials.gov site

National Institute of Allergy and Infectious Diseases (NIAID) This link exits the ClinicalTrials.gov site

Publications:

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.

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT01116427 History of Changes
Other Study ID Numbers:	DAIT ITN035AI
Study First Received:	May 3, 2010
Last Updated:	January 13, 2012
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board; United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

MS
multiple sclerosis
relapsing-remitting multiple sclerosis
RR-MS
relapsing remitting MS

Additional relevant MeSH terms:

Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases

Pathologic Processes
Abatacept
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012