- Phoenix, Arizona, United States, 85013
- Tucson, Arizona, United States, 85741
- Fullerton, California, United States, 92835
- Denver, Colorado, United States, 80220
- Naples, Florida, United States, 34102
- Plantation, Florida, United States, 33324
- Sarasota, Florida, United States, 34239
- Northbrook, Illinois, United States, 60062
- Indianapolis, Indiana, United States, 46202
- Kansas City, Kansas, United States, 66160
- Lexington, Kentucky, United States, 40513
- Biddeford, Maine, United States, 04005
- Farmington Hills, Michigan, United States, 48334
- Toms River, New Jersey, United States, 08755
- Schenectady, New York, United States, 12308
- Charlotte, North Carolina, United States, 28207
- Raleigh, North Carolina, United States, 27607
- Akron, Ohio, United States, 44320
- Green, Ohio, United States, 44685
- Greensburg, Pennsylvania, United States, 15601
- Greenville, South Carolina, United States, 29615
- Franklin, Tennessee, United States, 37064
- Memphis, Tennessee, United States, 38120
- Lubbock, Texas, United States, 79410
- Round Rock, Texas, United States, 78681
- Newport News, Virginia, United States, 23601
- Roanoke, Virginia, United States, 24018
- Sofia, Bulgaria, 1407
- Brno, Czech Republic, 62500
- Pardubice, Czech Republic, 500 05
- Prague, Czech Republic, 140 59
- Caen, France, 14033
- Montpellier, France, 34295
- Nimes, France, 30900
- Strasbourg, France, 67091
- Berlin, Germany, 13156
- Ulm, Germany, 89075
- Budapest, Hungary, 1095
- Gyor, Hungary, 9023
- Gyula, Hungary, 5700
- Tel Hashomer, Israel, 52621
- Gdansk, Poland, 80-952
- Gliwice, Poland, 44-100
- Grodzisk Mazowiecki, Poland, 05-825
- Krakow-Nowa Huta, Poland, PL-31-826
- Lodz, Poland, 90-549
- Lublin, Poland, 20-090
- Targu Mures, Romania, 540136
- Kazan, Russian Federation, 4420029
- Kemerovo, Russian Federation, 650066
- Moscow, Russian Federation, 119435
- Belgrade, Serbia, 11000
- Nis, Serbia, 18000
- Bratislava, Slovakia, 833 05
- Kosice, Slovakia, 04011
- Spisska Nova Ves, Slovakia, 05201
- Zilina, Slovakia, 01001
- Dnepropetrovsk, Ukraine, 49027
- Donetsk, Ukraine, 83037
- Ivano-Frankivsk, Ukraine, 76008
- Kharkiv, Ukraine, 61000
- Vinnytsya, Ukraine, 21005Zaporizhzhya, Ukraine, 69057
Primary Outcome Measures:
- Reduction in cumulative total gadolinium (Gd)-enhancing MRI lesions. [Time Frame: Baseline, 24 weeks ]
Secondary Outcome Measures:
- Total number of Gd-enhancing MRI lesions. [ Time Frame: 4, 8, 12, 16, 20, 24, 30, 36, 42, and 48 weeks ]
- Total number of new or newly enlarging T2-weighted MRI lesions. [ Time Frame: 4, 8, 12, 16, 20, 24, 30, 36, 42, and 48 weeks ]
- Time to first relapse. [ Time Frame: Weeks 24, 48 and period in between. ]
- Proportion of relapse-free subjects. [ Time Frame: Weeks 24, 48 and period in between. ]
- Proportion of subjects with anti-LY2127399 antibodies. [ Time Frame: 24, 48, and 72 weeks ]
- Pharmacodynamics of selected peripheral B cell subsets. [ Time Frame: Week 72 ]
- Serum pharmacokinetics (AUC). [ Time Frame: 42 weeks ]
- Expanded Disability Status Scale (EDSS). [ Time Frame: 12, 24, and 48 weeks ]
- Multiple Sclerosis Functional Composite Scale (MSFC). [ Time Frame: 12, 24, and 48 weeks ]
- Visual Analog Scale (VAS) of Wellbeing. [ Time Frame: 12, 24, and 48 weeks ]
- Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). [ Time Frame: 12, 24, and 48 weeks ]
- 16-Item Quick Inventory for Depressive Symptomatology Self Report (QIDS-SR16). [ Time Frame: 12, 24, and 48 weeks ]
- Total number of new Gd-enhancing MRI lesions. [ Time Frame: 4, 8, 12, 16, 20, 24, 30, 36, 42, and 48 weeks ]
- Total volume of T2-weighted MRI lesions. [ Time Frame: 4, 8, 12, 16, 20, 24, 30, 36, 42, and 48 weeks ]
- Annualized relapse rate. [ Time Frame: Weeks 24 and 48. ]
Estimated Enrollment: 245
- Study Start Date: April 2009
- Study Completion Date: June 2012
- Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
- Ages Eligible for Study: 18 Years to 64 Years (Adult)
- Sexes Eligible for Study: All
- 18 through 64 years of age diagnosed with relapsing-remitting multiple sclerosis (RRMS), who can walk without aid or rest for at least 200 meters (approximately 1/10 of a mile).
- Women who can become pregnant must use birth control.
- Have had a live vaccination within 12 weeks before randomization, or intend to have a live vaccination during the course of the study.
- Have had had recent surgery or are scheduled to have surgery during the study.
- Are immunocompromised or have evidence of active infection (such as hepatitis, tuberculosis or, human immunodeficiency virus [HIV]).
- Have been on certain drugs that are being studied for RRMS or have recently received prescription drugs to treat RRMS.
- Have had a recent serious infection.
- Have serious or uncontrolled illnesses other than RRMS.
- Have clinically significant blood test values.
- Have multiple or severe drug allergies.
- Have contraindications for magnetic resonance imaging (MRI; “scanning”) or claustrophobia (fear of an enclosed space) that cannot be managed.
ClinicalTrials.gov identifier: NCT00882999
ClinicalTrials.gov Identifier: NCT00882999 History of Changes
Other Study ID Numbers: 12778 H9B-MC-BCDJ
Study First Received: April 16, 2009
Last Updated: June 22, 2012
Baker et al. Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis. EBioMedicine. 2017 Jan 31. pii: S2352-3964(17)30045-2.
Although multiple sclerosis (MS) is considered to be a CD4, Th17-mediated autoimmune disease, supportive evidence is perhaps circumstantial, often based on animal studies, and is questioned by the perceived failure of CD4-depleting antibodies to control relapsing MS. Therefore, it was interestingly to find that current MS-treatments, believed to act via T cell inhibition, including: beta-interferons, glatiramer acetate, cytostatic agents, dimethyl fumarate, fingolimod, cladribine, daclizumab, rituximab/ocrelizumab physically, or functionally in the case of natalizumab, also depleted CD19+, CD27+ memory B cells. This depletion was substantial and long-term following CD52 and CD20-depletion, and both also induced long-term inhibition of MS with few treatment cycles, indicating induction-therapy activity. Importantly, memory B cells were augmented by B cell activating factor (atacicept) and tumor necrosis factor (infliximab) blockade that are known to worsen MS. This creates a unifying concept centered on memory B cells that is consistent with therapeutic, histopathological and etiological aspects of MS.