A total of 188 patients are planned for the multi-center study. Upon enrollment, patients will be randomly assigned to one of four treatment group: placebo, methylprednisolone 1 gram IV daily for 3 days, Hu23F2G 1 mg/kg IV, or Hu23F2G 2 mg/kg IV. The subjects will be followed for one year after treatment in order to assess the early changes related to the acute exacerbation (Day 0 to Day 90) as well as the subsequent course (Day 91 to Day 365). The clinical response to treatment will be measured by a neurologic examination form which three numerical scores are derived: the Scripps score, the sum of the Functional System (FS), and modified Expanded Disability Status Scale (EDSS). The primary endpoint will be the change in Scripps score form Day 0 through Day 90. The Scripps score was selected as the primary outcome measure because we hypothesize that it will be more sensitive to change in the setting of an acute exacerbation than the other two scores. The change in the sum of the FS and EDSS form Day 0 through Day 90 will be secondary endpoints. MRI of the brain will be obtained prior to treatment and on Day 5. The change in the extent of abnormalities detected on the MRI form Day 0 to Day 5 will be a secondary endpoint. Since corticosteroid rescue will be available for patients deemed to have failed the assigned treatment, the time to corticosteroid rescue will be a secondary endpoint. The clinical course over the year following treatment will be assessed by determining the time to the next exacerbation and the EDSS on Day 365; these parameters will also be secondary endpoints. The in vitro biologic activity and in vivo efficacy of Hu23F2G in a nonhuman primate model of experimental allergic encephalomyelitis (EAE) support a potential application in the treatment of MS. The acute exacerbation component of MS will be studied under this protocol. The rationale is that the EAE model is associated with acute onset of neurologic deficits and new lesions in the central nervous system (CNS), events that are analogous to the acute MS exacerbation. In the acute exacerbation setting, a treatment commonly offered is three to five days of corticosteroids. This treatment duration is comparable to the duration of maximal pharmacodynamic effects observed after a single IV dose of 1 to 2 mg/kg of Hu23F2G in Phase 1 studies. Since corticosteroids therapy is currently used for many patients with acute exacerbations, in this study the effects of Hu23F2G treatment will be compared to a standard corticosteroid regimen along with placebo. Corticosteroid therapy will also be available for patients deemed to have failed the assigned treatment.
| Burgess-Hull, Albert J; Roberts, Linda J; Piper, Megan E et al. (2018) The social networks of smokers attempting to quit: An empirically derived and validated classification. Psychol Addict Behav 32:64-75 |
| Kelly, Elizabeth A; Esnault, Stephane; Liu, Lin Ying et al. (2017) Mepolizumab Attenuates Airway Eosinophil Numbers, but Not Their Functional Phenotype, in Asthma. Am J Respir Crit Care Med 196:1385-1395 |
| Shen, Zhong-Jian; Hu, Jie; Kashi, Venkatesh P et al. (2017) Epstein-Barr Virus-induced Gene 2 Mediates Allergen-induced Leukocyte Migration into Airways. Am J Respir Crit Care Med 195:1576-1585 |
| Anderson, Halie M; Lemanske Jr, Robert F; Evans, Michael D et al. (2017) Assessment of wheezing frequency and viral etiology on childhood and adolescent asthma risk. J Allergy Clin Immunol 139:692-694 |
| Gomez, Jose L; Yan, Xiting; Holm, Carole T et al. (2017) Characterisation of asthma subgroups associated with circulating YKL-40 levels. Eur Respir J 50: |
| Kelly, Elizabeth A; Esnault, Stephane; Johnson, Sean H et al. (2016) Human eosinophil activin A synthesis and mRNA stabilization are induced by the combination of IL-3 plus TNF. Immunol Cell Biol 94:701-8 |
| Bray, Bethany C; Smith, Rachel A; Piper, Megan E et al. (2016) Transitions in Smokers' Social Networks After Quit Attempts: A Latent Transition Analysis. Nicotine Tob Res 18:2243-2251 |
| Dougherty, Ryan J; Ellingson, Laura D; Schultz, Stephanie A et al. (2016) Meeting physical activity recommendations may be protective against temporal lobe atrophy in older adults at risk for Alzheimer's disease. Alzheimers Dement (Amst) 4:14-7 |
| Johansson, Mats W; Evans, Michael D; Crisafi, Gina M et al. (2016) Serum periostin is associated with type 2 immunity in severe asthma. J Allergy Clin Immunol 137:1904-1907.e2 |
| Kolesar, Jill M; Pomplun, Marcia; Havighurst, Tom et al. (2015) Soy food frequency questionnaire does not correlate with baseline isoflavone levels in patients with bladder cancer. J Oncol Pharm Pract 21:128-31 |
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