title: The results of two multicenter, open-label studies assessing efficacy, tolerability and safety of protiramer, a high molecular weight synthetic copolymeric mixture, in patients with relapsing-remitting multiple sclerosis.
abstract: OBJECTIVE
  Two pilot studies were conducted to evaluate safety, tolerability, and efficacy of two doses of Protiramer (TV-5010) in patients with relapsing-remitting multiple sclerosis.
  
  
  BACKGROUND
  Both glatiramer acetate and TV-5010 are synthetic copolymers comprised the same four amino acids in a defined molar ratio. TV-5010 has higher average molecular weight than Glatiramer acetate and might be hypothesized that glatiramoids with higher molecular weight might be more immunoreactive than lower molecular weight peptides, thus increasing therapeutic potential and allowing for less frequent dosing.
  
  
  METHODS
  In the two separate studies, after a 10 week pretreatment period, TV-5010 was given subcutaneously once weekly at 15 mg and 30 mg for 36 weeks. The primary end point was a reduction in the number of magnetic resonance imaging active lesions (i.e., T1-weigthed gadolinium-enhancing and new T2-weighted lesions) between the pretreatment period and the end of study.
  
  
  RESULTS
  Both TV-5010 doses were generally well tolerated. The treatment with TV-5010 at a dose of 15 mg/wk did not show any significant effect. In contrast, in patients treated with at a dose of 30 mg/wk, a significant reduction in the mean number of gadolinium-enhancing (-58.8%; P = 0.0013) and new T2-W (-50%; P = 0.0002) lesions was observed. However, a large decrease in the mean number of both gadolinium-enhancing (-55%) and new T2-W (-40%) lesions during the pretreatment period made difficult the interpretation of the efficacy assessments.
  
  
  CONCLUSIONS
  Further studies are needed to confirm these preliminary data on safety and efficacy of TV-5010 at a weekly dose of 30 mg.
authors.affiliation: Neurology and Neurometabolic Unit, Department of Neurological & Behavioral Sciences, University of Siena, Siena, Italy. destefano@unisi.it
authors.forename: N
authors.initials: N
authors.lastname: De Stefano
authors.forename: M
authors.initials: M
authors.lastname: Filippi
authors.forename: C
authors.initials: C
authors.lastname: Confavreux
authors.forename: P
authors.initials: P
authors.lastname: Vermersch
authors.forename: M
authors.initials: M
authors.lastname: Simu
authors.forename: C
authors.initials: C
authors.lastname: Sindic
authors.forename: R
authors.initials: R
authors.lastname: Hupperts
authors.forename: O
authors.initials: O
authors.lastname: Bajenaru
authors.forename: G
authors.initials: G
authors.lastname: Edan
authors.forename: L
authors.initials: L
authors.lastname: Grimaldi
authors.forename: I
authors.initials: I
authors.lastname: Marginean
authors.forename: R
authors.initials: R
authors.lastname: Medaer
authors.forename: G
authors.initials: G
authors.lastname: Orefice
authors.forename: I
authors.initials: I
authors.lastname: Pascu
authors.forename: J
authors.initials: J
authors.lastname: Pelletier
authors.forename: E
authors.initials: E
authors.lastname: Sanders
authors.forename: E
authors.initials: E
authors.lastname: Scarpini
authors.forename: G L
authors.initials: GL
authors.lastname: Mancardi
mesh_terms: D000328:Adult; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D007279:Injections, Subcutaneous; D008297:Male; D008970:Molecular Weight; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D010455:Peptides; D000068717:Glatiramer Acetate