title: Randomized phase I trials of the safety/tolerability of anti-LINGO-1 monoclonal antibody BIIB033.
abstract: OBJECTIVE
  To evaluate the safety, tolerability, and pharmacokinetics (PK) of BIIB033 (anti-LINGO-1 monoclonal antibody) in healthy volunteers and participants with multiple sclerosis (MS).
  
  
  METHODS
  In 2 separate randomized, placebo-controlled studies, single ascending doses (SAD; 0.1-100 mg/kg) of BIIB033 or placebo were administered via IV infusion or subcutaneous injection to 72 healthy volunteers, and multiple ascending doses (MAD; 0.3-100 mg/kg; 2 doses separated by 14 days) of BIIB033 or placebo were administered via IV infusion to 47 participants with relapsing-remitting or secondary progressive MS. Safety assessments included adverse event (AE) monitoring, neurologic examinations, conventional and nonconventional MRI, EEG, optical coherence tomography, retinal examinations, and evoked potentials. Serum and CSF PK as well as the immunogenicity of BIIB033 were also evaluated.
  
  
  RESULTS
  All 72 healthy volunteers and 47 participants with MS were included in the safety analyses. BIIB033 infusions were well tolerated. The frequency of AEs was similar between BIIB033 and placebo. There were no serious AEs or deaths. No clinically significant changes in any of the safety measures were observed. BIIB033 PK was similar between healthy volunteers and participants with MS. Doses of ≥10 mg/kg resulted in BIIB033 concentrations similar to or higher than the concentration associated with 90% of the maximum remyelination effect in rat remyelination studies. The incidence of anti-drug antibody production was low.
  
  
  CONCLUSIONS
  The emerging safety, tolerability, and PK of BIIB033 support advancing BIIB033 into phase II clinical development as a potential treatment for CNS demyelination disorders.
  
  
  METHODS
  This study provides Class I evidence that BIIB033 is well tolerated and safe (serious adverse event rate 0%, 95% confidence interval 0-7.6%).
authors.affiliation: Biogen Idec (J.Q.T., J.R., S.R., L.X., D.C.), Cambridge, MA; VU Medical Center (F.B., M.P.W., R.D.), Amsterdam, the Netherlands; IMMUNOe (I.M.), Centennial, CO; PAREXEL International (H.G.), Glendale, CA; ALG Partners (K.B.), Natick, MA; and Excel Scientific Solutions (E.P.), Southport, CT. J.Z. is a former employee of Biogen Idec.
authors.forename: Jonathan Q
authors.initials: JQ
authors.lastname: Tran
authors.affiliation: Biogen Idec (J.Q.T., J.R., S.R., L.X., D.C.), Cambridge, MA; VU Medical Center (F.B., M.P.W., R.D.), Amsterdam, the Netherlands; IMMUNOe (I.M.), Centennial, CO; PAREXEL International (H.G.), Glendale, CA; ALG Partners (K.B.), Natick, MA; and Excel Scientific Solutions (E.P.), Southport, CT. J.Z. is a former employee of Biogen Idec.
authors.forename: Jitesh
authors.initials: J
authors.lastname: Rana
authors.affiliation: Biogen Idec (J.Q.T., J.R., S.R., L.X., D.C.), Cambridge, MA; VU Medical Center (F.B., M.P.W., R.D.), Amsterdam, the Netherlands; IMMUNOe (I.M.), Centennial, CO; PAREXEL International (H.G.), Glendale, CA; ALG Partners (K.B.), Natick, MA; and Excel Scientific Solutions (E.P.), Southport, CT. J.Z. is a former employee of Biogen Idec.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Biogen Idec (J.Q.T., J.R., S.R., L.X., D.C.), Cambridge, MA; VU Medical Center (F.B., M.P.W., R.D.), Amsterdam, the Netherlands; IMMUNOe (I.M.), Centennial, CO; PAREXEL International (H.G.), Glendale, CA; ALG Partners (K.B.), Natick, MA; and Excel Scientific Solutions (E.P.), Southport, CT. J.Z. is a former employee of Biogen Idec.
authors.forename: Isaac
authors.initials: I
authors.lastname: Melamed
authors.affiliation: Biogen Idec (J.Q.T., J.R., S.R., L.X., D.C.), Cambridge, MA; VU Medical Center (F.B., M.P.W., R.D.), Amsterdam, the Netherlands; IMMUNOe (I.M.), Centennial, CO; PAREXEL International (H.G.), Glendale, CA; ALG Partners (K.B.), Natick, MA; and Excel Scientific Solutions (E.P.), Southport, CT. J.Z. is a former employee of Biogen Idec.
authors.forename: Hakop
authors.initials: H
authors.lastname: Gevorkyan
authors.affiliation: Biogen Idec (J.Q.T., J.R., S.R., L.X., D.C.), Cambridge, MA; VU Medical Center (F.B., M.P.W., R.D.), Amsterdam, the Netherlands; IMMUNOe (I.M.), Centennial, CO; PAREXEL International (H.G.), Glendale, CA; ALG Partners (K.B.), Natick, MA; and Excel Scientific Solutions (E.P.), Southport, CT. J.Z. is a former employee of Biogen Idec.
authors.forename: Mike P
authors.initials: MP
authors.lastname: Wattjes
authors.affiliation: Biogen Idec (J.Q.T., J.R., S.R., L.X., D.C.), Cambridge, MA; VU Medical Center (F.B., M.P.W., R.D.), Amsterdam, the Netherlands; IMMUNOe (I.M.), Centennial, CO; PAREXEL International (H.G.), Glendale, CA; ALG Partners (K.B.), Natick, MA; and Excel Scientific Solutions (E.P.), Southport, CT. J.Z. is a former employee of Biogen Idec.
authors.forename: Remko
authors.initials: R
authors.lastname: de Jong
authors.affiliation: Biogen Idec (J.Q.T., J.R., S.R., L.X., D.C.), Cambridge, MA; VU Medical Center (F.B., M.P.W., R.D.), Amsterdam, the Netherlands; IMMUNOe (I.M.), Centennial, CO; PAREXEL International (H.G.), Glendale, CA; ALG Partners (K.B.), Natick, MA; and Excel Scientific Solutions (E.P.), Southport, CT. J.Z. is a former employee of Biogen Idec.
authors.forename: Kristin
authors.initials: K
authors.lastname: Brosofsky
authors.affiliation: Biogen Idec (J.Q.T., J.R., S.R., L.X., D.C.), Cambridge, MA; VU Medical Center (F.B., M.P.W., R.D.), Amsterdam, the Netherlands; IMMUNOe (I.M.), Centennial, CO; PAREXEL International (H.G.), Glendale, CA; ALG Partners (K.B.), Natick, MA; and Excel Scientific Solutions (E.P.), Southport, CT. J.Z. is a former employee of Biogen Idec.
authors.forename: Soma
authors.initials: S
authors.lastname: Ray
authors.affiliation: Biogen Idec (J.Q.T., J.R., S.R., L.X., D.C.), Cambridge, MA; VU Medical Center (F.B., M.P.W., R.D.), Amsterdam, the Netherlands; IMMUNOe (I.M.), Centennial, CO; PAREXEL International (H.G.), Glendale, CA; ALG Partners (K.B.), Natick, MA; and Excel Scientific Solutions (E.P.), Southport, CT. J.Z. is a former employee of Biogen Idec.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Biogen Idec (J.Q.T., J.R., S.R., L.X., D.C.), Cambridge, MA; VU Medical Center (F.B., M.P.W., R.D.), Amsterdam, the Netherlands; IMMUNOe (I.M.), Centennial, CO; PAREXEL International (H.G.), Glendale, CA; ALG Partners (K.B.), Natick, MA; and Excel Scientific Solutions (E.P.), Southport, CT. J.Z. is a former employee of Biogen Idec.
authors.forename: Jim
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Biogen Idec (J.Q.T., J.R., S.R., L.X., D.C.), Cambridge, MA; VU Medical Center (F.B., M.P.W., R.D.), Amsterdam, the Netherlands; IMMUNOe (I.M.), Centennial, CO; PAREXEL International (H.G.), Glendale, CA; ALG Partners (K.B.), Natick, MA; and Excel Scientific Solutions (E.P.), Southport, CT. J.Z. is a former employee of Biogen Idec.
authors.forename: Edward
authors.initials: E
authors.lastname: Parr
authors.affiliation: Biogen Idec (J.Q.T., J.R., S.R., L.X., D.C.), Cambridge, MA; VU Medical Center (F.B., M.P.W., R.D.), Amsterdam, the Netherlands; IMMUNOe (I.M.), Centennial, CO; PAREXEL International (H.G.), Glendale, CA; ALG Partners (K.B.), Natick, MA; and Excel Scientific Solutions (E.P.), Southport, CT. J.Z. is a former employee of Biogen Idec.
authors.forename: Diego
authors.initials: D
authors.lastname: Cadavid