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`Meeting on 27 August 2003 in Amsterdam
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`SeronoParticipants:
`I, Emery, G. Francis, D. Frank, M. Lopez-Bresnahan, A. Munafo, A. Ythier, A. Jaber, by phone: N. Ammoury, J.
`Hillier
`IVAX Participants:
`S. Marcus, Y. Dandiker, D. Weiner, by phone: D. Emma
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`ORALCLADRIBINEforMSPROJECT|_—sMeeting 25 August 2003 - Amsterdam "Draft minutes- page 1 of8
`Merck 2079
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`TWi v Merck
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`IPR2023-00050
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`se I study with the
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`cyclodextrin formulation
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`Draft minutes - page 2 of 8
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`ORAL CLADRIBINE for MS PROJECT
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`Yogesh discussed formulation rorsI Soft cet capsule,Si
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`Expert Panel andPhaseIIIdesign
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`Suggestions for primary phase III study (PB-controlled):
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`Arms: cumulative dose approximating 0.7 mg/kg (.35 mg/kg x 5 days x 2 months) and 2.1 mg/kg (.35
`ma/ka x 5 days x 6 months) and placebo
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`Duration of treatment: 24 months
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`ORAL CLADRIBINE for MS PROJECT
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`Phase III design issues to be fine tuned:
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`Efficacy endpoints : ROW experts agreed that relapse rate was the best primary endpoint, but time to first
`relapse will also be considered. Secondary end points discussed: MRI endpoints to be determined with
`suggestion that majority of sites perform MRI at baseline, 12 & 24 months with a subset of sites doing
`frequent MRI (baseline, 9, 10, 11, 12, 21, 22, 23 & 24 months), disability at 2 or 3 years, safety,
`pharmacodynamics (lymphocyte markers), consider surrogate marker used in HIV study (Trex, an increase in
`marker indicates maintenance of stem cel! pool)
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`Sample size: dropout rate estimated at 20%
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`@ Regulatory Strategy (Jill Hiller/I. Emery)
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`ORAL CLADRIBINE for MS PROJECT
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`ORAL CLADRIBINE for MS PROJECT _—“ Meeting 25 August 2003 - Amsterdam
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