title: Effectiveness and Safety of a Multicenter Extension and Retreatment Trial of Gel-200 in Patients with Knee Osteoarthritis.
abstract: OBJECTIVE
  To assess the continued effectiveness and safety of Gel-200 following observation and open-label retreatment in an extension protocol following a randomized, double-blind, phosphate buffered saline (PBS)-controlled trial (initial treatment trial).
  
  
  METHODS
  Patients who completed initial blinded treatment were allowed to enroll into this extension protocol that permitted retreatment with Gel-200 when eligibility criteria were met. Retreatment was administered with a Gel-200 injection, without knowledge of initial treatment assignment (Gel-200 or PBS). Retreated patients were followed for up to 13 weeks. In the extension phase, durability of response following the first injection was analyzed by time to retreatment eligibility. During separate extension and retreatment phases, responses were assessed by WOMAC pain, stiffness, and physical function subscores, total score, and global assessments of disease activity (patient, physician) as well as safety of Gel-200.
  
  
  RESULTS
  In the extension phase, time-to-event analyses through 26 weeks following the initial injection showed statistically significantly longer times to retreatment in patients receiving Gel-200 compared with PBS (P < 0.05). Retreatment with Gel-200, e.g., a second injection, resulted in statistically significant improvements from retreatment baseline in all outcome measures (P < 0.0001). The incidence and type of adverse events after retreatment were comparable to those observed following initial injection of Gel-200 without allergic reactions, including "pseudosepsis" or unanticipated treatment-related serious adverse events.
  
  
  CONCLUSIONS
  These data demonstrate that a single injection of Gel-200 resulted in durable effectiveness through 26 weeks and that repeated treatment with Gel-200 relieved symptomatic osteoarthritis with a favorable safety profile.
authors.affiliation: Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, CA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Strand
authors.affiliation: The Center for Rheumatology and Bone Research, Wheaton, MD, USA.
authors.forename: H S B
authors.initials: HS
authors.lastname: Baraf
authors.affiliation: Boston Biostatistics Research Foundation, Framingham, MA, USA.
authors.forename: P T
authors.initials: PT
authors.lastname: Lavin
authors.affiliation: Biostatistics & Data Management Group, Clinical Development Department, Research & Development Division, Seikagaku Corporation, Chiyoda-ku, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Lim
authors.affiliation: Clinical Development Department, Research & Development Division, Seikagaku Corporation, Chiyoda-ku, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hosokawa
keywords: Gel-200; clinical trial; intra-articular delivery; knee; osteoarthritis