Study to Evaluate Efficacy of OLX10010 in Reducing Recurrence of Hypertrophic Scarring After Scar Revision Surgery
Condition: Hypertrophic Scar
MeSH terms: Recurrence; Hypertrophy; Cicatrix, Hypertrophic
Study type: Interventional
Phase: Phase 2

Summary: 
      Phase 2a, prospective, randomized, double-blind, intra-subject, placebo-controlled, proof of
      concept study. Approximately twenty subjects will be randomized 1:1 to one of two treatment
      arms:

      Arm A: 2.0 mg/cm OLX10010 biweekly (every two weeks) Arm B: 5.0 mg/cm OLX10010 biweekly
      (every two weeks) Each treatment arm will have approximately 10 subjects. Each subject will
      receive both active (OLX10010) and control (placebo) treatment post-hypertrophic scar surgery
      biweekly (every two weeks) for a total of six doses. Dosing will occur post-surgery on Weeks
      2, 4, 6, 8, 10, and 12. Post-treatment follow-up visits will occur at Weeks 18 and 24, and a
      long-term follow-up visit will occur at Month 12. The Patient and Observer Scar Assessment
      Scale (both physician and patient scales), Stony Brook Scar Evaluation Scale, Vancouver Scar
      Scale, and a photograph-based visual analog scale by blinded experts will be completed prior
      to scar revision surgery, at Weeks 2, 8, 12, 18, and 24, and at Month 12. The overall opinion
      responses on the physician scales of the POSAS at Week 24 will be used for primary endpoint
      analysis.

      The total length of the linear hypertrophic scar line will be divided equally for treatment
      with OLX10010 and placebo, injected intradermally per centimeter (cm). The OLX10010 end and
      placebo end of the scar line will be separated by a 2 cm or greater distance depending on the
      scar length.

      After the Week 24 visit, all data collected will be cleaned and all data management
      activities will be completed. After the database is frozen/locked, the primary endpoint
      efficacy analysis will be completed. If at least one of the treatment arms are shown to be
      appropriate to reduce recurrence of hypertrophic scars, all analyses will be performed. If
      the efficacy analysis of Arms A and B indicate the study doses are not as effective as
      expected, the sponsor may decide to add a third arm (Arm C) to explore the weekly dosing
      regimen. See detailed summary.

      Subjects in all study arms will continue in the study until their Month 12 visit. After all
      subjects complete that visit, data are collected, and data management activities are
      completed, Month 12 data will be analyzed.
    

Detailed description: 
      This is a Phase 2a, prospective, randomized, double-blind, intra-subject, placebo-controlled,
      proof of concept study. Approximately twenty subjects will be randomized 1:1 to one of two
      treatment arms:

      Arm A: 2.0 mg/cm OLX10010 biweekly (every two weeks) Arm B: 5.0 mg/cm OLX10010 biweekly
      (every two weeks) Each treatment arm will have approximately 10 subjects. Each subject will
      receive both active (OLX10010) and control (placebo) treatment post-hypertrophic scar surgery
      biweekly (every two weeks) for a total of six doses. Dosing will occur post-surgery on Weeks
      2, 4, 6, 8, 10, and 12. Post-treatment follow-up visits will occur at Weeks 18 and 24, and a
      long-term follow-up visit will occur at Month 12. The Patient and Observer Scar Assessment
      Scale (both physician and patient scales), Stony Brook Scar Evaluation Scale, Vancouver Scar
      Scale, and a photograph-based visual analog scale by blinded experts will be completed prior
      to scar revision surgery, at Weeks 2, 8, 12, 18, and 24, and at Month 12. The overall opinion
      responses on the physician scales of the POSAS at Week 24 will be used for primary endpoint
      analysis.

      The total length of the linear hypertrophic scar line will be divided equally for treatment
      with OLX10010 and placebo, injected intradermally per centimeter (cm). The OLX10010 end and
      placebo end of the scar line will be separated by a distance of 2 cm or greater depending on
      the scar length.

      After the Week 24 visit, all data collected will be cleaned and all data management
      activities will be completed. After the database is frozen/locked, the primary endpoint
      efficacy analysis will be completed. If at least one of the treatment arms are shown to be
      appropriate to reduce recurrence of hypertrophic scars, all analyses will be performed. If
      the efficacy analysis of Arms A and B indicate the study doses are not as effective as
      expected, the sponsor may decide to add a third arm (Arm C) to explore the weekly dosing
      regimen:

      Arm C: 2.0 mg/cm OLX10010 weekly If added, Arm C will enroll 10 subjects. Each subject will
      receive both active (OLX10010) and control (placebo) treatment post-hypertrophic scar surgery
      weekly for a total of 11 doses. Dosing will occur post-surgery on Weeks 2, 3, 4, 5, 6, 7, 8,
      9, 10, 11, and 12. Post-treatment follow-up visits will occur on Weeks 18 and 24, and a
      long-term follow-up visit will occur at Month 12. The Patient and Observer Scar Assessment
      Scale (both physician and patient scales), Stony Brook Scar Evaluation Scale, Vancouver Scar
      Scale, and a photograph-based visual analog scale by two blinded independent assessors will
      be completed prior to scar revision surgery, at Weeks 2, 8, 12, 18, and 24, and at Month 12.
      The overall opinion responses on the physician scales of the POSAS at Week 24 will be used
      for primary endpoint analysis. After all subjects in Arm C complete Week 24, all data are
      collected, and all data management activities are completed, a new database freeze/lock will
      be performed. Arm C data will be analyzed.

      Subjects in all study arms will continue in the study until their Month 12 visit. After all
      subjects complete that visit, data are collected, and data management activities are
      completed, Month 12 data will be analyzed.
    

Intervention name(s): OLX10010
Intervention type(s): Drug
Intervention description(s): Lyophilized cake reconstituted with WFI and injected intradermally
Other intervention name(s): a cell penetrating asymmetric small interference RNA (cp-asiRNA), targeting a gene involved in formation of fibrosis
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 2 parallel arms and then a 3rd arm will be enrolled if the endpoints for the first 2 arms aren't met.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: scar revision surgery; OLX10010; siRNA