Safety Study of Repeated, Escalating Doses of Intradermal Avotermin (Juvista)
Condition: Cicatrix; Wound Healing
MeSH terms: Cicatrix
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine the safety and local toleration and histological
      effects of various dose levels of avotermin (Juvista) injected intradermally in healthy male
      volunteers.
    

Detailed description: 
      The study was split into two Cohorts: A and B. Volunteers in Cohort A were assigned to one of
      four dose groups receiving 50, 100, 500 and 1000ng/100μl/3mm punch biopsy. Volunteers were
      assigned sequentially in order of ascending dose. Within each dose group volunteers were
      further randomised to subgroup a, b or c. Each subject was set to receive four 3mm punch
      biopsies, two on each arm, and intradermal injection of avotermin, placebo or nothing
      (standard care).

      On day 0 two 3mm punch biopsies were administered under local anaesthesia to the inner aspect
      of one arm of each subject following intradermal injection of avotermin, placebo or nothing.
      The four subjects in subgroup a received avotermin to one punch biopsy and placebo to the
      other. The four subjects in subgroup b received avotermin to one punch biopsy and standard
      care only to the other. The one subject in subgroup c was administered with intradermal
      placebo to one biopsy and standard care only to the other. 24 h later a further application
      of intradermal avotermin, placebo or nothing was applied.

      While arm 1 was used as a study arm, arm 2 was used for safety procedures. Subjects were then
      randomised to return on Day 3 or 7 for excision of the first two punch biopsies. At the same
      time two punch biopsies and the same treatment regime was carried out on the second arm.
      These were dosed again 24 h later and all were excised on Day 10.

      After determining safety and toleration of all doses in Cohort A, new subjects were assigned
      to Cohort B. These were allocated in ascending order to groups that would receive 1, 10, 50
      and 100μg/100μl/3mm punch biopsy, following the same procedures that were used for Cohort A.
      Only after the first three groups reached Day 10 and the safety data was analysed would the
      final volunteers be recruited to the 100μg group.
    

Intervention name(s): Avotermin; Avotermin; Avotermin; Avotermin; Avotermin; Avotermin; Placebo (vehicle)
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Intradermal injection, 50ng/100μl/3mm punch biopsy, once at time of biopsy and again 24 h later; Intradermal injection, 100ng/100μl/3mm punch biopsy, once at time of biopsy and again 24 h later; Intradermal injection, 500ng/100μl/3mm punch biopsy, once at time of biopsy and again 24 h later; Intradermal injection, 1000ng/100μl/3mm punch biopsy, once at time of biopsy and again 24 h later; Intradermal injection, 1μg/100μl/3mm punch biopsy, once at time of biopsy and again 24 h later; Intradermal injection, 10μg/100μl/3mm punch biopsy, once at time of biopsy and again 24 h later; Intradermal injection at time of biopsy and again 24 h later
Other intervention name(s): RN1001; Juvista; TGFbeta 3; RN1001; Juvista; TGFbeta 3; RN1001; Juvista; TGFbeta 3; RN1001; Juvista; TGFbeta 3; RN1001; Juvista; TGFbeta 3; RN1001; Juvista; TGFbeta 3
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Cicatrix; Scar; Wound healing; Avotermin; TGF beta 3; Juvista; RN1001