Investigation of the Safety, Dosing Frequency and Anti-Scarring Potential of Two Concentrations of Intradermal Avotermin (Juvista)
Condition: Cicatrix; Wound Healing; Re-epithelialization
MeSH terms: Cicatrix
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to investigate the dosing frequency, wound healing
      (re-epithelialisation) and anti-scarring effects of one, three and five applications of two
      concentrations of intradermal RN1001 in healthy male subjects.
    

Detailed description: 
      Subjects were randomised into two cohorts, to receive either 5 ng avotermin doses or 50 ng
      doses, with a minimum of 21 subjects per cohort. Within each cohort subjects were randomised
      into one of three dosing groups (7 subjects per group).

      Subjects were to receive four 3 mm punch biopsies, two on the upper-inner aspect of each arm.
      One treatment was randomly allocated to one biopsy on one arm, with the opposite biopsy on
      the other arm set to receive the same treatment. The other treatment was administered to the
      other two biopsies (one on each arm. This allowed for control of possible positional effects
      on healing.

      Three subjects per group received intradermal avotermin to one of the biopsies on each arm
      and intradermal placebo to the other biopsies. A different three subjects received
      intradermal avotermin to one of the biopsies on each arm and standard care only to the other
      biopsies. The final subject per group received intradermal placebo to one of the biopsies on
      each arm and standard care only to the other biopsy.

      On day 0 biopsy sites were marked on both arms and following local anaesthesia avotermin,
      placebo or nothing was injected intradermally into the allocated sites. Subjects in dosing
      frequency group 1 (DFG 1) were dosed only once (day 0), subjects in DFG 2 were dosed three
      times (day 0, 1 and 2) and subjects in DFG 3 were dosed five times (day 0, 1, 2, 3 and 4).

      On Day 5, all subjects had their punch biopsy wounds on one arm only re-dosed as per Day 0
      and then excised with a 5 mm surgical ellipse. Subjects in DFG2 and DFG3 received further
      re-dosing on their excised punch biopsies as before, i.e. three doses for DFG2 and five doses
      for DFG3.

      Subjects returned for a first follow-up at day 14 and then at months 2, 4 and 6 to examine
      for anti-scarring effects. At month 6 all scars were excised for histological examination.
    

Intervention name(s): Avotermin; Avotermin; Avotermin; Placebo; Placebo; Placebo
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 5 ng or 50 ng/100 ul avotermin applied by intradermal injection to one of two 3 mm punch biopsies on each arm just prior to surgery (on day 0) and again on day 5 just prior to excision of the wound with a 5 mm surgical ellipse; 5 ng or 50 ng/100 ul avotermin applied by intradermal injection to one of two 3 mm punch biopsies on each arm just prior to surgery (on day 0) and again on days 1 and 2. Dosing is repeated on day 5 (just prior to excision of the wound with a 5 mm surgical ellipse), 6 and 7.; 5 ng or 50 ng/100 ul avotermin applied by intradermal injection to one of two 3 mm punch biopsies on each arm just prior to surgery (on day 0) and again on days 1, 2, 3 and 4. Dosing is repeated on day 5 (just prior to excision of the wound with a 5 mm surgical ellipse), 6, 7, 8 and 9.; Placebo applied by intradermal injection to one of two 3 mm punch biopsies on each arm just prior to surgery (on day 0) and again on day 5 just prior to excision of the wound with a 5 mm surgical ellipse; Placebo applied by intradermal injection to one of two 3 mm punch biopsies on each arm just prior to surgery (on day 0) and again on days 1 and 2. Dosing is repeated on day 5 (just prior to excision of the wound with a 5 mm surgical ellipse), 6 and 7.; Placebo applied by intradermal injection to one of two 3 mm punch biopsies on each arm just prior to surgery (on day 0) and again on days 1, 2, 3 and 4. Dosing is repeated on day 5 (just prior to excision of the wound with a 5 mm surgical ellipse), 6, 7, 8 and 9.
Other intervention name(s): Juvista; RN1001; TGF beta 3; Juvista; RN1001; TGF beta 3; Juvista; RN1001; TGF beta 3
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Cicatrix; Scar; Avotermin; Juvista; RN1001; TGF beta 3