Investigation of the Safety, Dosing Frequency and Anti-Scarring Potential of Two Concentrations of Intradermal Avotermin (Juvista)

NCT ID: NCT00978367

Last Updated: 2009-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-02-28
• Study Completion Date: 2002-11-30

Brief 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.

Conditions

Cicatrix; Wound Healing; Re-epithelialization

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Drug, intradermal avotermin (Juvista)

Group Type: EXPERIMENTAL

Avotermin

Intervention Type: DRUG

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

Avotermin

Intervention Type: DRUG

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.

Avotermin

Intervention Type: DRUG

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 (vehicle)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

Avotermin

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

Intervention Type: DRUG

Avotermin

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.

Intervention Type: DRUG

Avotermin

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

Juvista; RN1001; TGF beta 3; Juvista; RN1001; TGF beta 3; Juvista; RN1001; TGF beta 3

Eligibility Criteria

Inclusion Criteria

• Healthy, non-Caribbean, male subjects aged 18-45 years inclusive
• Weight between 60-150 kg and a BMI within the permitted range for their height using Quetelet's index (15-45 kg/m(squared)) (weight (kg)/height (squared)(m))
• Subjects who have a previous history of surgery or minor injury and who have not developed any evidence of hypertrophic or keloid scar formation

Exclusion Criteria

• Subjects who have a history or evidence of hypertrophic or keloid scarring
• Subjects with tattoos or previous scars in the area to be biopsied
• Subjects who have evidence of any past or present clinically significant disease, particularly coagulation disorders

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Renovo

INDUSTRY

Sponsor Role: lead

Responsible Party

Renovo Ltd

Principal Investigators

Michael J Davies

Role: PRINCIPAL_INVESTIGATOR

Renovo

Jonathan Duncan

Role: PRINCIPAL_INVESTIGATOR

Renovo

Locations

Renovo Ltd

Manchester, , United Kingdom

Countries

United Kingdom

Other Identifiers

RN1001-319-1003

Identifier Type: -

Identifier Source: org_study_id