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

Wound Healing Clinical Trial

Official title:

A Double Blind, Placebo (Vehicle) and Standard Care Controlled, Randomised Study to Investigate the Clinical Safety and Toleration (Including Systemic Pharmacokinetics), Wound Healing and Anti-scarring Potential of Two Applications of Intradermal RN1001 in Healthy Male Subjects.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00978367
• Other study ID #: RN1001-319-1003
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 15, 2009
• Last updated: September 15, 2009
• Start date: February 2002
• Est. completion date: November 2002

Study information

• Verified date: September 2009
• Source: Renovo
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: November 2002
• Est. primary completion date: November 2002
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cicatrix
• Re-epithelialization
• Wound Healing

Intervention

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 day 5 just prior to excision of the wound with a 5 mm surgical ellipse
• 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.
• 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.
• 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
• 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.
• 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.

Locations

Country	Name	City	State
United Kingdom	Renovo Ltd	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Renovo

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the dosing frequency of various concentrations of intradermal avotermin (Juvista) for the improvement of early wound healing and re-epithelialisation, as determined by measuring total wound diameter		Day 5 post surgery	No
Secondary	To determine the safety and toleration of various concentrations of avotermin (Juvista) applied by intradermal injection at various timepoints		Days 0-14 post-wounding	Yes
Secondary	To determine the systemic exposure of various concentrations of avotermin (Juvista) applied by intradermal injection at various timepoints		Days 0-14 post-wounding	Yes
Secondary	To determine the gross and histological endpoints (re-epithelialisation and wound healing) of various concentrations of avotermin (Juvista) applied by intradermal injection at various dosing frequencies		0-6 months post-wounding	No
Secondary	To determine the anti-scarring potential of two doses of avotermin (Juvista) when applied by intradermal injection at various dosing frequencies		Day 5 and 6 months post-wounding	No