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

Sponsor

Renovo (Industry)

Overall Status

Completed

CT.gov ID

NCT00978367

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

4.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cicatrix Wound Healing Re-epithelialization	Drug: Avotermin Drug: Avotermin Drug: Avotermin Drug: Placebo Drug: Placebo Drug: Placebo	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

43 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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.

Study Start Date :

Feb 1, 2002

Actual Primary Completion Date :

Nov 1, 2002

Actual Study Completion Date :

Nov 1, 2002

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Drug, intradermal avotermin (Juvista)	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 Other Names: Juvista RN1001 TGF beta 3 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. Other Names: Juvista RN1001 TGF beta 3 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. Other Names: Juvista RN1001 TGF beta 3
Placebo Comparator: Placebo (vehicle)	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 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. 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.

Arm

Intervention/Treatment

Experimental: Drug, intradermal avotermin (Juvista)

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

Other Names:

Juvista

RN1001

TGF beta 3

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.

Other Names:

Juvista

RN1001

TGF beta 3

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.

Other Names:

Juvista

RN1001

TGF beta 3

Placebo Comparator: Placebo (vehicle)

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

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.

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.

Outcome Measures

Primary Outcome Measures

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]

Secondary Outcome Measures

To determine the safety and toleration of various concentrations of avotermin (Juvista) applied by intradermal injection at various timepoints [Days 0-14 post-wounding]
To determine the systemic exposure of various concentrations of avotermin (Juvista) applied by intradermal injection at various timepoints [Days 0-14 post-wounding]
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]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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