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Genomic Changes Associated With the Use of Intradermal Avotermin (Juvista) in Small Wounds in Healthy Male Subjects

Primary Purpose

Cicatrix, Wound Healing

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

Intradermal avotermin

Placebo (vehicle)

Placebo

About this trial

This is an interventional prevention trial for Cicatrix focused on measuring Cicatrix, Scar, Avotermin, Juvista, RN1001, TGF beta 3

Eligibility Criteria

18 Years - 45 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

Healthy, Caucasian, male subjects aged 18-45 years inclusive.
Weight between 60-100 kg and a BMI within the permitted range for their height using Quetelet's index - weight (kg)/height²(m). The permitted index is between 18-28.
Non-smokers, or ex-smokers that have not smoked for at least 3 months prior to screening.

Exclusion Criteria:

Subjects who have history or evidence of hypertrophic or keloid scarring or with tattoos or previous scars in the area to be biopsied.
Afro-Caribbean subjects are excluded because of the increased susceptibility to hypertrophic and keloid scarring.
Subjects who have evidence of any past or present clinically significant disease, particularly coagulation disorders, immuno-mediated conditions and skin diseases and allergies, such as clinically significant eczema.
Subjects with a history of clinically significant allergies, especially drug hypersensitivity to lignocaine or allergy to surgical dressings to be used in this trial.
Subjects with any clinically significant abnormality following review of pre-trial laboratory data and physical examination.
Subjects who are taking, or have taken, certain prescribed or investigational drugs in the three weeks prior to Day 0 and in particular topical or systemic steroids, anti-inflammatory and anti-coagulant drugs. Certain drugs are not excluded in this trial. These include OTC analgesics including paracetamol and codeine, vitamin and mineral supplements and OTC cold remedies.
Subjects who drink more than 28 units of alcohol per week (1 unit = 1/2 pint of beer (285mls) or 25ml of spirits or 1 glass of wine).
Subjects who have evidence of drug abuse.
Subjects who are known to have or had serum hepatitis or who are carriers of the hepatitis B surface antigen or hepatitis C antibody. Subjects with previous vaccination against Hepatitis B are not excluded per se.
Subjects who are known to have or had serum hepatitis or who are carriers of the hepatitis B core antibody and who show less than 10 units per litre of Anti-HBs.
Subjects who have previously had a positive result to the test for HIV antibodies, or who admit to belonging to a high risk group.
In the opinion of the investigator, a subject who is not likely to complete the trial for what ever reason.

Sites / Locations

Renovo Ltd

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Intradermal avotermin

Placebo (vehicle)

Arm Description

Outcomes

Primary Outcome Measures

To investigate genomic expression profiles after exposure to either intradermal avotermin (Juvista) or placebo

To investigate the genomic expression profiles of reduced scarring in healthy male volunteers

Secondary Outcome Measures

To collect further safety and toleration data for intradermal RN1001

To assess systemic exposure following intradermal RN1001 before and after minor skin incisions

To confirm accelerated healing associated with intradermal RN1001

To investigate how to power a genomic analysis study optimally for the detection of gene expression profiles associated with accelerated healing, drug delivery and improved scarring.

Full Information

NCT ID

NCT00977951

First Posted

September 15, 2009

Last Updated

September 15, 2009

Sponsor

Renovo

1. Study Identification

Unique Protocol Identification Number

NCT00977951

Brief Title

Genomic Changes Associated With the Use of Intradermal Avotermin (Juvista) in Small Wounds in Healthy Male Subjects

Official Title

A Single Centre, Double-blind, Methodology Trial to Investigate the Genomic Changes Associated With Accelerated Healing and Reduced Scarring of Small Wounds Using RN1001 in Healthy Male Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

September 2009

Overall Recruitment Status

Completed

Study Start Date

September 2002 (undefined)

Primary Completion Date

September 2003 (Actual)

Study Completion Date

September 2003 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Renovo

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to further determine the safety and toleration of intradermal avotermin (Juvista), confirm accelerated healing and investigate genomic expression profiles

Detailed Description

Subjects were allocated to two groups. Group 1 had scheduled visits on Day 0, 1, 3 and 4 while group 2 were scheduled for Day 0, 1, 5 and 6. Follow-up post-trial safety assessments were made on Day 10-20. On Day 0 each subject received a total of four 1cm incision wounds; two each to the upper, inner aspect of each arm. Two areas for incision were marked out on the inner aspect of each upper arm and anaesthetised before intradermal injection of Juvista or placebo. One incision site on each arm received a dose of 50ng/100μl Juvista and the other incision site received Placebo. Following injection a full thickness 1cm incision was made along the marked site. On Day 1 all subjects were re-injected with the same dose of Juvista or placebo, 100μl to each wound margin (200μl per wound site). On Day 3 subjects in Group 1 were re-dosed with 200μl Juvista or Placebo per site (100μl per linear cm approximated wound margin) in Arm 1. These sites were then excised with an elliptical excision. On Day 4 the same subjects received another dose of Juvista or placebo as before. Subjects in group 2 received the same treatment to their Arm 1 as those in group 1, except on Day 5 and 6. All wounds were monitored and photographed at two monthly intervals over the course of 6 months. At month 6, all incision sites on Arm 2 for both groups were excised. All excised wounds were snap frozen for genomic analysis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cicatrix, Wound Healing

Keywords

Cicatrix, Scar, Avotermin, Juvista, RN1001, TGF beta 3

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intradermal avotermin

Arm Type

Experimental

Arm Title

Placebo (vehicle)

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Intradermal avotermin

Other Intervention Name(s)

Juvista, RN1001, TGF beta 3

Intervention Description

50 ng/100 ul avotermin administered intradermally prior to wounding (day 0) and again 24 h later on day 1. Wounds were dosed again prior to wound excision on day 3 and again on day 4

Intervention Type

Drug

Intervention Name(s)

Intradermal avotermin

Other Intervention Name(s)

Juvista, RN1001, TGF beta 3

Intervention Description

50 ng/100 ul avotermin administered intradermally prior to wounding (day 0) and again 24 h later on day 1. Wounds were dosed again prior to wound excision on day 5 and again on day 6

Intervention Type

Drug

Intervention Name(s)

Placebo (vehicle)

Intervention Description

Placebo administered intradermally prior to wounding (day 0) and again 24 h later on day 1. Wounds were dosed again prior to wound excision on day 3 and again on day 4

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

50 ng/100 ul avotermin administered intradermally prior to wounding (day 0) and again 24 h later on day 1. Wounds were dosed again prior to wound excision on day 5 and again on day 6

Primary Outcome Measure Information:

Title

To investigate genomic expression profiles after exposure to either intradermal avotermin (Juvista) or placebo

Time Frame

Days 3 and 5

Title

To investigate the genomic expression profiles of reduced scarring in healthy male volunteers

Time Frame

Days 3 and 5 and month 6

Secondary Outcome Measure Information:

Title

To collect further safety and toleration data for intradermal RN1001

Time Frame

Day 15 and month 6

Title

To assess systemic exposure following intradermal RN1001 before and after minor skin incisions

Time Frame

Day 15 and month 6

Title

To confirm accelerated healing associated with intradermal RN1001

Time Frame

Days 3 and 5

Title

To investigate how to power a genomic analysis study optimally for the detection of gene expression profiles associated with accelerated healing, drug delivery and improved scarring.

Time Frame

Days 3 and 5

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy, Caucasian, male subjects aged 18-45 years inclusive. Weight between 60-100 kg and a BMI within the permitted range for their height using Quetelet's index - weight (kg)/height²(m). The permitted index is between 18-28. Non-smokers, or ex-smokers that have not smoked for at least 3 months prior to screening. Exclusion Criteria: Subjects who have history or evidence of hypertrophic or keloid scarring or with tattoos or previous scars in the area to be biopsied. Afro-Caribbean subjects are excluded because of the increased susceptibility to hypertrophic and keloid scarring. Subjects who have evidence of any past or present clinically significant disease, particularly coagulation disorders, immuno-mediated conditions and skin diseases and allergies, such as clinically significant eczema. Subjects with a history of clinically significant allergies, especially drug hypersensitivity to lignocaine or allergy to surgical dressings to be used in this trial. Subjects with any clinically significant abnormality following review of pre-trial laboratory data and physical examination. Subjects who are taking, or have taken, certain prescribed or investigational drugs in the three weeks prior to Day 0 and in particular topical or systemic steroids, anti-inflammatory and anti-coagulant drugs. Certain drugs are not excluded in this trial. These include OTC analgesics including paracetamol and codeine, vitamin and mineral supplements and OTC cold remedies. Subjects who drink more than 28 units of alcohol per week (1 unit = 1/2 pint of beer (285mls) or 25ml of spirits or 1 glass of wine). Subjects who have evidence of drug abuse. Subjects who are known to have or had serum hepatitis or who are carriers of the hepatitis B surface antigen or hepatitis C antibody. Subjects with previous vaccination against Hepatitis B are not excluded per se. Subjects who are known to have or had serum hepatitis or who are carriers of the hepatitis B core antibody and who show less than 10 units per litre of Anti-HBs. Subjects who have previously had a positive result to the test for HIV antibodies, or who admit to belonging to a high risk group. In the opinion of the investigator, a subject who is not likely to complete the trial for what ever reason.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael J Davies

Organizational Affiliation

Renovo

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Jonathan Duncan

Organizational Affiliation

Renovo

Official's Role

Principal Investigator

Facility Information:

Facility Name

Renovo Ltd

City

Manchester

ZIP/Postal Code

M13 9XX

Country

United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Genomic Changes Associated With the Use of Intradermal Avotermin (Juvista) in Small Wounds in Healthy Male Subjects

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