Anti-Scarring Efficacy and Safety of Intradermal Juvista (Avotermin) in Healthy Males

A Single-Site, Double-Blind, Phase II Trial to Investigate the Safety, Toleration, Systemic Exposure and Anti-Scarring Potential of Different Applications of Intradermal Juvista (Avotermin) in Male Subjects Aged 18-45 Years

This study was undertaken to investigate safety and scar-improvement activity of different applications of Juvista (avotermin), administered to surgical incisions made to the skin of a healthy population of male volunteers aged 18-45 years. The study addressed two issues: whether Juvista (avotermin) administered at 200ng/100μl/linear cm wound margin is more effective than 50ng/100μl/linear cm for scar improvement and, secondly, whether dosing once only (before wounding) or twice (before and after wounding) is optimal for scar improvement.

Study Overview

• Status: Completed
• Conditions: Cicatrix
• Intervention / Treatment: Drug: Juvista (avotermin) plus placebo, standard-care (within-subject controls)

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • La
    • Manchester, La, United Kingdom, M13 9XX
      • Clinical Trials Unit, Renovo Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Clinically healthy, male subjects aged 18 to 45 years (inclusive)
• Body weight between 40kg and 150kg or a body mass index within the range 15-55kg/m2, calculated using Quetelet's index

Exclusion Criteria:

• Subjects with history or evidence of hypertrophic or keloid scarring, or with tattoos or previous scars in the area to be biopsied.
• Subjects with tattoos or previous scars within 3cm of the area to be incised during the trial.
• Afro-Caribbean volunteers, because of their increased susceptibility to hypertrophic and keloid scarring.
• Subjects who, on direct questioning and physical examination, have evidence of any past or present clinically significant disease.
• Subjects with a chronic or currently active skin disorder, which would adversely affect the healing of the acute wounds or involved the areas to be examined in this trial.
• Subjects with a history of clinically significant allergies.
• Subjects with any clinically significant abnormality following review of pre-trial laboratory data and physical examination.
• Subjects taking, or who had taken, certain prescribed drugs in the 4 weeks before to Day 0 and, in particular, topical or systemic steroids, anti-inflammatory, anti-coagulant, anti-proliferative drugs, and antibiotics.
• Subjects who have taken part in a clinical trial within 3 months before admission to this trial, or who are currently participating in a clinical trial, whether an investigational drug was involved or not.
• Subjects with any clinical evidence of severe ongoing, or prolonged, depression or mental illness.
• Subjects smoking more than 20 cigarettes a day.
• Subjects drinking more than 28 units of alcohol per week (1 unit = ½ pint of beer [285ml], 25ml of spirits, or 1 glass of wine).
• Subjects showing evidence of drug abuse.
• Subjects known to have, or to have had, serum hepatitis or who were carriers of the hepatitis B surface antigen (HbsAg) or hepatitis C antibody.
• Subjects previously testing positive for HIV antibodies, or who admit to belonging to a high-risk group.
• Subjects with pre-existing clinically significant neurological conditions.
• Subjects who, in the opinion of an investigator, are not likely to complete the trial for whatever reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; Juvista (avotermin) 50ng/100μl/linear cm wound margin	Drug: Juvista (avotermin) plus placebo, standard-care (within-subject controls); Intradermal Juvista (avotermin) at 50ng or 200ng per 100μl per linear cm of wound margin; Other Names: RN1001; Juvista; Avotermin
Active Comparator: 2; Juvista (avotermin) at 200ng/100μl/linear cm	Drug: Juvista (avotermin) plus placebo, standard-care (within-subject controls); Intradermal Juvista (avotermin) at 50ng or 200ng per 100μl per linear cm of wound margin; Other Names: RN1001; Juvista; Avotermin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Scar appearance	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety: adverse events, local tolerability, systemic exposure	12 months

Collaborators and Investigators

• Sponsor: Renovo
• Investigators: Principal Investigator: Jim Bush, MBChB, Renovo Ltd

Publications and helpful links

General Publications

• Bush J, Duncan JAL, Bond JS, Durani P, So K, Mason T, O'Kane S, Ferguson MWJ. Scar-improving efficacy of avotermin administered into the wound margins of skin incisions as evaluated by a randomized, double-blind, placebo-controlled, phase II clinical trial. Plast Reconstr Surg. 2010 Nov;126(5):1604-1615. doi: 10.1097/PRS.0b013e3181ef8e66.

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Study Completion (Actual): March 1, 2005

Study Registration Dates

• First Submitted: December 11, 2007
• First Submitted That Met QC Criteria: January 2, 2008
• First Posted (Estimate): January 15, 2008

Study Record Updates

• Last Update Posted (Estimate): January 15, 2008
• Last Update Submitted That Met QC Criteria: January 2, 2008
• Last Verified: January 1, 2008

More Information

Terms related to this study

• Keywords: cicatrix, scarring, TGF-beta3, avotermin, Juvista
• Additional Relevant MeSH Terms: Pathologic Processes; Fibrosis; Cicatrix
• Other Study ID Numbers: RN1001-319-1011