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

This study has been completed.
Sponsor:
Information provided by:
Renovo
ClinicalTrials.gov Identifier:
NCT00978367
First received: September 15, 2009
Last updated: NA
Last verified: September 2009
History: No changes posted
  Purpose

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 Intervention Phase
Cicatrix
Wound Healing
Re-epithelialization
Drug: Avotermin
Drug: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:


Further study details as provided by Renovo:

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 [ Time Frame: Day 5 post surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the safety and toleration of various concentrations of avotermin (Juvista) applied by intradermal injection at various timepoints [ Time Frame: Days 0-14 post-wounding ] [ Designated as safety issue: Yes ]
  • To determine the systemic exposure of various concentrations of avotermin (Juvista) applied by intradermal injection at various timepoints [ Time Frame: Days 0-14 post-wounding ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: 0-6 months post-wounding ] [ Designated as safety issue: No ]
  • To determine the anti-scarring potential of two doses of avotermin (Juvista) when applied by intradermal injection at various dosing frequencies [ Time Frame: Day 5 and 6 months post-wounding ] [ Designated as safety issue: No ]

Enrollment: 43
Study Start Date: February 2002
Study Completion Date: November 2002
Primary Completion Date: November 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00978367

Locations
United Kingdom
Renovo Ltd
Manchester, United Kingdom, M13 9XX
Sponsors and Collaborators
Renovo
Investigators
Principal Investigator: Michael J Davies Renovo
Principal Investigator: Jonathan Duncan Renovo
  More Information

No publications provided

Responsible Party: John Hutchison, Medical Director, Renovo Ltd
ClinicalTrials.gov Identifier: NCT00978367     History of Changes
Other Study ID Numbers: RN1001-319-1003
Study First Received: September 15, 2009
Last Updated: September 15, 2009
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Renovo:
Cicatrix
Scar
Avotermin
Juvista
RN1001
TGF beta 3

Additional relevant MeSH terms:
Cicatrix
Fibrosis
Pathologic Processes

ClinicalTrials.gov processed this record on July 24, 2014