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Investigation Into the Safety of Intradermal Juvidex (M6P) Administered to Wounds of Healthy Subjects

Primary Purpose

Cicatrix, Re-epithelialisation

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Juvidex
Juvidex
Juvidex
Juvidex
Juvidex
Juvidex
Placebo
Sponsored by
Renovo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cicatrix focused on measuring Cicatrix, Scar, Wound-healing, Re-epithelialisation, RN1004, Mannose-6-phosphate, M6P, Juvidex

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Clinically healthy male and female subjects aged 18-45 years inclusive
  • Weight between 40 and 150kg and a BMI within the permitted range for their height using Quetelet's index - weight (kg)/height²(m). The permitted index is between 15 - 55 kg/m2

Exclusion Criteria:

  • Subjects who on direct questioning and physical examination have history or evidence of hypertrophic or keloid scarring or with tattoos or previous scars in the area to be biopsied
  • Subjects who have had surgery in the area to be biopsied within the previous 12 months
  • Afro-Caribbean subjects are excluded because of the 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, particularly coagulation disorders, diabetes, 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; or to any excipients or vehicle in the formulation or delivery vehicle
  • 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 drugs in the four weeks prior to Day 0 and in particular topical or systemic steroids, anti-inflammatory, anti-coagulant, antiproliferative drugs and antibiotics Certain drugs are not excluded in this trial, including OTC analgesics such as paracetamol and codeine, vitamin and mineral supplements and OTC cold remedies and hormonal contraceptives. If antibiotics are required after Day 0, this will not exclude subjects from continuation in this trial and the data will be recorded in the CRF
  • Subjects who have taken part in a clinical trial within 3 months prior to admission to this trial, or who are currently participating in a clinical trial, whether an investigational drug was involved or not
  • Subjects who have any clinical evidence of severe ongoing or prolonged depression or mental illness
  • Subjects who smoke more than 20 cigarettes a day
  • 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, (unless deemed NOT to be a hepatitis B carrier by the local Public Health laboratory)
  • Subjects who have previously had a positive result to the test for HIV antibodies, or who admit to belonging to a high-risk group
  • Subjects who are pregnant or planning to get pregnant or lactating or not taking adequate contraceptive precautions. Subjects must use suitable mechanical forms of contraception (or abstinence) during the trial
  • Subjects who are receiving the following drugs: cyclosporine, cyclophosphamide, taxol or warfarin
  • Subjects who have pre-existing clinically significant neurological conditions
  • In the opinion of the Investigator, a subject who is not likely to complete the trial for whatever reason

Sites / Locations

  • Renovo

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Intradermal Juvidex

Placebo (vehicle)

Arm Description

Outcomes

Primary Outcome Measures

To assess the safety and local toleration of various dose levels of Juvidex (RN1004) injected intradermally in healthy volunteers.

Secondary Outcome Measures

To determine the systemic PK of various dose levels of Juvidex injected intradermally.
To determine the histological effects on wound healing (re-epithelialisation, inflammatory cell infiltrate, angiogenesis and matrix deposition) of intradermal injections of Juvidex in healthy subjects.
To find the maximum tolerated dose (MTD) of Juvidex

Full Information

First Posted
September 24, 2009
Last Updated
September 24, 2009
Sponsor
Renovo
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1. Study Identification

Unique Protocol Identification Number
NCT00984854
Brief Title
Investigation Into the Safety of Intradermal Juvidex (M6P) Administered to Wounds of Healthy Subjects
Official Title
A Trial to Investigate the Clinical Safety, Local Toleration, and Systemic Pharmacokinetics of Repeated, Escalating Concentrations of Intradermal RN1004 to Wounds of Healthy Subjects.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2009
Overall Recruitment Status
Completed
Study Start Date
January 2004 (undefined)
Primary Completion Date
July 2004 (Actual)
Study Completion Date
July 2004 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Renovo

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study was to investigate the safety and toleration of various doses of intradermal Juvidex (mannose-6-phosphate) administered to punch biopsies of normal subjects.
Detailed Description
Each subject received a total of four wounds, two 3mm punch biopsies (at least 5cm apart) to the upper, inner aspect of each arm. Subjects served as their own control, i.e. one punch biopsy on Arm 1 received Juvidex and the other punch biopsy received Placebo or Standard Care. Arm 2 punch biopsies received the same treatments as for Arm 1 but in reverse, i.e. treatments were matched across the arms. On Day 0 the two areas for punch biopsies on Arm 1 were marked and anaesthetised and randomised to receive Juvidex or Placebo. Prior to wounding sites were injected intradermally with 100μl investigational product per site. Juvidex was dosed at 50, 100, 200, 300, 400, and 600mM. On Day 1 (24 h later) wounds were dosed as on Day 0 but with 200μl investigational product per site. On Day 3 the biopsy sites on Arm 1 were excised to determine re-epithelialisation. Arm 2 treatments and punch biopsies were carried out on Day 3, with further dosing 24 h later on Day 4 (as with Arm 1 wounding and treatments). These biopsy sites were excised on Day 8 of the study to obtain a 5 day-old wound. The randomisation of the treatment allowed for control of possible positional effects on healing. One subject in each group was randomised to receive only Placebo and Standard Care to their biopsy wounds.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cicatrix, Re-epithelialisation
Keywords
Cicatrix, Scar, Wound-healing, Re-epithelialisation, RN1004, Mannose-6-phosphate, M6P, Juvidex

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intradermal Juvidex
Arm Type
Experimental
Arm Title
Placebo (vehicle)
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Juvidex
Other Intervention Name(s)
Mannose-6-phosphate, M6P, RN1004
Intervention Description
Intradermal Juvidex, 100μl of 50mM (1.41mg/100μl) administered just prior to wounding and 200μl administered 24 h later
Intervention Type
Drug
Intervention Name(s)
Juvidex
Other Intervention Name(s)
Mannose-6-phosphate, M6P, RN1004
Intervention Description
Intradermal Juvidex, 100μl of 100mM (2.82mg/100μl) administered just prior to wounding and 200μl administered 24 h later
Intervention Type
Drug
Intervention Name(s)
Juvidex
Other Intervention Name(s)
Mannose-6-phosphate, M6P, RN1004
Intervention Description
Intradermal Juvidex, 100μl of 200mM (5.64mg/100μl) administered just prior to wounding and 200μl administered 24 h later
Intervention Type
Drug
Intervention Name(s)
Juvidex
Other Intervention Name(s)
Mannose-6-phosphate, M6P, RN1004
Intervention Description
Intradermal Juvidex, 100μl of 300mM (8.46mg/100μl) administered just prior to wounding and 200μl administered 24 h later
Intervention Type
Drug
Intervention Name(s)
Juvidex
Other Intervention Name(s)
Mannose-6-phosphate, M6P, RN1004
Intervention Description
Intradermal Juvidex, 100μl of 400mM (11.28mg/100μl) administered just prior to wounding and 200μl administered 24 h later
Intervention Type
Drug
Intervention Name(s)
Juvidex
Other Intervention Name(s)
Mannose-6-phosphate, M6P, RN1004
Intervention Description
Intradermal Juvidex, 100μl of 600mM (16.93mg/100μl) administered just prior to wounding and 200μl administered 24 h later
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Intradermal Placebo (0.9% phosphate buffered saline, pH 7.0), 100μl administered just prior to wounding and 200μl administered 24 later
Primary Outcome Measure Information:
Title
To assess the safety and local toleration of various dose levels of Juvidex (RN1004) injected intradermally in healthy volunteers.
Time Frame
22 Days
Secondary Outcome Measure Information:
Title
To determine the systemic PK of various dose levels of Juvidex injected intradermally.
Time Frame
22 days
Title
To determine the histological effects on wound healing (re-epithelialisation, inflammatory cell infiltrate, angiogenesis and matrix deposition) of intradermal injections of Juvidex in healthy subjects.
Time Frame
Day 3 and 5
Title
To find the maximum tolerated dose (MTD) of Juvidex
Time Frame
22 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Clinically healthy male and female subjects aged 18-45 years inclusive Weight between 40 and 150kg and a BMI within the permitted range for their height using Quetelet's index - weight (kg)/height²(m). The permitted index is between 15 - 55 kg/m2 Exclusion Criteria: Subjects who on direct questioning and physical examination have history or evidence of hypertrophic or keloid scarring or with tattoos or previous scars in the area to be biopsied Subjects who have had surgery in the area to be biopsied within the previous 12 months Afro-Caribbean subjects are excluded because of the 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, particularly coagulation disorders, diabetes, 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; or to any excipients or vehicle in the formulation or delivery vehicle 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 drugs in the four weeks prior to Day 0 and in particular topical or systemic steroids, anti-inflammatory, anti-coagulant, antiproliferative drugs and antibiotics Certain drugs are not excluded in this trial, including OTC analgesics such as paracetamol and codeine, vitamin and mineral supplements and OTC cold remedies and hormonal contraceptives. If antibiotics are required after Day 0, this will not exclude subjects from continuation in this trial and the data will be recorded in the CRF Subjects who have taken part in a clinical trial within 3 months prior to admission to this trial, or who are currently participating in a clinical trial, whether an investigational drug was involved or not Subjects who have any clinical evidence of severe ongoing or prolonged depression or mental illness Subjects who smoke more than 20 cigarettes a day 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, (unless deemed NOT to be a hepatitis B carrier by the local Public Health laboratory) Subjects who have previously had a positive result to the test for HIV antibodies, or who admit to belonging to a high-risk group Subjects who are pregnant or planning to get pregnant or lactating or not taking adequate contraceptive precautions. Subjects must use suitable mechanical forms of contraception (or abstinence) during the trial Subjects who are receiving the following drugs: cyclosporine, cyclophosphamide, taxol or warfarin Subjects who have pre-existing clinically significant neurological conditions In the opinion of the Investigator, a subject who is not likely to complete the trial for whatever reason
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeremy Bond
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
City
Manchester
ZIP/Postal Code
M13 9XX
Country
United Kingdom

12. IPD Sharing Statement

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Investigation Into the Safety of Intradermal Juvidex (M6P) Administered to Wounds of Healthy Subjects

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