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

This study has been completed.
Sponsor:
Information provided by:
Renovo
ClinicalTrials.gov Identifier:
NCT00984854
First received: September 24, 2009
Last updated: NA
Last verified: September 2009
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Cicatrix
Re-epithelialisation
Drug: Juvidex
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Renovo:

Primary Outcome Measures:
  • To assess the safety and local toleration of various dose levels of Juvidex (RN1004) injected intradermally in healthy volunteers. [ Time Frame: 22 Days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the systemic PK of various dose levels of Juvidex injected intradermally. [ Time Frame: 22 days ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • To find the maximum tolerated dose (MTD) of Juvidex [ Time Frame: 22 days ] [ Designated as safety issue: Yes ]

Enrollment: 70
Study Start Date: January 2004
Study Completion Date: July 2004
Primary Completion Date: July 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intradermal Juvidex Drug: Juvidex
Intradermal Juvidex, 100μl of 50mM (1.41mg/100μl) administered just prior to wounding and 200μl administered 24 h later
Other Names:
  • Mannose-6-phosphate
  • M6P
  • RN1004
Drug: Juvidex
Intradermal Juvidex, 100μl of 100mM (2.82mg/100μl) administered just prior to wounding and 200μl administered 24 h later
Other Names:
  • Mannose-6-phosphate
  • M6P
  • RN1004
Drug: Juvidex
Intradermal Juvidex, 100μl of 200mM (5.64mg/100μl) administered just prior to wounding and 200μl administered 24 h later
Other Names:
  • Mannose-6-phosphate
  • M6P
  • RN1004
Drug: Juvidex
Intradermal Juvidex, 100μl of 300mM (8.46mg/100μl) administered just prior to wounding and 200μl administered 24 h later
Other Names:
  • Mannose-6-phosphate
  • M6P
  • RN1004
Drug: Juvidex
Intradermal Juvidex, 100μl of 400mM (11.28mg/100μl) administered just prior to wounding and 200μl administered 24 h later
Other Names:
  • Mannose-6-phosphate
  • M6P
  • RN1004
Drug: Juvidex
Intradermal Juvidex, 100μl of 600mM (16.93mg/100μl) administered just prior to wounding and 200μl administered 24 h later
Other Names:
  • Mannose-6-phosphate
  • M6P
  • RN1004
Placebo Comparator: Placebo (vehicle) Drug: Placebo
Intradermal Placebo (0.9% phosphate buffered saline, pH 7.0), 100μl administered just prior to wounding and 200μl administered 24 later

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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  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: NCT00984854

Locations
United Kingdom
Renovo
Manchester, United Kingdom, M13 9XX
Sponsors and Collaborators
Renovo
Investigators
Principal Investigator: Jeremy Bond Renovo
Principal Investigator: Jonathan Duncan Renovo
  More Information

No publications provided

Responsible Party: John Hutchison, Medical Director, Renovo
ClinicalTrials.gov Identifier: NCT00984854     History of Changes
Other Study ID Numbers: RN1004-319-1001
Study First Received: September 24, 2009
Last Updated: September 24, 2009
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Renovo:
Cicatrix
Scar
Wound-healing
Re-epithelialisation
RN1004
Mannose-6-phosphate
M6P
Juvidex

Additional relevant MeSH terms:
Cicatrix
Fibrosis
Pathologic Processes

ClinicalTrials.gov processed this record on November 25, 2014