Clinical trial NCT04186273: Clinical Safety and Scar Prevention Study of a Topical Antifibrotic Compound FS2.
Official title: Post-operative Topical Administration of Fibrosis Inhibiting Compound FS2 in a Double-blind, Randomized, Vehicle-controlled Study Evaluating the Safety and Prevention of Cutaneous Scarring in Skin Grafts and Donor Sites.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Scar
Cicatrix
Hypertrophic Scar
Skin Graft Scar
Skin Graft Complications
Donor Site Complication
Keloid
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2019-12-04
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: QUADRUPLE-BLINDED, RANDOMIZED, VEHICLE-CONTROLLED STUDY INTRA-SUBJECT CONTROLS
Primary purpose: PREVENTION

Brief summary: The study will investigate the safety and effectiveness of daily post surgical scar management, using a moisture-balancing base product containing different amounts of a novel (NCE) antifibrogenic compound FS2, a natural metabolite of the kynurenine pathway. Results of recent peer-reviewed, pre-clinical evidence warrant further investigation to validate therapeutic scar preventive efficacy of topically administered/delivered FS2. There are no known safety concerns with current product formulations. Recent Phase I clinical safety and tolerability data further support continuation of the research proposed in this study.

Detailed description: Study Arms (Investigational Conditions):

Total of 6, categorized by type of wound and treatment allocation.

Description of Study Arms:

The quality of tissue repair and scarring will be evaluated in two different, bisected post-surgical sites on the same Participant. Each wound site represents a Study Arm. Each wound site will receive two treatments, one of which is always a vehicle. In total the two wound types provide a total of 6 Study Arms for statistical analysis.

Arm 1 / Wound Type 1 (skin grafted wounds: 3-treatment groups): The wound site (injury) that requires skin grafting surgery to remove normal, uninjured skin from the same Participant to cover and repair a deep wound (a "skin graft").

Arm 2 / Wound Type (donor skin graft harvest site; 3-treatment groups): A surgical wound where a piece of normal skin is removed at uniform depth using a dermatome to harvest a skin graft ("skin graft harvest site").

The bisected wound site is randomly assigned either a control or FS2 cream treatment.

Treatment Groups: Each wound site will be used to investigate and compare three different treatments. Participants will apply the investigated treatments ("IP") as directed to allocated bisected sections of the skin grafted wound and donor wound site for 90 days. Follow-on assessments will be conducted with additional study visits on Days 180 and 270 (study endpoint).

There are four (4) differently labelled products as follows:

Treatment-1 (IP1) A single, daily application of a moisturizing cream-base.

Treatment-2 (IP2) A single, daily application of a moisturizing cream-base with FS2 (0.50% w/w).

Treatment-3 (IP3) A single, daily application of a moisturizing cream-base with FS2 (0.25% w/w). IP3 will have two different product labels to conceal the identity of the vehicle.

Control-cream (IP1), and treatments IP2 and IP3 each containing 0.50%w/w or 0.25%w/w FS2 respectively, will be topically applied to designated treatment sites once per day for a period of 90 days. Investigator and participant will be blinded from both identity of treatment product and randomized location. Each participant will be provided a different cream for each bisected-site for a total of four (4) differently labelled creams; two for the donor site, and two for the skin grafted site. Participants will discuss and be informed/reminded at each visit about study design, responsibilities, possible adverse events, proper daily wound care and cream application methods.

Eligibility criteria: Inclusion Criteria:

1. Medically able to consent to study requirements
2. Adult, male and female trauma patients
3. Ages 18 to 65 years of age
4. Fluent in English (able to consent without a translator)
5. Isolated skin wound of 3% Total Body Surface Area
6. Participant requires partial thickness skin graft (meshed/non-meshed), face and genitalia excluded.
7. Grafted skin is between 100 cm2 and 600 cm2
8. Maximum skin graft expansion ratio is 1:1.5

Exclusion Criteria:

1. Medically unable to consent to study requirements
2. Require an English translator to lawfully consent to the study and its requirements
3. Treatment sights (skin graft sights) located on the face and genitalia
4. Expected to be medically unstable for the duration of the study period and an additional 1-month thereafter
5. Pregnant, or attempting to become pregnant
6. Known immunosuppression or immunosuppressive illness
7. Subjects who had 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 used or not.
8. Subjects who had any clinical evidence of severe ongoing or prolonged depression or mental illness
9. Subjects who smoke more than 20 cigarettes a day
10. Subjects who demonstrated evidence of drug abuse
11. Any other diagnosis, condition, physical or geographical limitation with the participant that may render, or increases the likelihood of rendering, him/her unable to complete the entire study.

Primary outcomes:
measure: Vancouver Scar Scale (VSS)
timeFrame: 0-9 months
measure: Patient and Observer Scar Assessment Scale (POSAS)
timeFrame: 0-9 months
Secondary outcomes:
measure: Adverse Events
timeFrame: 0-9 months
measure: Vital Signs - systolic blood pressure
timeFrame: 0-9 months
measure: Vital Signs - diastolic blood pressure
timeFrame: 0-9 months
measure: Vital Signs - Heart Rate
timeFrame: 0-9 months
measure: Vital Signs - Respiratory Rate
timeFrame: 0-9 months
measure: Vital Signs - Oral Temperature
timeFrame: 0-9 months
measure: Physical Exam Findings
timeFrame: 0-9 months
measure: Clinical Chemistry Results
timeFrame: 0-9 months
measure: Hematology Results
timeFrame: 0-9 months
measure: Urine Analysis Results
timeFrame: 0-9 months
measure: FS2 Pharmacokinetic urine analysis data
timeFrame: 0-2 hours; 0-9 months
measure: FS2 Pharmacokinetic blood analysis data
timeFrame: 0-2 hours; 0-9 months
measure: Pain Management
timeFrame: 0-9months
measure: Histology (Tissue Biopsies)
timeFrame: 3 months and 9 months
measure: Histology (Tissue Biopsies)
timeFrame: 3 months and 9 months
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: VGH Burn Unit
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Anthony Papp, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Papp A, Hartwell R, Evans M, Ghahary A. The Safety and Tolerability of Topically Delivered Kynurenic Acid in Humans. A Phase 1 Randomized Double-Blind Clinical Trial. J Pharm Sci. 2018 Jun;107(6):1572-1576. doi: 10.1016/j.xphs.2018.01.023. Epub 2018 Feb 6.