siRNA Microneedle Patches for Ear Keloid Post-Surgical Scars

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• Keloid 138
• Cicatrix 611

Keywords

• keloid
• microneedles
• scars
• small intefering RNA
• RNA
• ear
• earlobe

Keloid

138 studies on the registry are indexed under Keloid; 26 are open to participants now.

This study's planned enrollment of 158 is above the median of 30 across 109 interventional studies indexed under Keloid.

Lead sponsor

This is the only study on the registry with Ong Kim Yao as lead sponsor.

Study arms

• Active comparator
  CO2 laser surgery followed by intralesional steroid injection

  In the active comparator arm, participants are first treated with CO2 laser surgery of the ear keloid. The first dose of intralesional steroid injection is given immediately to the wound bed post-surgery, followed by subsequent doses of intralesional steroid injection administered at monthly intervals for four doses in total.

  Procedure: Carbon Dioxide (CO2) Laser Surgery · Drug: Intralesional Triamcinolone 40 mg/mL

• Experimental
  CO2 laser surgery followed by intralesional steroids and siRNA microneedle patches

  In the experimental arm, participants are first treated with CO2 laser surgery of the ear keloid. The first dose of intralesional steroid injection is given immediately to the wound bed post-surgery, followed by subsequent doses of intralesional steroid injection administered at monthly intervals for four doses in total. In addition, participants will apply siRNA microneedle patches for 10 hours per day for 90 days in total except on days where intralesional steroid injection is given to permit healing at puncture site.

  Drug: Small interfering RNA (siRNA) Microneedle Patches · Procedure: Carbon Dioxide (CO2) Laser Surgery · Drug: Intralesional Triamcinolone 40 mg/mL

Interventions

• DrugSmall interfering RNA (siRNA) Microneedle Patches

  Silencing or small interfering RNA (siRNA) are used to alter the expression of transforming growth factor secreted protein acidic and cysteine-rich (SPARC), a key mediator of wound fibrosis and keloid scar formation. Conjugating siRNA targeting SPARC mRNA with tyramine-modified gelatin to form a positively-charged nanoplex can help to enable siRNA protection against rapid in-vivo degradation, promoting uptake into fibroblasts via endocytosis, and enhacing targeted cellular delivery of the siRNA. These siRNA nanoplexes targeting SPARC mRNA are embedded in the tips of hyaluronic acid dissolvable microneedles (siRNA microneedles) to enhance transcutaneous drug delivery. In this study, participants in the experimental arm will apply siRNA microneedle patches daily for 10 hours a day in between monthly doses of intralesional corticosteroid injection for 90 days in total.

• ProcedureCarbon Dioxide (CO2) Laser Surgery

  Carbon Dioxide (CO2) laser ablation of the ear keloid will be performed, followed by intralesional corticosteroid injections alone (active comparator arm) or with siRNA microneedle patches (experimental arm)

• DrugIntralesional Triamcinolone 40 mg/mL

  Intralesional triamcinolone 40mg/ml injection. The first dose is given immediately to the wound bed post-surgery, then at monthly intervals for four doses in total.

Primary outcomes

1. Post-surgical scar appearance measured using the Vancouver Scar Scale (VSS) score

   The Vancouver Scar Scale (VSS) is a validated clinician-reported instrument that is a measure of scar severity comprising 4 domains assessing scar appearance and physical characteristics. The scale evaluates Vascularity (from 0 to 3), Pigmentation (from 0 to 2), Pliability (from 0 to 5) and Height (from 0 to 3). Each domain is assigned an individual score and combined to provide a total scar severity score ranging from 0 to 13, with higher values representing greater scar severity and poorer scar appearance. Changes in score over time may be used to assess response to treatment, with reductions in score representing clinical improvement. Score at baseline (post-surgical scar immediately post CO2 laser surgery) and at each review visit will be compared.

   Time frame: Visits at Day 0 (CO2 laser surgery), Day 15, Day 30, Day 60, Day 90, Day 120, Day 180, Day 270, Day 360 (through study completion)

2. Post-surgical scar appearance measured using Scar Cosmesis Assessment and Rating (SCAR) scale

   The Scar Cosmesis Assessment and Rating (SCAR) scale is a validated clinician-reported instrument that is a measure of post-surgical scar quality comprising multiple domains assessing scar appearance, symptoms, and overall cosmetic outcome. The scale evaluates Scar Spread (from 0 to 4), Erythema (from 0 to 3), Dyspigmentation (from 0 to 2), Track or suture marks (from 0 to 1), Hypertrophy or atrophy (from 0 to 3), Overall impression (from 0 to 1), and patient rated bothersome itch and pain over the preceding 24 hours (Yes or No). Individual domain scores are combined to provide a total assessment of scar severity and cosmesis, with higher values representing poorer scar appearance and greater symptom burden. Changes in score over time may be used to assess response to treatment, with reductions in score representing clinical improvement. Score at baseline (post-surgical scar immediately post CO2 laser surgery) and at each review visit will be compared.

   Time frame: Visits at Day 0 (CO2 laser surgery), Day 15, Day 30, Day 60, Day 90, Day 120, Day 180, Day 270, Day 360 (through study completion)

Secondary outcomes

1. Change from baseline on the Detroit Keloid Scale

   The Detroit Keloid Scale (DKS) is a validated, clinician- and patient-reported instrument to assess the severity and treatment response of keloids. It is designed specifically for keloid scars and evaluates both objective scar characteristics and patient symptoms. The DKS has two components - the Observer Keloid Assessment (clinician-reported domains of location, height and surface area) and Patient Keloid Questionnaire (patient-reported domains of pruritus, pain, contracture/limitation to range of motion and quality of life). Scores from each domain are combined to provide a total assessment of keloid severity, with higher values representing greater disease severity and symptom burden. Changes in score over time may be used to assess response to treatment, with reductions in score representing clinical improvement. Score at baseline and at each review visit will be compared.

   Time frame: Visits at Recruitment (before treatment), Day 0 (CO2 laser surgery), Day 15, Day 30, Day 60, Day 90, Day 120, Day 180, Day 270, Day 360 (through study completion)

2. Presence of recurrence

   Keloid recurrence will be defined by Height score of at least 1 on the Observer Keloid Assessment of the DKS. The keloid wound bed will be flat post-CO2 laser surgery and increase in height is taken to be an early marker of keloid recurrence.

   Time frame: At first detection of recurrence on any review visits (up to 1 year follow up, through study completion)

3. Recurrence rate

   The recurrence rate in each arm will be measured. It is calculated as the number of patients with keloid recurrence divided by the total number of patients in the treatment arm.

   Time frame: At first detection of recurrence on any review visits (up to 1 year follow up, through study completion)

4. Time to recurrence (for patients with ear keloid recurrence)

   For patients with recurrent ear keloid, time to ear keloid recurrence will be measured. It is calculated as the time from CO2 laser surgery (denoted as day 0) to time of first detection of keloid recurrence in days.

   Time frame: From day of CO2 laser surgery to day of first detection of keloid recurrence (up to 1 year follow up, through study completion)

5. Secondary rescue treatment (for patients with ear keloid recurrence)

   For patients with recurrent ear keloid, secondary rescue treatment will be measured in terms of treatment modality offered (such as repeat CO2 laser surgery, intralesional steroid injection) and response (resolution, partial response, no response).

   Time frame: Visits at Day 15, Day 30, Day 60, Day 90, Day 120, Day 180, Day 270, Day 360 visits, starting from first detection of recurrence (through study completion)

6. Patient-reported usability of siRNA microneedle patches (for patients in experimental arm only)

   Patients in the experimental arm who will receive the siRNA microneedle patches will fill in a questionnaire on the usability of the siRNA microneedle patches. The questionnaire evaluates 1) degree of acceptability of microneedle patches (four options of very acceptable, acceptable fair or not acceptable), 2) whether patients will use the microneedles patch again in the future to treat any future post-surgcial scars (Yes/No response, with further open ended elaboration), and 3) areas of improvement to suggest if any (optional open ended).

   Time frame: Visits at Day 60, Day 90, Day 120 (review visits while patients in experimental arm are being treated with microneedle patches)

7. Adverse effects

   Patients will be monitored for any adverse effects from the CO2 laser surgery, intralesional corticosteroid injections and/or the siRNA microneedle patches, such as but not limited to - dyspigmentation, skin atrophy, telangiectasia, edema, infection, contact dermatitis, ulceration, necrosis.

   Time frame: Visits at Day 0 (CO2 laser surgery), Day 15, Day 30, Day 60, Day 90, Day 120, Day 180, Day 270, Day 360 (through study completion)

Individual participant data

Plan to share: Yes

Supporting information: Study protocol, Statistical analysis plan

Time frame: De-identified individual participant data will be made available beginning 12 months following publication of the primary study results and ending 3 years thereafter.

Access criteria: Access to de-identified individual participant data may be granted to qualified researchers for scientifically sound research proposals approved by the study investigators and sponsoring institution. Requests must include a research proposal and statistical analysis plan. Data sharing is subject to applicable institutional, ethical, and regulatory approvals, and a signed data sharing agreement may be required prior to release of data. Data will be provided in a de-identified format through secure institutional channels upon approval of request.