Clinical trial NCT04877756: Study to Evaluate Efficacy of OLX10010 in Reducing Recurrence of Hypertrophic Scarring After Scar Revision Surgery
Official title: Phase 2a Prospective, Randomized, Double-blind, Intra-subject, Placebo-controlled, Proof of Concept Study to Evaluate the Efficacy of OLX10010 as an Adjunct Therapy to Reduce the Recurrence of Hypertrophic Scars After Scar Revision Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertrophic Scar
Keywords: scar revision surgery
OLX10010
siRNA
Lead sponsor: Olix Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Alira Health
First posted: 2021-05-07
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2 parallel arms and then a 3rd arm will be enrolled if the endpoints for the first 2 arms aren't met.
Primary purpose: PREVENTION

Brief summary: Phase 2a, prospective, randomized, double-blind, intra-subject, placebo-controlled, proof of concept study. Approximately twenty subjects will be randomized 1:1 to one of two treatment arms:

Arm A: 2.0 mg/cm OLX10010 biweekly (every two weeks) Arm B: 5.0 mg/cm OLX10010 biweekly (every two weeks) Each treatment arm will have approximately 10 subjects. Each subject will receive both active (OLX10010) and control (placebo) treatment post-hypertrophic scar surgery biweekly (every two weeks) for a total of six doses. Dosing will occur post-surgery on Weeks 2, 4, 6, 8, 10, and 12. Post-treatment follow-up visits will occur at Weeks 18 and 24, and a long-term follow-up visit will occur at Month 12. The Patient and Observer Scar Assessment Scale (both physician and patient scales), Stony Brook Scar Evaluation Scale, Vancouver Scar Scale, and a photograph-based visual analog scale by blinded experts will be completed prior to scar revision surgery, at Weeks 2, 8, 12, 18, and 24, and at Month 12. The overall opinion responses on the physician scales of the POSAS at Week 24 will be used for primary endpoint analysis.

The total length of the linear hypertrophic scar line will be divided equally for treatment with OLX10010 and placebo, injected intradermally per centimeter (cm). The OLX10010 end and placebo end of the scar line will be separated by a 2 cm or greater distance depending on the scar length.

After the Week 24 visit, all data collected will be cleaned and all data management activities will be completed. After the database is frozen/locked, the primary endpoint efficacy analysis will be completed. If at least one of the treatment arms are shown to be appropriate to reduce recurrence of hypertrophic scars, all analyses will be performed. If the efficacy analysis of Arms A and B indicate the study doses are not as effective as expected, the sponsor may decide to add a third arm (Arm C) to explore the weekly dosing regimen. See detailed summary.

Subjects in all study arms will continue in the study until their Month 12 visit. After all subjects complete that visit, data are collected, and data management activities are completed, Month 12 data will be analyzed.

Detailed description: This is a Phase 2a, prospective, randomized, double-blind, intra-subject, placebo-controlled, proof of concept study. Approximately twenty subjects will be randomized 1:1 to one of two treatment arms:

Arm A: 2.0 mg/cm OLX10010 biweekly (every two weeks) Arm B: 5.0 mg/cm OLX10010 biweekly (every two weeks) Each treatment arm will have approximately 10 subjects. Each subject will receive both active (OLX10010) and control (placebo) treatment post-hypertrophic scar surgery biweekly (every two weeks) for a total of six doses. Dosing will occur post-surgery on Weeks 2, 4, 6, 8, 10, and 12. Post-treatment follow-up visits will occur at Weeks 18 and 24, and a long-term follow-up visit will occur at Month 12. The Patient and Observer Scar Assessment Scale (both physician and patient scales), Stony Brook Scar Evaluation Scale, Vancouver Scar Scale, and a photograph-based visual analog scale by blinded experts will be completed prior to scar revision surgery, at Weeks 2, 8, 12, 18, and 24, and at Month 12. The overall opinion responses on the physician scales of the POSAS at Week 24 will be used for primary endpoint analysis.

The total length of the linear hypertrophic scar line will be divided equally for treatment with OLX10010 and placebo, injected intradermally per centimeter (cm). The OLX10010 end and placebo end of the scar line will be separated by a distance of 2 cm or greater depending on the scar length.

After the Week 24 visit, all data collected will be cleaned and all data management activities will be completed. After the database is frozen/locked, the primary endpoint efficacy analysis will be completed. If at least one of the treatment arms are shown to be appropriate to reduce recurrence of hypertrophic scars, all analyses will be performed. If the efficacy analysis of Arms A and B indicate the study doses are not as effective as expected, the sponsor may decide to add a third arm (Arm C) to explore the weekly dosing regimen:

Arm C: 2.0 mg/cm OLX10010 weekly If added, Arm C will enroll 10 subjects. Each subject will receive both active (OLX10010) and control (placebo) treatment post-hypertrophic scar surgery weekly for a total of 11 doses. Dosing will occur post-surgery on Weeks 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12. Post-treatment follow-up visits will occur on Weeks 18 and 24, and a long-term follow-up visit will occur at Month 12. The Patient and Observer Scar Assessment Scale (both physician and patient scales), Stony Brook Scar Evaluation Scale, Vancouver Scar Scale, and a photograph-based visual analog scale by two blinded independent assessors will be completed prior to scar revision surgery, at Weeks 2, 8, 12, 18, and 24, and at Month 12. The overall opinion responses on the physician scales of the POSAS at Week 24 will be used for primary endpoint analysis. After all subjects in Arm C complete Week 24, all data are collected, and all data management activities are completed, a new database freeze/lock will be performed. Arm C data will be analyzed.

Subjects in all study arms will continue in the study until their Month 12 visit. After all subjects complete that visit, data are collected, and data management activities are completed, Month 12 data will be analyzed.

Eligibility criteria: Inclusion Criteria:

* Healthy males or females, aged 18 to 65, inclusive
* Hypertrophic scar in the abdominal region, from previous surgery or injury, present for ≥ 12 months
* Linear hypertrophic scar equal to or greater than 8 cm in length
* Undergoing elective hypertrophic scar revision surgery
* Serum pregnancy test negative for females of childbearing potential
* Males and females of child-bearing potential (e.g., not post-menopausal for at least one year or surgically sterile) must agree to use effective contraception starting at the Screening Visit and continuing until 14 days after the last dose of OLX10010.
* Properly obtained written informed consent

Exclusion Criteria:

* BMI greater than 32 kg/m2. Exceptions to this criteria can be granted for patients just over this value per PI's discretion
* Hypertrophic scars outside the abdominal area, including face, neck, back, limbs, and the thoracic region
* Hypertrophic scar secondary to burns
* Active infection near the scar revision surgery
* Clinically significant wound near the scar revision surgery
* Additional scar(s) within 2 cm of the scar revision surgery
* End-stage renal disease or severe renal impairment as indicated by serum creatinine \> 2.5 mg/dL
* Tanning (natural or artificial) within 14 days prior to the screening visit or unwilling to abstain from natural or artificial tanning for four weeks after surgery. Tanning is not recommended for the remainder of the study but will not be an exclusion criteria or reason for early termination.
* Hypertrophic scar treatment within 12 weeks prior to the screening visit, excluding scar revision surgery
* Radiation or chemotherapy within 12 weeks prior to the screening visit
* Treatment with anti-psychotic, anti-cancer, immunosuppressant, or corticosteroids within 12 weeks prior to the screening visit
* Atopic dermatitis, keloid scar, or skin hypersensitivity
* Received elective body sculpting procedures (e.g., CoolSculpting®) for the abdomen within the past 6 months
* Use of tobacco or nicotine-containing products during study participation (Screening Visit through last follow-up visit)
* Female patients who are pregnant or breastfeeding
* Participation in any experimental drug or device study within 30 days prior to the screening visit
* Any clinically significant finding, in the judgement of the treating investigator, that would place the subject at health risk, impact the study, or affect the completion of the study.

Primary outcomes:
measure: • Change in recurrence of hypertrophic scar after scar revision surgery measured by physician scar assessment using the overall opinion score on the Observer Scar Assessment Scale at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: • Change in the recurrence of hypertrophic scar after scar revision surgery measured by patient scar assessment using the overall opinion score on the Patient Scar Assessment Scale at Week 24
timeFrame: Week 24
measure: • Recurrence of hypertrophic scar after scar revision surgery at Weeks 2, 8, 12, 18, and 24 and Month 12 according to Physician
timeFrame: Week 24 and Month 12
measure: • Recurrence of hypertrophic scar after scar revision surgery at Weeks 2, 8, 12, 18, and 24 and Month 12 according to Patient
timeFrame: Week 24 and Month 12
measure: • Scar severity
timeFrame: Week 24 and Month 12
measure: • Assessment of Blinded Photographs by Two Independent Assessors:
timeFrame: Week 24 and Month 12
measure: • Scar variations
timeFrame: Week 24 and Month 12
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: Week 24 and Month 12
measure: Severity of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: Week 24 and Month 12
Other outcomes:
Locations:
city: Washington
country: United States
facility: MedStar Health Research Institute
state: District of Columbia
city: Miami
country: United States
facility: Miami Dermatology & Laser Research, LLC
state: Florida
city: Miami
country: United States
facility: Miami Plastic Surgery
state: Florida
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Paddington Testing Co, Inc.
state: Pennsylvania
Study officials:
affiliation: OliX Pharmaceuticals
name: Alexander Neumeister, MD
role: STUDY_DIRECTOR
References:
citation: Hwang J, Chang C, Kim JH, Oh CT, Lee HN, Lee C, Oh D, Lee C, Kim B, Hong SW, Lee DK. Development of Cell-Penetrating Asymmetric Interfering RNA Targeting Connective Tissue Growth Factor. J Invest Dermatol. 2016 Nov;136(11):2305-2313. doi: 10.1016/j.jid.2016.06.626. Epub 2016 Jul 15.