Study to Assess Efficacy and Safety of Dupilumab in the Treatment of Keloids
An Open-label Proof of Concept Study Regarding the Efficacy and Safety of Dupilumab in the Treatment of Keloids
Study Overview
Detailed Description
Current scar treatments have limited efficacy and are often unsatisfactory although over $20 billion dollars are spent annually on the treatment and management of scars. Keloids, an abnormal proliferation of scar tissue, can be disfiguring, functionally impairing, and have dramatic impacts on quality of life. Treatments of keloids include a variety of modalities (i.e. intralesional steroid injections, silicone gel or sheets, surgery, laser, radiation therapy, cryotherapy, topical imiquimod, and intralesional 5-fluorouracil injections). However, current treatments are limited to primarily localized interventions.
The Investigators hypothesize that dupilumab can decrease the size and symptoms of keloids and improve patient's quality of life. An open-label proof of concept study regarding the use of dupilumab in patients with keloids may be the first step in elucidating a novel systematic approach to treatment of keloids.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Men and women between the ages of 18 and 65 at the time of dupilumab initiation.
- Subjects must have either one keloid with ≥ 2 cm length-wise or at least two keloids with ≥ 0.4 cm (width) x 0.4 cm (length)
- Subjects must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study related activity is performed.
Exclusion Criteria:
- History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis (Tb) infection as defined by a positive QuantiFERON TB-Gold test at screening.
- Known infection with HIV, hepatitis B or hepatitis C at screening.
- Are currently pregnant, breastfeeding, or planning to get pregnant during the study.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unwilling to use effective contraception during the study and for 8 weeks after stopping treatment. Methods of acceptable birth control are listed below under "Women of Childbearing Potential"
- Previous hypersensitivity reaction to dupilumab.
- Patients with acute asthma, acute bronchospasm or status asthmaticus.
- Patients with known helminth infections.
- Currently on any other immunosuppressant systemic medication or within 28 days of baseline visit.
- Underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the opinion of the investigator significantly immunocompromises the subject and/or places the subject at unacceptable risk for receiving an immunomodulatory therapy.
- Are participating in another study using an investigational agent or procedure during participation in this study or within 28 days prior to baseline visit.
- Any other treatment for keloids with 28 days prior to baseline visit, including silicone gel/sheets, laser therapy, intralesional steroid or 5-fluorouracil injections, topical steroid, cryotherapy, surgery, or radiation therapy.
- Has had a live vaccine
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: Dupilumab Subcutaneous Injection
600 mg at initial visit and 300mg every 2 weeks until week 22 Each subject will receive 600mg of Dupilumab at baseline visit and 300mg of Dupilumab as a subcutaneous injection every 2 weeks for a total of 9 doses over 22 weeks. |
Dupilumab a human monoclonal antibody of the immunoglobulin G4 subclass that inhibits interleukin (IL)-4 and IL-13 signaling by specifically binding to the IL-4 receptor alpha subunit, which is shared by the IL-4 and IL-13 receptor complexes.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Median Score of Patient and Observer Scar Assessment Scale (POSAS) From Baseline to Week 24
Time Frame: Baseline and Week 24
|
The POSAS measures scar quality by evaluating visual (e.g. color), tactile (e.g. pliability) and sensory (e.g. itch) characteristics of the scar from the perspective of the observer (investigator) and patients. POSAS is comprised of two numeric scales:
Both scales contain six items that are scored numerically on a 1-10 scale which are added for a total score. The PSAS score (range of 6-60) and OSAS score (range of 6-60) are combined to get a total scoring index (range of 12-120). Higher score = worse scar and lower score = better scar (closer to normal skin). |
Baseline and Week 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Vancouver Scar Scale (VSS).
Time Frame: Baseline and Week 24
|
Average score of patients for Vancouver Scar Scale (VSS) from baseline and week 24. Score Description: The VSS measures four parameters of scars: vascularity, pigmentation, pliability, and height. Each parameter contained ranked subscales that may be summed to obtain a total score ranging from 0 (representing normal skin) to 13 (representing worst scar imaginable).
|
Baseline and Week 24
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Dermatology Life Quality Index (DLQI).
Time Frame: Baseline and Week 24
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Average score patient-reported outcomes based on Dermatology Life Quality Index (DLQI). The DLQI is a validated general dermatology questionnaire that consists of 10 items that assess subject health-related quality of life (daily activities, personal relationships, symptoms and feelings, leisure, work and school, and treatment). The scoring of each question is as follows: Very much scored = 3 points, A lot scored = 2 points, A little scored = 1, Not at all scored = 0 points, Not relevant scored = 0 points, Question 7, 'prevented work or studying' scored = 3 points. The DLQI is calculated by adding the score of each question, resulting in a maximum of 30 (meaning maximum impact on quality of life) and a minimum of 0 (meaning no impact of skin disease on quality of life). The higher the score, the more quality of life is impaired. 0-1 = No effect on patient's life |
Baseline and Week 24
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Histology
Time Frame: Baseline and Week 24
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Histology Description: To determine the effects of dupilumab on Th2 pathway molecules (IL-4 and IL-13) and selected indicators and mediators of fibrosis in keloid tissue. Tissue was collected by skin biopsy during the baseline visit (pre-intervention) and Week 24 (post-intervention). Average of the markers at Baseline and Week 24 were analyzed to determine effect. Immunohistochemical staining was performed for the following markers: collagen I (ThermoFisher, OB1310-01, 1:200), TGF-β (Abcam, ab215715, 1:200), HSP47(Santa Cruz, sc-5293, 1:2000), αSMA (Sigma-Aldrich, A5228, 1:2000), and IL-4Ra (R&D Systems, MAB230, 0.5 ug/mL). Staining intensity or the percentage of positive cells was analyzed using ImageJ (National Institutes of Health, Bethesda, MD). |
Baseline and Week 24
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Mean Change in Volume of Keloid to Show Improvement
Time Frame: Baseline and Week 24
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Change in mean volume of keloid to show treatment response will be assessed based on photographs taken by Canfield camera analysis software for patients who have data for both baseline and week 24.
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Baseline and Week 24
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Histology - Tryptase
Time Frame: Baseline and Week 24
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Histology Description: To determine the effects of dupilumab on Th2 pathway molecules (IL-4 and IL-13) and selected indicators and mediators of fibrosis in keloid tissue. Tissue was collected by skin biopsy during the baseline visit (pre-intervention) and Week 24 (post-intervention). Average of the markers at Baseline and Week 24 were analyzed to determine effect. Immunohistochemical staining was performed for the following markers: mast cell tryptase (GeneTex - Cat # GTX22378, 1:100). Staining intensity or the percentage of positive cells was analyzed using ImageJ (National Institutes of Health, Bethesda, MD). |
Baseline and Week 24
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Histology - pSTAT3 and pSTAT6
Time Frame: Baseline and Week 24
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Histology Description: To determine the effects of dupilumab on Th2 pathway molecules (IL-4 and IL-13) and selected indicators and mediators of fibrosis in keloid tissue. Tissue was collected by skin biopsy during the baseline visit (pre-intervention) and Week 24 (post-intervention). Average of the markers at Baseline and Week 24 were analyzed to determine effect. Immunohistochemical staining was performed for the following markers: pSTAT3 (Cell Signaling Technology, CST4113, 1:50), and pSTAT6 (Abcam, ab236947, 1:2500). Staining intensity or the percentage of positive cells was analyzed using ImageJ (National Institutes of Health, Bethesda, MD). |
Baseline and Week 24
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Martina Porter, MD, Beth Israel Deaconess Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2021P000648
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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