Keloid
Conditions
Keywords
keloid, keloid scar, hypertrophic scar, scar
Brief summary
The study investigates the efficacy and safety of dupilumab in the treatment of keloids
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.
Interventions
DRUGDupilumab
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.
Sponsors
Beth Israel Deaconess Medical Center
Regeneron Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Score of Patient and Observer Scar Assessment Scale (POSAS) From Baseline to Week 24 | 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: * The Patient Scar Assessment Scale (pain, pruritus, color, stiffness, thickness, bumpiness): The patient scores from 1 (normal) to 10 (worst) * The Observer Scar Assessment Scale (vascularity, pigmentation, thickness, relief, pliability, surface area): The clinician scores each item from 1 (normal skin) to 10 (worst scar imaginable). 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vancouver Scar Scale (VSS). | 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). * Vascularity: assessed by looking at the scar at resting and by blanching the scar and observing the rate and amount of blood return 1. Score 0: normal color and capillary refill 2. Score 1: pink scar with a slight increase in the local blood supply 3. Score 2: red scar with a significant increase in the local blood supply 4. Score 3: purple scar with excess local blood supply, scars which are congested and refill slowly or cannot be completely blanched * Pigmentation: The skin will be blanched with a piece of plastic to eliminate the effect of vascularity on skin color and compared with normal skin (Score: 0-3) |
| Dermatology Life Quality Index (DLQI). | Baseline and Week 24 | 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 |
| Histology | Baseline and Week 24 | 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). |
| Mean Change in Volume of Keloid to Show Improvement | Baseline and Week 24 | 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. |
| Histology - Tryptase | Baseline and Week 24 | 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). |
| Histology - pSTAT3 and pSTAT6 | Baseline and Week 24 | 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). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMartina Porter, MD
Beth Israel Deaconess Medical Center
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 27.3 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Sex/Gender, Customized Female | 13 Participants |
| Sex/Gender, Customized Male | 6 Participants |
| Sex/Gender, Customized Other | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
None listed