Clinical trial NCT04988022: Dupilumab in the Treatment of Keloids
Official title: Defining Reversal of Keloid Lesions by Th2 Targeting With Dupilumab Treatment
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Keloid
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
name: Sanofi
First posted: 2021-08-03
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study is a prospective, randomized, double blind, placebo-controlled clinical trial.

The study will include a total of 44 subjects with clinically measurable keloid lesions. At least 50% of subjects (at least 22 out of the 44 subjects) will also have documented diagnosis of concomitant type 2 atopic/allergic) inflammatory diseases. In Phase I, subjects will be randomized (3:1) to either receive weekly dupilumab or placebo for 24 weeks. At Week 24, both groups will enter Phase II of the study in which all subjects will receive weekly doses of dupilumab up to Week 52. The treatment period will conclude at Week 52.

Detailed description: This study is a prospective, randomized, double blind, placebo-controlled clinical trial.

The study will include a total of 44 subjects with clinically measurable keloid lesions. At least 50% of subjects (at least 22 out of the 44 subjects) will also have documented diagnosis of concomitant type 2 atopic/allergic) inflammatory diseases. In Phase I, subjects will be randomized (3:1) to either receive weekly dupilumab or placebo for 24 weeks. At Week 24, both groups will enter Phase II of the study in which all subjects will receive weekly doses of dupilumab up to Week 52. The treatment period will conclude at Week 52.

After providing consent, subjects will be assessed for study eligibility during the screening period (within 28 days of Baseline), which includes a review of the subject's past and current medical conditions as well as a family history of keloids, atopic dermatitis (AD), asthma and other atopic diseases, detailed review of past and current medications, review of past topical and systemic treatments/therapies and invasive treatments (including surgery, radiation, and cryotherapy) for keloids, limited physical examination, clinical assessments (number, location and measurements via tonometer and calipers). Measurements of keloid lesions will be standardized and performed using Verneir Calipers. These are accurate to the nearest 0.01mm in their measurement of all dimensions. Keloid distensibility (hardness) will be measured using a tonometer, a tool that has been adapted for use in systemic sclerosis and can give insight into softening of lesions.

Subjects who meet inclusion criteria for eligibility will undergo Baseline assessments at Week 0, including clinical assessments (number, location and measurements via tonometer and calipers), review of concomitant medications, standardized clinical photography, questionnaires (a Dermatology Life Quality Index (DLQI), and a Keloid-Quality of Life Index (K-QLI) questionnaire), and additional skin assessments if he/she concurrently has atopic dermatitis (EASI, IGA, BSA and SCORAD will be used to evaluate existing atopic dermatitis). Blood samples and skin biopsies will be collected for mechanistic studies (described below) at various timepoints for RNA, DNA and protein analyses, as well as for analyses of IgE and serum CRP. Two 4.5 mm biopsies will be performed at Baseline: one from a keloid lesion and one from an adjacent non-lesional area. Non-lesional biopsies will mimic nascent trauma (e.g. surgery, or other inflammatory processes) and evaluate the effectiveness of dupilumab in preventing new keloid lesion formation.

Subjects will return for visits at weeks 4, 8, 16, 24, 28, 36, 48, and 52 following study treatment initiation for repeat clinical assessments (number, location, and measurements via tonometer and calipers), medication reviews, blood and biopsy collection, surveys, and monitoring for adverse events. At week 24 a second lesional biopsy will be performed (from the same keloid area biopsy at baseline, but away from the previous biopsy scar), and at week 48 both a lesional (again from the same keloid, but away from prior biopsies) and a non-lesional biopsy will be performed. Bloods will be done at baseline, week 4, week 16, week 24, week 48. The biopsy sites as well as other lesional areas will be monitored at each subsequent visit by clinical assessment (number, location and measurements via tonometer and calipers) and standardized clinical photography.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects ≥ 18 years of age at the time of signing the informed consent document.
* Subject is able to understand and voluntarily sign an informed consent document prior to participation in any study assessments or procedures.
* Subject is able to adhere to the study visit schedule and other protocol requirements.
* Subject has at least two clinically measurable keloid lesions on the trunk and/or extremities, that failed prior minimally invasive treatments for keloids including topicals and intralesional steroid injections. However, at least one keloid should not have been treated with surgery, cryotherapy, radiation, or any other procedure that leads to a deformity that interferes with proper clinical assessments.
* At least 50% of the subjects: subject has documented diagnosis of concomitant type 2 (atopic/allergic) (e.g., active AD, asthma, chronic rhinosinusitis with nasal polyposis, food allergy confirmed by skin prick test or food allergen specific IgE, seasonal allergies, other confirmed allergies).
* Subject is judged to be in otherwise good overall health as judged by the investigator, based on medical history, physical examination, and laboratory testing. (NOTE: The definition of good health means a subject does not have uncontrolled significant co-morbid conditions).
* Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. While on investigational product and for at least 28 days after taking the last dose of investigational product, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options described below:

Option 1: Any one of the following highly effective contraceptive methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy.

OR

Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural \[animal\] membrane \[for example, polyurethane\]); PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.

The female subject's chosen form of contraception must be effective by the time the female subject is randomized into the study (for example, hormonal contraception should be initiated at least 28 days before randomization).

Exclusion Criteria:

* Subject has a persistent or recurring bacterial infection requiring systemic antibiotics, or clinically significant viral or fungal or helminth parasitic infections, within 2 weeks of the Screening Visit. Any treatment of such infections must have been completed at least 2 weeks prior to the Screening Visit and no new/recurrent infections should have occurred prior to the Baseline Visit.
* Subject with current or history of positive human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency (i.e. Common Variable Immunodeficiency \[CVID\]), hepatitis B or C, or active or untreated latent tuberculosis.
* Subject has clinically significant (as determined by the investigator) renal, hepatic, hematologic, intestinal, endocrine, pulmonary, cardiovascular, neurological, psychiatric, immunologic, or other major uncontrolled diseases that will affect the health of the subject during the study, or interfere with the interpretation of study results.
* Subject has a suspected or active lymphoproliferative disorder or malignancy; OR a history of malignancy within 5 years before the Baseline assessment, except for completely treated in situ non-melanoma skin and cervical cancers without evidence of metastasis.
* Subject was treated previously with dupilumab.
* Subject has received a live attenuated vaccine ≤ 30 days prior to study initiation.
* History of adverse systemic or allergic reactions to any component of the study drug.
* Severe, untreated asthma or a history of life-threatening asthma exacerbations while on appropriate regimen of anti-asthmatic medications.
* Use of systemic immunosuppressive medications, including, but not limited to, cyclosporine, systemic or intralesional corticosteroids, mycophenolate mofetil, azathioprine, methotrexate, tacrolimus, or ultraviolet (UV) phototherapy with or without Psoralen Ultraviolet A (PUVA) therapy within 4 weeks prior to trial initiation.
* Use of an oral JAK inhibitor (tofacitinib, ruxolitinib) within 12 weeks prior to the Baseline visit.
* Subject has used topical corticosteroids, and/or tacrolimus, and/or pimecrolimus on any keloid lesions within 1 week prior to the Baseline visit. These will be allowed during the study on areas of atopic dermatitis (if applicable) but not on any keloid lesions.
* Female subject who is pregnant or breast feeding
* Subject currently uses or plans to use anti-retroviral therapy at any time during the study.

Primary outcomes:
measure: Change from baseline in dimensions of keloid lesions at 24 weeks
timeFrame: baseline and 24 weeks
Secondary outcomes:
measure: Change from baseline in dimensions of keloid lesions at weeks 4, 16, 24, 48, and 52 of treatment with dupilumab
timeFrame: baseline and weeks 4, 16, 24, 48, and 52
Other outcomes:
measure: Dermatology Life Quality Index (DLQI)
timeFrame: Week 52
measure: Keloid-Quality of Life Index (K-QLI) questionnaire
timeFrame: Week 52
measure: Keloid distensibility
timeFrame: Week 52
measure: Eczema Area and Severity Index (EASI) score
timeFrame: Week 52
measure: Investigator Global Assessment (IGA) of disease score
timeFrame: Week 52
measure: Body Surface Area (BSA) affected with disease
timeFrame: Week 52
measure: SCORing Atopic Dermatitis (SCORAD)
timeFrame: Week 52
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Emma Guttman, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: