Clinical trial NCT04200755: Clinical Trial to Evaluate Efficacy and Safety of Dupilumab in Localized Scleroderma
Official title: A Randomized, Placebo-controlled Phase IIa Clinical Trial to Evaluate the Efficacy and Safety of Subcutaneous Dupilumab in Localized Scleroderma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Localized Scleroderma
Keywords: Morphea
Lead sponsor: University of Cologne
Sponsor class: OTHER
First posted: 2019-12-16
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, multi-center, double-blind, placebo controlled, parallel group, multiple dose, phase IIa trial
Primary purpose: TREATMENT

Brief summary: The DupiMorph study evaluates the efficacy of Dupilumab in localized scleroderma patients. Dupilumab is approved in the US and EU for the treatment of moderate/severe atopic dermatitis and since 2018 in the US for severe asthma therapy.

Detailed description: Localized scleroderma (LS) comprises a heterogenous group of sclerotic skin disorders. The incidence of LS is reported to be approximately 27 cases/ 1x106 and is hence approximately 2-3-fold higher compared to systemic scleroderma. Although in most cases not lethal the disease can significantly impact quality of life. Depending on the location of fibrosis, the disorder can cause bone deformities, alopecia, skin atrophy or lesions with severe hypo-/hyperpigmentation.

The disease is pathomechanistically poorly understood and no effective therapy is currently approved. The most promising treatments up to date include methotrexate ± pulsed corticosteroids or phototherapy with PUVA or UVA1. Yet, the number of treated patients in these studies is low. The response rates are low and inconsistent with approximately 50% of patients treated with UVA1 experience a recurrence within three years. There are no studies on efficacy of topical corticosteroids in LS. Small pilot studies and few case reports describe regression of lesions after topical calcineurin inhibitors. In addition, current therapies can only be applied for a short time during the acute phase due to the side effect profile after long-term use (e.g. skin atrophy in response to topical steroids, skin cancer in response to long term UV therapy, multiple side effects by long- term use of methotrexate and/or corticosteroids). Hence, this study evaluates, in comparison with placebo, the efficacy of Dupilumab administered subcutaneously every 14 days in patients with Morphea (plaque type) or generalized localized scleroderma (affecting at least three anatomic sites).

Eligibility criteria: Inclusion Criteria:

* Subject is a male or female ≥18 years of age on the day the study informed consent is signed
* Out-patient status
* Caucasian
* Morphea (plaque type) or Generalized localized scleroderma (affecting at least three anatomic sites)
* At least one lesions with lilac ring (active phase of the disease);
* Activity of LS within the last 12 month (as defined by progression of size or new developing plaque)
* For women of childbearing potential: negative pregnancy test at Visit 1
* For women of childbearing potential: Use of effective method of contraception from 4 weeks prior to enrolment, throughout study treatment until 12 weeks after the last IMP dose.
* Written informed consent signed

Exclusion Criteria:

* Systemic immunosuppressive therapy or UV therapy less than 3 months before enrollment.
* Participation in another trial of IMPs or devices parallel to, or less than 6 months before or previous participation in this trial
* Pregnancy or breastfeeding mother
* Diagnosis of other significant chronic inflammatory or autoimmune disorders. Patients with the following autoimmune disorders are excluded from the study: Multiple sclerosis, primary biliary cirrhosis, type I diabetes mellitus. Patients with the following autoimmune disorders are regarded as eligible: Lichen sclerosus, vitiligo, alopecia arthritis, thyroid diseases (e.g. Hashimoto disease). Patients with any autoimmune disorder not listed above should only be included after consultation with the principal coordinating investigator.
* Topical immunosuppressive therapy less than 1 month before enrollment
* Concurrent phototherapy
* Known infection with helminths (helminthosis)
* Any condition or laboratory abnormality that, in the judgment of the investigator, would put the subject at unacceptable risk for participation in the study or may interfere with the assessments included in the study. E.g. uncontrolled psychiatric illness or history of clinical relevant drug abuse.
* Known hypersensitivity to any components of the IMP
* Treatment with a live (attenuated) vaccine within 3 months prior to enrollment
* History of malignancy (except patients with completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin)
* Known diagnosis of active tuberculosis or non-tuberculous mycobacterial infection or latent untreated tuberculosis unless it is well documented by a specialist that the patient has been adequately treated
* Known diagnosis of HIV, HBV or HCV infection
* Regular use (more than 2 visits per week) of a tanning booth/parlor
* Known diagnosis of asthma

Primary outcomes:
measure: LoSCAT target lesion
timeFrame: Baseline to End of Treatment Visit, 24 weeks
Secondary outcomes:
measure: mLoSSI all lesions
timeFrame: Baseline to Follow-Up Visit, 48 weeks
measure: LoSDI all lesions
timeFrame: Baseline to Follow-Up Visit, 48 weeks
measure: Number of lesions
timeFrame: Baseline to Follow-Up Visit, 48 weeks
measure: DLQI
timeFrame: Baseline to Follow-Up Visit, 48 weeks
measure: RNAseq
timeFrame: Baseline to End of Treatment Visit, 24 weeks
measure: RT-qPCR
timeFrame: Baseline to End of Treatment Visit, 24 weeks
measure: Adverse events (AEs)
timeFrame: Baseline to Follow-Up Visit, 48 weeks
measure: Physical examination
timeFrame: Baseline to Follow-Up Visit, 48 weeks
measure: Body weight
timeFrame: Baseline to Follow-Up Visit, 48 weeks
measure: Blood pressure
timeFrame: Baseline to Follow-Up Visit, 48 weeks
measure: Pulse rate
timeFrame: Baseline to Follow-Up Visit, 48 weeks
measure: Body temperature
timeFrame: Baseline to Follow-Up Visit, 48 weeks
measure: Haematocrit (HcT)
timeFrame: Baseline to Follow-Up Visit, 48 weeks
measure: Haemoglobin
timeFrame: Baseline to Follow-Up Visit, 48 weeks
measure: Blood cell count
timeFrame: Baseline to Follow-Up Visit, 48 weeks
measure: Blood Enzymes
timeFrame: Baseline to Follow-Up Visit, 48 weeks
measure: Clinical Chemistry
timeFrame: Baseline to Follow-Up Visit, 48 weeks
measure: Anti-nuclear antibodies (ANAs) levels
timeFrame: Baseline to Follow-Up Visit, 48 weeks
measure: Serum cytokine levels
timeFrame: Baseline to Follow-Up Visit, 48 weeks
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin Klinik für Dermatologie, Venerologie und Allergologie
city: Köln
country: Germany
facility: Uniklinik Köln, Klinik für Dermatologie und Venerologie
city: Oberhausen
country: Germany
facility: Helios St. Elisabeth Klinik Oberhausen, Klinik für Dermatologie, Venerologie und Allergologie
city: Tübingen
country: Germany
facility: Universitäts-Hautklinik Tübingen
Study officials:
affiliation: University of Cologne
name: Sabine Eming, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: