Localized scleroderma MedDRA version: 21.1 Level: LLT Classification code 10009206 Term: Circumscribed scleroderma System Organ Class: 100000004859 MedDRA version: 21.0 Level: LLT Classification code 10018124 Term: Generalized scleroderma System Organ Class: 100000004859 MedDRA version: 20.0 Level: LLT Classification code 10027979 Term: Morphea System Organ Class: 100000004859
Conditions
Interventions
Product Name: Dupilumab
Product Code: Dupilumab
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Dupilumab
CAS Number: 1190264-60-8
Other descriptive name: SAR231
Sponsors
University of Cologne
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject is a male or female =18 years of age on the day the study informed consent is signed 2. Out-patient status 3. Caucasian, whereby the term comprises people with a light skin type that does not interfere with the evaluation (Fitzpatrick type I-V) 4. Morphea (plaque type) or Generalized localized scleroderma (affecting at least three anatomic sites) 5. At least one lesions with lilac ring (active phase of the disease); 6. Activity of LS within the last 12 month (as defined by progression of size or new developing plaque) 7. For women of childbearing potential: negative pregnancy test at Visit 1 8. For women of childbearing potetnial: Use of effective method of contraceptionfrom 4 weeks prior to enrolment, throughout the study treatment until 12 weeks after the last IMP dose 9. Written informed consent signed Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 42 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: 1. Systemic immunosuppressive therapy or UV therapy in doses relevant for the treatment of Morphea (plaque type) less than 3 months before enrolment. 2. Participation in another trial of IMPs or devices parallel to, or less than 6 months before or previous participation in this trial 3. Pregnancy or breastfeeding mother 4. Diagnosis of other significant chronic inflammatory or autoimmune disorders. 5. Topical immunosuppressive therapy less than 1 month before enrollment 6. Concurrent phototherapy 7. Known infection with helminths (helminthose) 8. 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. 9. Known hypersensitivity to any components of the IMP 10. Treatment with a live (attenuated) vaccine within 3 months prior to enrollment 11. Histroy of malignancy (except patients with complteels reated in situ carcinoma of the cervix, completely treated and resolved non-metastatic suamous or basal cell carcinoma or the skin). 12. Known diagnosis of active tuberculosis or non-tuberculous mycobacterial infections or latens untreated tuberculosis unless it is well documented by a specialist that the patient has been adequately treated. 13. Known diagnosis of HIV, HBV or HCV infection 14. Reguklar use (more than 2 visits per week) or a tanning booth/parlor 15. Known diagnosis of asthma including allergic asthma, with pathological lung function test and requirement of daily pharmaceutical treatment at the time of inclusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate, in comparison with placebo, the efficacy of Dupilumab in patients with Morphea (plaque type) or Generalized localized scleroderma (affecting at least three anatomic sites).;Secondary Objective: •To evaluate, in comparison with placebo, the effect of Dupilumab on: oDisease activity/skin damage score (mLoSSI/LoSDI) during treatment phase oDisease activity/skin damage score (mLoSSI/LoSDI) after end of treatment until 24 weeks after end of treatment oDisease activity/skin damage score (mLoSSI/LoSDI) of other existing (non-target) lesions and new lesions oThe potential for an attenuated gene signature of localized scleroderma (RNA-seq, RT-qPCR) oThe potential for an attenuated histology (quantity and quality of cellular composition, extracellular matrix composition, altered skin architecture) oOn the quality of life of patients (DLQI questionnaire) •To evaluate the safety profile of Dupilumab (AEs, physical examination, vital signs, clinical laboratory evaluations including hematology, biochemistry and urine analysis) •To evaluate immunogenicity of Dupilumab treatment ;Primary end point(s): To determine the efficacy of Dupilumab treatment response of patients with LS will be assessed by multiple measures which have been developed and validated in previous clinical trials and which are used within the ENLS (European Network for Localized Scleroderma) for the assessment of patients with LS (7). Personnel involved in data acquisition during the trial will be specifically trained in the assessment procedures. At baseline visit (V1) a single existing lesion with the highest mLoSSI activity index will be defined as target lesion. Treatment response is determined by change in mLoSSI (size of lesion, erythema, skin thickening) or LoSDI (dermal athrophy, subcutaneous atrophy, dyspigmentation) of the target lesion; score reduction by 50% after 24 weeks (EoT V14) compared to baseline (V1) is defined as treatment response. ;Timepoint(s) of evaluation of | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • mLoSSI of target lesion during treatment and during follow-up • LoSDI (dermal athrophy, subcutaneous atrophy, dyspigmentation) of target lesion during treatment, at EoT and during follow-up • Count of all existing non-target and new lesions on the entire integument during treatment, at EoT and during follow-up • mLoSSI and LoSDI of all existing non-target lesions and new lesions on the entire integument during treatment, at EoT and during follow-up • Gene signature of localized scleroderma after Dupilumab treatment: RNA-seq, RT-qPCR of tissue biopsies obtained from the lesion (lilac ring, optional: center) and healthy skin before (baseline visit V1) and after treatment (EoT V14) • Histology of localized scleroderma after Dupilumab treatment: tissue biopsies obtained from the lesion (lilac ring, optional: center) and healthy skin before (baseline visit/V1) and after treatment (EoT V14). Analysis of quantity and quality of cellular composition, extracellular matrix composition, altered skin architecture) • DermatoLogy Quality of life Index (DLQI) • Safety profile of Dupilumab: - Adverse events (AEs)/treatment-emergent adverse events (TEAEs) - Physical examination and body weight - Vital signs - Clinical laboratory evaluations including hematology, biochemistry • Anti-drug antibody levels (optional) • Anti-nuclear antibodies (ANAs) levels • Serum cytokine levels ;Timepoint(s) of evaluation of this end point: EoT V14 and/or FU visits V15 and V16 | — |
Countries
Germany
Contacts
Public ContactProject Manager
CTC Cologne
Outcome results
None listed