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Clinical Trial to Evaluate Efficacy and Safety of Dupilumab in Localized Scleroderma (DupiMorph)

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ClinicalTrials.gov Identifier: NCT04200755
Recruitment Status : Not yet recruiting
First Posted : December 16, 2019
Last Update Posted : December 16, 2019
Sponsor:
Information provided by (Responsible Party):
Sabine Eming, University of Cologne

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.

Condition or disease Intervention/treatment Phase
Localized Scleroderma Drug: Dupilumab 300Mg Solution for Injection Other: Placebo Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, multi-center, double-blind, placebo controlled, parallel group, multiple dose, phase IIa trial
Masking: Double (Participant, Investigator)
Masking Description: Permuted blocks of varying length with allocation ratio (verum:placebo = 2:1); double-blind, i.e. patients and investigators are masked
Primary Purpose: Treatment
Official Title: A Randomized, Placebo-controlled Phase IIa Clinical Trial to Evaluate the Efficacy and Safety of Subcutaneous Dupilumab in Localized Scleroderma
Estimated Study Start Date : January 2020
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022


Arm Intervention/treatment
Experimental: Dupilumab
30 patients; Dupilumab s.c. injection; 2 ready-to-use syringes (600 mg) initial (V1), 1 ready-to-use syringe (300 mg) every 14 days (V2- V13) Dupilumab s.c. injection in healthy skin, 24 weeks
Drug: Dupilumab 300Mg Solution for Injection
First dose: 600 mg (2 syringes); subsequent doses: 300 mg (1 syringe)
Other Name: Dupixent

Placebo Comparator: Placebo
15 patients; placebo s.c. injection; 2 ready-to-use syringes initial (V1), 1 ready-to-use syringe every 14 days (V2-V13) placebo s.c. injection in healthy skin, 24 weeks
Other: Placebo
First dose: 2 syringes, no active substance; subsequent doses: 1 syringe, no active substance




Primary Outcome Measures :
  1. LoSCAT target lesion [ Time Frame: Baseline to End of Treatment Visit, 24 weeks ]
    Treatment response is assessed using the LoSCAT (Localized Scleroderma Cutaneous Assessment Tool). Target lesion will be assessed at Baseline and End of Treatment. Score reduction by 50% after 24 weeks (End of Treatment Visit V14) compared to Baseline Visit (V1) is defined as treatment response.


Secondary Outcome Measures :
  1. mLoSSI all lesions [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Change in mLoSSI (Localized Scleroderma Skin Activity Index) of all existing lesions during treatment, at End of Treatment Visit and during follow-up

  2. LoSDI all lesions [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Change in LoSDI (Localized Scleroderma Skin Damage Index) of all existing lesions during treatment, at End of Treatment Visit and during follow-up

  3. Number of lesions [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Count of all existing non-target and new lesions on the entire integument during treatment, at End of Treatment Visit and during follow-up

  4. DLQI [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Change in DermatoLogy Quality of life Index (DLQI). The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.

  5. RNAseq [ Time Frame: Baseline to End of Treatment Visit, 24 weeks ]
    Gene signature of localized scleroderma after Dupilumab treatment: RNA- seq of tissue biopsies obtained from the lesion (lilac ring, optional: center) before (baseline visit V1) and after treatment (EoT V14) and healthy skin before treatment

  6. RT-qPCR [ Time Frame: Baseline to End of Treatment Visit, 24 weeks ]
    Quantification of change in gene expression of genes identified by RNAseq in tissue of localized scleroderma patients after Dupilumab treatment: RT-qPCR of tissue biopsies obtained from the lesion (lilac ring, optional: center) before (baseline visit V1) and after treatment (End of Treatment Visit V14) and healthy skin before treatment

  7. Adverse events (AEs) [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Adverse events will be documented throughout the study

  8. Physical examination [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Physical examination (general appearance including skin, head and throat (head, eyes, ears, nose, and throat), lymph nodes, respiratory, cardiovascular, musculoskeletal, and neurological systems) will be documented throughout the study.

  9. Body weight [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Body weight will be documented throughout the study.

  10. Blood pressure [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Blood pressure will be documented throughout the study.

  11. Pulse rate [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Pulse rate will be documented throughout the study.

  12. Body temperature [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Body temperature will be documented throughout the study.

  13. Haemoglobin (Hgb) [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Haemoglobin (Hgb) will be documented at End of Treatment Visit and during follow-up

  14. Haematocrit (HcT) [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Haematocrit (HcT) will be documented at End of Treatment Visit and during follow-up

  15. Blood cell count [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Platelet count and differential White blood cell count will be documented at End of Treatment Visit and during follow-up

  16. Blood Enzymes [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Clinical Chemistry parameters (Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gamma-glutamyl transferase (GGT), alkaline phosphatase (AP), Lactic dehydrogenase (LDH), Creatine phosphokinase (CPK), Lipase) will be documented at End of Treatment Visit and during follow-up

  17. Clinical Chemistry [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Clinical Chemistry parameters (sodium, potassium, magnesium, chloride, calcium, phosphorus, blood glucose, Uric Acid, Albumin, Total protein, Bilirubin (total),Creatinine, blood urea nitrogen (BUN)) will be documented at End of Treatment Visit and during follow-up

  18. Anti-nuclear antibodies (ANAs) levels [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Change in anti-nuclear antibodies (ANAs) levels

  19. Serum cytokine levels [ Time Frame: Baseline to Follow-Up Visit, 48 weeks ]
    Change in serum levels of IL-4, IL-5, IL-13, periostin, dipeptidyl peptidase-4



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • Evidence or history of alcohol, medication or drug dependency
  • Evidence or history of neurotic personality, psychiatric illness, epilepsy or suicide risk
  • Diagnosis of other significant chronic inflammatory or autoimmune disorders.
  • 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.
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04200755


Contacts
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Contact: Sabine Schmied, Dr. 0049 221 478 ext 88153 sabine.schmied@uk-koeln.de

Locations
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Germany
Uniklinik Köln, Klinik für Dermatologie und Venerologie
Köln, Germany, 50924
Contact: Sabine Eming, Prof. Dr.    0049 221 478 ext 3196    sabine.eming@uni-koeln.de   
Contact: Nicolas Hunzelmann, Prof. Dr.    0049 221 478 ext 4517    nico.hunzelmann@uni-koeln.de   
Principal Investigator: Sabine Eming, Prof. Dr.         
Principal Investigator: Nicolas Hunzelmann, Prof. Dr.         
Sub-Investigator: Pia Moinzadeh, PD Dr.         
Helios St. Elisabeth Klinik Oberhausen, Klinik für Dermatologie, Venerologie und Allergologie
Oberhausen, Germany, 46045
Contact: Alexander Kreuter, Prof. Dr.    0049 208 8508 ext 8002    alexander.kreuter@helios-gesundheit.de   
Contact: Christian Tigges, Dr.    0049 208 8508 ext 8016    christian.tigges@helios-gesundheit.de   
Principal Investigator: Alexander Kreuter, Prof. Dr.         
Principal Investigator: Christian Tigges, Dr.         
Universitäts-Hautklinik Tübingen
Tübingen, Germany, 72076
Contact: Matthias Hahn, Dr.    0049 7071 29    matthias.hahn@med.uni-tuebingen.de   
Contact: Thomas Eigentler, Prof. Dr.    0049 7071 29 ext 85748    thomas.eigentler@med.uni-tuebingen.de   
Principal Investigator: Matthias Hahn, Dr.         
Principal Investigator: Thomas Eigentler, Prof. Dr.         
Sub-Investigator: Martin Röcken, Prof. Dr.         
Sponsors and Collaborators
University of Cologne
Investigators
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Principal Investigator: Sabine Eming, Prof. Dr. University of Cologne

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Responsible Party: Sabine Eming, Principal Coordinating Investigator, University of Cologne
ClinicalTrials.gov Identifier: NCT04200755    
Other Study ID Numbers: Uni-Koeln-3815
2019-002036-90 ( EudraCT Number )
First Posted: December 16, 2019    Key Record Dates
Last Update Posted: December 16, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sabine Eming, University of Cologne:
Morphea
Additional relevant MeSH terms:
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Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Connective Tissue Diseases
Skin Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs