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

Localized Scleroderma Clinical Trial

— DupiMorph  

Official title:

A Randomized, Placebo-controlled Phase IIa Clinical Trial to Evaluate the Efficacy and Safety of Subcutaneous Dupilumab in Localized Scleroderma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04200755
• Other study ID #: Uni-Koeln-3815
• Secondary ID: 2019-002036-90
• Status: Recruiting
• Phase: Phase 2
• Start date: May 19, 2020
• Est. completion date: June 2025

Study information

• Verified date: November 2022
• Source: University of Cologne
• Contact: Sabine Schleicher, Dr.
• Phone: 0049 221 478
• Email: sabine.schleicher1[@]uk-koeln.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: June 2025
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Localized Scleroderma
• Scleroderma, Diffuse
• Scleroderma, Localized
• Scleroderma, Systemic

Intervention

Drug:
• Dupilumab 300Mg Solution for Injection
First dose: 600 mg (2 syringes); subsequent doses: 300 mg (1 syringe)

Other:
• Placebo
First dose: 2 syringes, no active substance; subsequent doses: 1 syringe, no active substance

Locations

Country	Name	City	State
Germany	Uniklinik Köln, Klinik für Dermatologie und Venerologie	Köln
Germany	Helios St. Elisabeth Klinik Oberhausen, Klinik für Dermatologie, Venerologie und Allergologie	Oberhausen
Germany	Universitäts-Hautklinik Tübingen	Tübingen

Sponsors (1)

Lead Sponsor	Collaborator
University of Cologne

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	LoSCAT target lesion	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.	Baseline to End of Treatment Visit, 24 weeks
Secondary	mLoSSI all lesions	Change in mLoSSI (Localized Scleroderma Skin Activity Index) of all existing lesions during treatment, at End of Treatment Visit and during follow-up	Baseline to Follow-Up Visit, 48 weeks
Secondary	LoSDI all lesions	Change in LoSDI (Localized Scleroderma Skin Damage Index) of all existing lesions during treatment, at End of Treatment Visit and during follow-up	Baseline to Follow-Up Visit, 48 weeks
Secondary	Number of lesions	Count of all existing non-target and new lesions on the entire integument during treatment, at End of Treatment Visit and during follow-up	Baseline to Follow-Up Visit, 48 weeks
Secondary	DLQI	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.	Baseline to Follow-Up Visit, 48 weeks
Secondary	RNAseq	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	Baseline to End of Treatment Visit, 24 weeks
Secondary	RT-qPCR	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	Baseline to End of Treatment Visit, 24 weeks
Secondary	Adverse events (AEs)	Adverse events will be documented throughout the study	Baseline to Follow-Up Visit, 48 weeks
Secondary	Physical examination	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.	Baseline to Follow-Up Visit, 48 weeks
Secondary	Body weight	Body weight will be documented throughout the study.	Baseline to Follow-Up Visit, 48 weeks
Secondary	Blood pressure	Blood pressure will be documented throughout the study.	Baseline to Follow-Up Visit, 48 weeks
Secondary	Pulse rate	Pulse rate will be documented throughout the study.	Baseline to Follow-Up Visit, 48 weeks
Secondary	Body temperature	Body temperature will be documented throughout the study.	Baseline to Follow-Up Visit, 48 weeks
Secondary	Haematocrit (HcT)	Haematocrit (HcT) will be documented at End of Treatment Visit and during follow-up	Baseline to Follow-Up Visit, 48 weeks
Secondary	Haemoglobin	Haemoglobin (Hgb) will be documented at End of Treatment Visit and during follow-up	Baseline to Follow-Up Visit, 48 weeks
Secondary	Blood cell count	Platelet count and differential White blood cell count will be documented at End of Treatment Visit and during follow-up	Baseline to Follow-Up Visit, 48 weeks
Secondary	Blood Enzymes	Clinical Chemistry parameters (Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gamma-glutamyl transferase (GGT), Lactic dehydrogenase (LDH)) will be documented at End of Treatment Visit and during follow-up	Baseline to Follow-Up Visit, 48 weeks
Secondary	Clinical Chemistry	Clinical Chemistry parameters (Creatinine) will be documented at End of Treatment Visit and during follow-up	Baseline to Follow-Up Visit, 48 weeks
Secondary	Anti-nuclear antibodies (ANAs) levels	Change in anti-nuclear antibodies (ANAs) levels	Baseline to Follow-Up Visit, 48 weeks
Secondary	Serum cytokine levels	Change in serum levels of IL-4, IL-5, IL-13, periostin, dipeptidyl peptidase-4	Baseline to Follow-Up Visit, 48 weeks