A Study of FCX-013 Plus Veledimex for the Treatment of Moderate to Severe Localized Scleroderma (Morphea)

Study Overview
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Brief Summary
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A two-component therapeutic consisting of FCX-013 and veledimex for the treatment of localized scleroderma (or morphea). The first component, FCX-013, is autologous human fibroblasts genetically-modified using lentivirus and encoded for matrix metalloproteinase 1 (MMP-1), a protein responsible for breaking down collagen. FCX-013 is designed to be injected under the skin at the location of the fibrotic lesions where the genetically-modified fibroblast cells will produce MMP-1 to break down excess collagen accumulation. With the FCX-013 therapy, the patient will take an oral compound (Veledimex) to induce MMP-1 protein expression from the injected cells. Once the fibrosis is resolved, the patient will stop taking the oral compound which will stop further MMP-1 production from the injected cells. FCX-013 plus veledimex is being developed in anticipation of improving skin function in patients by resolving fibrotic lesions and normalizing dermal collagen production

Detailed Description
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Castle Creek is developing a two-component therapeutic product for the treatment of moderate to severe localized scleroderma (morphea). The first component is FCX-013, an autologous genetically modified human dermal fibroblast (GM-HDFs) cell product that is genetically modified with a lentiviral vector (LV) to express human matrix metalloproteinase 1 (MMP1). MMP1 is also known as interstitial collagenase or fibroblast collagenase and is an enzyme that under normal physiological conditions breaks down the extracellular matrix. Specifically, MMP1 breaks down interstitial collagens, types I, II and III. In addition, the FCX-013 cells are also transduced with genetic constructs that encode the RheoSwitch Therapeutic System® (RTS®) an inducible promotor system that in the presence of a small molecule activator ligand controls expression of the MMP1 gene. The RTS® is activated to express MMP1 by the oral administration of the small molecule component. The purpose of this open-label single arm Phase 1/2 study is to investigate the safety and effectiveness of FCX-013 plus veledimex.

Official Title
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A Phase 1/2 Study of a Combination of FCX-013 (Genetically-Modified Autologous Human Dermal Fibroblasts) Plus Veledimex for the Treatment of Moderate to Severe Localized Scleroderma (Morphea)

Conditions
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Morphea, Scleroderma, Localized, Scleroderma

Intervention / Treatment
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* Genetic: FCX-013
* Drug: veledimex


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is an adult, ≥ 18 years of age with moderate to severe localized scleroderma/morphea with sclerotic lesions which have been unresponsive to standard of care therapy. Subject has stable control of localized disease (clinically inactive) over the 3 months prior to Screening and through Baseline Subject has not participated in previous clinical research study in the 3 months prior to Screening and through Baseline Subject has provided informed written consent Female subjects of childbearing potential and male subjects engaging in sexual activity that could lead to pregnancy agree to use adequate birth control regimen Subject is able to understand the study, cooperate with the study procedures and willing to return to the clinic for the required follow-up visits Exclusion Criteria: Subject has a clinically significant skin disorder other than localized scleroderma/morphea in the anatomical area of interest Subject has localized scleroderma/morphea only located on the face or over a joint, or lesions that can be successfully managed with topical medications or phototherapy Subject has symptoms consistent with systemic scleroderma that have not been stable, or that require treatment that has not been stable for 3 months prior to Screening and through Baseline Subject has been treated with UVA1 phototherapy within 2 months prior to Baseline Subject requires treatment with a non-stable regimen of systemic immunosuppressive therapy, for any medical condition, or plans to initiate such treatment during the study period Subject requires treatment with a non-stable regimen of physical therapy, for localized scleroderma/morphea, or plans to initiate such treatment during the study period. Subject has any medical instability limiting ability to travel to the investigative center. Subject has clinical signs of infection at (or in close proximity to) the target lesion. Subject has a history of, or current, malignancy at/near site of injection (except basal cell carcinoma or squamous cell carcinoma that have been treated) Subject has a history of, or current, clinically significant liver abnormalities. Subject has a history of, or current, clinically significant cardiac abnormalities, or a significant abnormality on ECG Subject has clinically significant laboratory abnormalities Subject has active infection with human immunodeficiency virus (HIV), or hepatitis B/C Subject has an active drug or alcohol addiction Subject has any known allergy to any of the constituents of the product Subject has received an interventional chemical or biological investigational study product for the specific treatment of localized scleroderma in the 3 months prior to Screening and through Baseline Subject is pregnant or nursing or plans to become pregnant or nurse during the study period

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FCX-013 + veledimex<br>Following the injection of FCX-013, subjects will initiate a 14-day course of veledimex to be taken orally daily | Genetic: FCX-013<br>* FCX-013 is a genetically modified cell product obtained from the subject's own skin cells (autologous fibroblasts). The cells are expanded and genetically modified to express metalloproteinase-1 (MMP-1) under the control of a RheoSwitch (RTS®) system. FCX-013 cell suspension is injected intradermally.<br>* Other names: Genetically-Modified Autologous Human Dermal Fibroblasts;Drug: veledimex<br>* Veledimex, is a small molecule which activates the RTS to induce expression of MMP-1 and is and provided as a liquid filled gelatin capsule for oral administration<br>* Other names: a small-molecule activator ligand for the RheoSwitch (RTS®) system;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the Safety of FCX-013 Plus Veledimex | Safety evaluations include assessment of treatment-emergent adverse events (TEAEs), including serious adverse events (SAEs); change in clinical laboratory values; change in vital signs; change in electrocardiograms (ECGs); and incidence of replication-competent lentivirus (RCL) antibodies. | Study initiation through study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the Antifibrotic Effects of FCX-013 Plus Veledimex | Evaluate the antifibrotic effects of FCX-013 plus veledimex | Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Morphea