Safety Study of Bone Marrow Derived Stem Cells on Patients With Cutaneous Photoaging

Study Overview
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Brief Summary
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The purpose of this study is to determine whether a one-time injection of allogeneic mesenchymal bone marrow cells is safe and beneficial in the treatment of photodamage on the face.

Detailed Description
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Mesenchymal stem cells (MSCs) have been isolated from a number of sources, including bone marrow, adipose tissue, and peripheral blood. The MSCs manufactured for this study are a subset of non-hematopoietic stem cells derived from the bone marrow of healthy, adult donors. These cells have the ability to migrate to areas of injury in the body and can differentiate into multiple cell types, including cutaneous cells. In addition to contributing directly to repair of the skin by replacing damaged cells, MSCs also stimulate the body's own cells to regenerate. Though an increasing number of patients are seeking remedies for photoaged skin, current treatments, ranging from topical medications to laser peels, are not ideal methods for addressing the medical need. Because MSCs have been shown in clinical and non-clinical applications to be useful in wound healing, it is also possible that the cells will have a similar effect in skin rejuvenation. In the present study, we will determine the efficacy and safety of intravenously delivered MSCs in otherwise healthy patients with significant cutaneous photodamage.

Official Title
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A Phase I/II, Open-Label Study to Assess the Safety, Tolerability, and Preliminary Efficacy of a Single Intravenous Dose of Allogeneic Mesenchymal Bone Marrow Cells to Subjects for Cutaneous Photoaging

Conditions
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Chronic Effect of Ultraviolet Radiation on Photoaged Skin, Dermatologic Disorders

Intervention / Treatment
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* Biological: Allogeneic Mesenchymal Bone Marrow Cells


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Males and Females 40-70 years of age Good general health Fitzpatrick skin type I-III Fitzpatrick Wrinkle Scale class III. Fine to deep wrinkles, numerous lines with or without redundant skin folds Ability to understand and provide signed informed consent Reasonable expectation that subject will attend all scheduled safety follow-up visits Reasonable expectation that subject will maintain skin care regimen for the duration of the trial Adequate organ function Key Exclusion Criteria: History of malignant neoplasm within the past 5 years, or Stage 3 or 4 of any cancer at any time History of melanoma, leukemia, or lymphoma (any stage) Persistent pre-cancerous lesions (e.g., actinic keratosis) Active cutaneous infection of the head and/or neck Active cutaneous neoplasm in the treatment area Topical use of any anti-aging creams on the head and/or neck; if used, subject must agree to discontinue for the one year of follow-up on study Cosmetic or surgical treatment on face/neck in 6 months before study (includes laser, chemical peels, fillers, botulinum toxin) Prior treatment with stem cells Positive for hepatitis B, C or HIV Abnormal and clinically significant findings on screening ECG Abnormal and clinically significant findings on screening CT scan of the chest (without contrast) Clinically significant medical condition for which participation in the study would pose a safety risk to the subject Major surgery within 4 weeks of Study Day 1 Participation in another study with an investigational drug or device within 3 months prior to stem cell administration Participation in another study concurrent with the one-year duration of the trial History within the past year of drug or alcohol abuse Females known to be pregnant, lactating or having a positive pregnancy test (will be tested during screening) or planning to become pregnant during the study Sexually active males and females of child-bearing potential must use an effective method of birth control for duration of the study (approximately 13 months from the screening visit) Allergies to bovine and porcine products

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Allogeneic Mesenchymal Bone Marrow Cells<br>1550 nm Fraxel laser treatment (6-8 mJ, Level 2) to full face followed by IV infusion of Allogeneic Mesenchymal Bone Marrow Cells (0.5, 1.0, or 1.5 million cells/kg, up to 150 million cells) | Biological: Allogeneic Mesenchymal Bone Marrow Cells<br>* Subjects in Part 1, Cohorts 1-3 will receive a 1550 nm Fraxel laser (6-8 mJ, Level 2) treatment on the face followed by a single intravenous infusion of 0.5, 1.0, or 1.5 million mesenchymal cells per kg of body weight, not to exceed 150 million cells. Subjects in Part 2 will receive a 1550 Fraxel laser (6-8 mJ, Level 2) treatment on the face followed by a single intravenous infusion of mesenchymal cells at the Maximum Tolerated Dose, as determined by the safety results of Part 1. The dose in Part 2 is 1.5 million cells per kg, not to exceed a total of 150 million cells.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MSC Safety and Tolerability | The primary endpoint will be the safety and tolerability of IV administration of allogeneic mesenchymal bone marrow cells (aMBMC) during the twelve month study period as determined by the incidence and severity of adverse events, clinically significant changes on clinical laboratory tests, vital signs, physical and cutaneous examinations, 12 lead ECGs and CT scans of the chest (without contrast) | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MSC Efficacy | VISIA-CR 2D photography PRIMOS 3D images of face and neck VECTRA 3D photography Punch biopsy from the lateral canthal area to examine changes in decorin, fibrillin, elastin, MMPI, and procollagen-1 Subject self-assessment Independent evaluator assessment Principal investigator assessment Changes in RNA sequencing (from blood specimens) Changes in MMP-1, Ang-2, VEGF and FGF (from blood specimens) | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal Stem Cells, Bone Marrow Cells, Allogeneic Transplantation, Skin Wrinkling, Solar Aging of Skin, Intravenous Administration