E-CEL UVEC Cells as an Adjunct Cell Therapy for the Arthroscopic Rotator Cuff Repair in Adults
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04057833|
Recruitment Status : Recruiting
First Posted : August 15, 2019
Last Update Posted : November 21, 2019
This is a phase 1b investigator-initiated clinical trial that will evaluate the safety and feasibility of E-CEL UVEC® cells with the aim of improving outcomes for patients with full-thickness rotator cuff tears who undergo arthroscopic surgical repair. Animal models of rotator cuff repair performed by the investigator using murine E-CEL cells in a fibrin carrier vehicle demonstrated increased supraspinatus tendon strength and collagen organization with no observable deleterious side effects compared to surgical repair with the carrier vehicle alone.
After thawing and washing, allogeneic E-CEL UVEC cells will be resuspended in two different solutions; one to deliver the cells under arthroscopic guidance into the supraspinatus tendon repair site and the other to deliver cells into the muscle adjacent to the tendon repair site. Cells delivered to the tendon repair site will be resuspended in human plasma (derived from a peripheral blood sample drawn from the patient), then combined with allogeneic, pharmaceutical grade human thrombin to generate a fibrin matrix, simultaneously with implantation of the cells into the tendon using a two syringes joined with a luer-lock connection under arthroscopic guidance . Cells delivered to the muscle adjacent to the tendon repair site will be resuspended in infusion solution [6.0% Dextran 40 and 10.0% human serum albumin (HSA)], then directly implanted into the muscle.
|Condition or disease||Intervention/treatment||Phase|
|Rotator Cuff Tears Muscle Atrophy or Weakness Tendon Rupture - Shoulder Safety Issues||Drug: E-CEL UVEC||Phase 1|
Full-thickness rotator cuff tears present a clinical challenge, often with occurrence of re-tears after surgical repair and a slow rate of complete functional recovery, which limits daily functional tasks and has negative impacts on qualify-of-life. The frequency of failed healing and re-tear following repair is more pronounced in patients over age 60 due to age-related, intrinsic degenerative changes involving the muscle, tendon, and enthesis.
Currently there is no approved adjunct biological therapy to standard-of- care arthroscopic surgical repair for acceleration of healing, reducing time-to complete functional recovery, and decreasing the rate of re-tear.
Healing of the enthesis, the site of tendon attachment to the bone, can be compromised due to microvascular and vascular niche deficiencies resulting from various causes including aging, prior injuries, and/or tissue degeneration. Administration of exogenous allogeneic engineered CD31+ endothelial cells (E-CEL UVEC® cells) at the surgical repair site of simulated supraspinatus tendon tear in animal models has been shown to positively affect the tissue vascular niche, where tissue regeneration and repair occur, resulting in accelerated healing and a significant improvement in tendon attachment strength at the enthesis repair site.
E-CEL UVEC cells are derived proprietary allogeneic human umbilical vein endothelial cells produced under cGMP and cGTP regulations. The cells are genetically modified by a transduction of Ad5 E4ORF1 gene. The gene has endothelial pro-survival properties. It is found naturally in adenoviruses that have near ubiquitous human exposure.
The non-clinical and CMC information of E-CEL UVEC cells has been reviewed and accepted by the US FDA as part of IND #018355, titled "AB-205-001". Specifically, E-CEL UVEC cells comprise the cellular component of AB-205, an experimental engineered cell therapy, that will be administered intravenously to subjects with relapsed lymphoma after treatment with high dose therapy and autologous stem cell transplant in a clinical trial sponsored by Angiocrine Bioscience, Inc. Pre-clinical information of E-CEL UVEC cells will be provided via cross-reference to Angiocrine's IND in support of this Investigator Initiated Trial.
There is currently no approved adjunct biologic therapy to improve surgical repairs of full rotator cuff tear, enhance post-operative recovery, and decrease the risk of re-tear. Therefore, it is reasonable to study, via an Investigator Initiated Trial, the safety and feasibility of local implantation of E-CEL UVEC cells along with standard-of-care arthroscopic surgical repair of full rotator cuff tears. The E-CEL UVEC cell dose will be much lower than what is needed for systemic application.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Open-Label, Single-Center Investigator Initiated Trial (IIT) of E-CEL UVEC Cells as an Adjunct Cell Therapy for the Arthroscopic Rotator Cuff Repair in Adults|
|Actual Study Start Date :||November 20, 2019|
|Estimated Primary Completion Date :||November 26, 2020|
|Estimated Study Completion Date :||November 26, 2020|
Experimental: E-CEL UVEC
Patients will receive an injection of the Cell therapy vehicle into their supraspinatus muscle and tendon at the time of rotator cuff repair.
E-CEL UVEC cells suspended in autologous plasma and combined with thrombin at the implantation site (tendon delivery).
E-CEL UVEC cells suspended in 6.0% Dextran 40 and 10.0% human serum albumin (HSA) (infusion solution) (muscle delivery).
Drug: E-CEL UVEC
Local implantation of E-CEL UVEC cells at the supraspinatus tendon repair site
- Short-term safety [ Time Frame: 0 surgery to +11 days post op ]The primary study outcomes are measures of local and systemic safety and toxicity via adverse event (AE) logs (post-operative day 0 to Day 11). AE are evaluated using a 5 point severity scale to grade the AE, 1 (mild) to 5 (death/ fatal).
- Long-term safety [ Time Frame: post-operative 90 day to 1 year following the surgical repair ]The primary study outcomes are measures of local and systemic safety and toxicity via symptom reporting (post-operative day +90 to 1 year post-op). Symptom reporting will evaluate pain and swelling based on a 0 to 100mm visual analog scale range, in addition to further symptom reporting.
- MRI [ Time Frame: post-operative 90 day to 1 year ]Re-tear rate based on clinical and MRI evaluation for MRI assessments of muscle and tendon quality, measured as a percentage of total volume (%).
- Strength [ Time Frame: post-operative 90 day to 1 year ]Shoulder strength during regular intervals post-operatively up to 1 year. BioDex system 3 will measure Peak Toque in Nm, scapular plane abduction strength 0-90 degrees.
- PROMS [ Time Frame: post-operative 90 day to 1 year ]Patient-reported outcomes post-operatively up to 1 year. ASES affected vs unaffected shoulder score (each test has a maximum score of 100 points).
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): NCT04057833
|Contact: Camila Carballo, PhD||(212) email@example.com|
|Contact: Daniel Edon, MS||(212) firstname.lastname@example.org|
|United States, New York|
|Hospital for Special Surgery||Recruiting|
|New York, New York, United States, 10021|
|Contact: Danie Edon, MS, CSCS 212-774-7833 email@example.com|
|Principal Investigator:||Scott Rodeo, MD||Hospital for Special Surgery, New York|