E-CEL UVEC Cells as an Adjunct Cell Therapy for the Arthroscopic Rotator Cuff Repair in Adults

Sponsor

Hospital for Special Surgery, New York (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04057833

Collaborator

Angiocrine Bioscience (Industry)

Enrollment

Location

Arm

40.1

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Allogeneic E-CEL UVEC cells will be delivered to the tendon repair site and to the muscle adjacent to the tendon repair site.

Condition or Disease	Intervention/Treatment	Phase
Rotator Cuff Tears Muscle Atrophy or Weakness Tendon Rupture - Shoulder Safety Issues	Drug: E-CEL UVEC	Phase 1

Detailed Description

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.

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.

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. This trial will investigate 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. E-CEL UVEC cells are proprietary allogeneic human umbilical vein endothelial cells produced under cGMP and cGTP regulations.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 :

Nov 20, 2019

Anticipated Primary Completion Date :

Jan 26, 2023

Anticipated Study Completion Date :

Mar 26, 2023

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Short-term safety [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).

Secondary Outcome Measures

Long-term safety [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 [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 [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 [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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adults aged 45-70 years old
Diagnosis of full-thickness supraspinatus tendon tear by MRI and physical examination
Tendon retraction 1 to 3 cm on MRI
Goutallier score ≤ grade 2.
Failed standard non-operative treatments for tendon tear including a minimum of 3 months of physical therapy as well as oral anti-inflammatory medications, subacromial steroid injection, activity modification, etc.

Exclusion Criteria:

Tears of any cuff tendon other than the supraspinatus
Frank signs of glenohumeral osteoarthritis on MRI
Diagnosis of acute tendon tear
Lack of significant pain and/or loss of function due to tendon tear History of previous rotator cuff repair
History of upper extremity fracture or other moderate to severe upper extremity trauma
BMI < 20 or > 35
Diagnosis of Type I or type II diabetes, or other metabolic disorders
Previous history of cancer. Subjects with cervical carcinoma in situ or localized basal or squamous cell carcinoma treated with definitive surgery are eligible.
Diagnosis of an autoimmune disorder Know history of HIV
Current use of nicotine products
History of diabetes, malignancy within 5 years of the procedure, immunosuppression, autoimmune or connective tissue disorders such as lupus or rheumatoid arthritis, schizophrenia or other psychiatric disorder that could interfere with postoperative rehabilitation, or other disability that would obviously adversely impact the patient's ability to participate in standard postoperative rehabilitation
Pregnancy
Inability to comply with post-operative rehabilitation
Hypersensitivity reactions to bovine (cow) proteins