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

Primary Purpose

Rotator Cuff Tears, Muscle Atrophy or Weakness, Tendon Rupture - Shoulder

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
E-CEL UVEC
Sponsored by
Hospital for Special Surgery, New York
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rotator Cuff Tears focused on measuring Cell Therapy, Supraspinatus tendon, Systemic safety and toxicity, Muscle and Tendon quality

Eligibility Criteria

45 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Hospital for Special Surgery

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

E-CEL UVEC

Arm Description

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).

Outcomes

Primary Outcome Measures

Short-term safety
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
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
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
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
Patient-reported outcomes post-operatively up to 1 year. ASES affected vs unaffected shoulder score (each test has a maximum score of 100 points).

Full Information

First Posted
July 30, 2019
Last Updated
April 5, 2023
Sponsor
Hospital for Special Surgery, New York
Collaborators
Angiocrine Bioscience
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1. Study Identification

Unique Protocol Identification Number
NCT04057833
Brief Title
E-CEL UVEC Cells as an Adjunct Cell Therapy for the Arthroscopic Rotator Cuff Repair in Adults
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 20, 2019 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
October 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital for Special Surgery, New York
Collaborators
Angiocrine Bioscience

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rotator Cuff Tears, Muscle Atrophy or Weakness, Tendon Rupture - Shoulder, Safety Issues
Keywords
Cell Therapy, Supraspinatus tendon, Systemic safety and toxicity, Muscle and Tendon quality

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
E-CEL UVEC
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
E-CEL UVEC
Intervention Description
Local implantation of E-CEL UVEC cells at the supraspinatus tendon repair site
Primary Outcome Measure Information:
Title
Short-term safety
Description
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).
Time Frame
0 surgery to +11 days post op
Secondary Outcome Measure Information:
Title
Long-term safety
Description
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.
Time Frame
post-operative 90 day to 1 year following the surgical repair
Title
MRI
Description
Re-tear rate based on clinical and MRI evaluation for MRI assessments of muscle and tendon quality, measured as a percentage of total volume (%).
Time Frame
post-operative 90 day to 1 year
Title
Strength
Description
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.
Time Frame
post-operative 90 day to 1 year
Title
PROMS
Description
Patient-reported outcomes post-operatively up to 1 year. ASES affected vs unaffected shoulder score (each test has a maximum score of 100 points).
Time Frame
post-operative 90 day to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott Rodeo, MD
Organizational Affiliation
Hospital for Special Surgery, New York
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital for Special Surgery
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20436053
Citation
Voigt C, Bosse C, Vosshenrich R, Schulz AP, Lill H. Arthroscopic supraspinatus tendon repair with suture-bridging technique: functional outcome and magnetic resonance imaging. Am J Sports Med. 2010 May;38(5):983-91. doi: 10.1177/0363546509359063.
Results Reference
background
PubMed Identifier
6991502
Citation
Ippolito E, Natali PG, Postacchini F, Accinni L, De Martino C. Morphological, immunochemical, and biochemical study of rabbit achilles tendon at various ages. J Bone Joint Surg Am. 1980;62(4):583-98.
Results Reference
background
PubMed Identifier
26635616
Citation
Tempfer H, Traweger A. Tendon Vasculature in Health and Disease. Front Physiol. 2015 Nov 18;6:330. doi: 10.3389/fphys.2015.00330. eCollection 2015.
Results Reference
background
PubMed Identifier
26188783
Citation
Hein J, Reilly JM, Chae J, Maerz T, Anderson K. Retear Rates After Arthroscopic Single-Row, Double-Row, and Suture Bridge Rotator Cuff Repair at a Minimum of 1 Year of Imaging Follow-up: A Systematic Review. Arthroscopy. 2015 Nov;31(11):2274-81. doi: 10.1016/j.arthro.2015.06.004. Epub 2015 Jul 15.
Results Reference
background
PubMed Identifier
17574875
Citation
Rodeo SA. Biologic augmentation of rotator cuff tendon repair. J Shoulder Elbow Surg. 2007 Sep-Oct;16(5 Suppl):S191-7. doi: 10.1016/j.jse.2007.03.012. Epub 2007 Jun 15.
Results Reference
background
PubMed Identifier
22709690
Citation
Butler JM, Gars EJ, James DJ, Nolan DJ, Scandura JM, Rafii S. Development of a vascular niche platform for expansion of repopulating human cord blood stem and progenitor cells. Blood. 2012 Aug 9;120(6):1344-7. doi: 10.1182/blood-2011-12-398115. Epub 2012 Jun 18.
Results Reference
background
PubMed Identifier
21068842
Citation
Ding BS, Nolan DJ, Butler JM, James D, Babazadeh AO, Rosenwaks Z, Mittal V, Kobayashi H, Shido K, Lyden D, Sato TN, Rabbany SY, Rafii S. Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration. Nature. 2010 Nov 11;468(7321):310-5. doi: 10.1038/nature09493.
Results Reference
background
PubMed Identifier
22036563
Citation
Ding BS, Nolan DJ, Guo P, Babazadeh AO, Cao Z, Rosenwaks Z, Crystal RG, Simons M, Sato TN, Worgall S, Shido K, Rabbany SY, Rafii S. Endothelial-derived angiocrine signals induce and sustain regenerative lung alveolarization. Cell. 2011 Oct 28;147(3):539-53. doi: 10.1016/j.cell.2011.10.003.
Results Reference
background
PubMed Identifier
22968453
Citation
Candotti F, Shaw KL, Muul L, Carbonaro D, Sokolic R, Choi C, Schurman SH, Garabedian E, Kesserwan C, Jagadeesh GJ, Fu PY, Gschweng E, Cooper A, Tisdale JF, Weinberg KI, Crooks GM, Kapoor N, Shah A, Abdel-Azim H, Yu XJ, Smogorzewska M, Wayne AS, Rosenblatt HM, Davis CM, Hanson C, Rishi RG, Wang X, Gjertson D, Yang OO, Balamurugan A, Bauer G, Ireland JA, Engel BC, Podsakoff GM, Hershfield MS, Blaese RM, Parkman R, Kohn DB. Gene therapy for adenosine deaminase-deficient severe combined immune deficiency: clinical comparison of retroviral vectors and treatment plans. Blood. 2012 Nov 1;120(18):3635-46. doi: 10.1182/blood-2012-02-400937. Epub 2012 Sep 11.
Results Reference
background
PubMed Identifier
28297579
Citation
Gori JL, Butler JM, Kunar B, Poulos MG, Ginsberg M, Nolan DJ, Norgaard ZK, Adair JE, Rafii S, Kiem HP. Endothelial Cells Promote Expansion of Long-Term Engrafting Marrow Hematopoietic Stem and Progenitor Cells in Primates. Stem Cells Transl Med. 2017 Mar;6(3):864-876. doi: 10.5966/sctm.2016-0240. Epub 2016 Oct 14.
Results Reference
background
PubMed Identifier
29035282
Citation
Poulos MG, Ramalingam P, Gutkin MC, Llanos P, Gilleran K, Rabbany SY, Butler JM. Endothelial transplantation rejuvenates aged hematopoietic stem cell function. J Clin Invest. 2017 Nov 1;127(11):4163-4178. doi: 10.1172/JCI93940. Epub 2017 Oct 16.
Results Reference
background
PubMed Identifier
26441307
Citation
Poulos MG, Crowley MJP, Gutkin MC, Ramalingam P, Schachterle W, Thomas JL, Elemento O, Butler JM. Vascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis. Stem Cell Reports. 2015 Nov 10;5(5):881-894. doi: 10.1016/j.stemcr.2015.08.018. Epub 2015 Oct 1.
Results Reference
background
PubMed Identifier
9759811
Citation
Potter HG, Linklater JM, Allen AA, Hannafin JA, Haas SB. Magnetic resonance imaging of articular cartilage in the knee. An evaluation with use of fast-spin-echo imaging. J Bone Joint Surg Am. 1998 Sep;80(9):1276-84. doi: 10.2106/00004623-199809000-00005.
Results Reference
background
PubMed Identifier
25234349
Citation
Koff MF, Pownder SL, Shah PH, Yang LW, Potter HG. Ultrashort echo imaging of cyclically loaded rabbit patellar tendon. J Biomech. 2014 Oct 17;47(13):3428-32. doi: 10.1016/j.jbiomech.2014.08.018. Epub 2014 Sep 1.
Results Reference
background

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

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