Autologous Adult Adipose-Derived Regenerative Cell Injection Into Chronic Partial-Thickness Rotator Cuff Tears

A Prospective, Double-Blinded, Multi-Center Pivotal Trial of Autologous Adult Adipose-Derived Regenerative Cell Injection Into Chronic Partial-Thickness Rotator Cuff Tears

The purpose of this investigation is to evaluate the safety and superior effectiveness in functional improvement in patients with partial-thickness rotator cuff tears (PTRCTs) after the administration of a single injection of adipose-derived regenerative cells (ADRCs) into the partial-thickness rotator cuff tear compared to the administration of a single corticosteroid injection into the associated subacromial space.

Study Overview

• Status: Active, not recruiting
• Conditions: Rotator Cuff Tear; Rotator Cuff Tendinitis
• Intervention / Treatment: Device: Adipose Derived Regenerative Cells; Drug: Corticosteroid

Detailed Description

This is a prospective, double-blinded, randomized, active-controlled, multi-site, pivotal safety and superior effectiveness study in patients with symptomatic partial-thickness rotator cuff tears comparing a single ADRC injection generated with the Transpose® RT system into the supraspinatus tendon and surrounding area to standard-of-care (SOC) corticosteroid injection into the subacromial bursa.

Up to 20 U.S. centers will be initiated to enroll in the study. 246 subjects assigned to two randomization arms will be enrolled: an adipose-derived regenerative cell (ADRC) injection arm (ADRC treatment arm) and the SOC corticosteroid injection arm (active control arm). All subjects will be randomly assigned to ADRC treatment or active control arms in a 2:1 ratio.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Arizona Research Center
  • California
    • La Mesa, California, United States, 91942
      • Biosolutions Clinical Research Center
    • Pasadena, California, United States, 91105
      • Lotus Clinical Research, LLC
  • Florida
    • Coral Springs, Florida, United States, 33067
      • Sports and Orthopedic Center
    • Doral, Florida, United States, 33166
      • Universal Axon Clinical Research
    • Fort Lauderdale, Florida, United States, 33316
      • Shrock Clinical Research
    • Gulf Breeze, Florida, United States, 32561
      • Andrews Institute for Orthopaedics and Sports Medicine
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Georgia Institute for Clinical Research
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • University of Michigan
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Sanford Medical Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Orthopedic Clinic/Research
  • Texas
    • Houston, Texas, United States, 77041
      • HD Research
    • San Antonio, Texas, United States, 78240
      • Texas Plastic Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Males and females 30-75 years of age (inclusive).
2. Subjects have a minimum of three (3) months of clinical symptoms consistent with a partial-thickness rotator cuff tear including but not limited to pain, muscle weakness, or limited active range of motion (AROM).
3. Subjects have > 70% passive range of motion (PROM) of the index shoulder.
4. Subjects have a baseline VAS - Pain score of ≥ 30 mm.
5. Subjects have a partial-thickness rotator cuff tear, defined as ≥25% partial-thickness tear of the supraspinatus tendon on a 1.5 Tesla (1.5T) or a 3 Tesla (3T) MRI within the last 3 months, as determined by the Investigator.
6. Subjects can give appropriate consent.

Exclusion Criteria:

1. Age < 30 or > 75.
2. Subject has an insufficient amount of subcutaneous tissue to allow recovery of 100 milliliters (mL) of adipose tissue.
3. Subjects who have received a corticosteroid injection in the index subacromial bursa within the last 3 months.
4. Subjects who have received more than one (1) previous corticosteroid injections or any biologic treatment in the index subacromial bursa within the past 6 months.
5. Subjects with severe arthrosis of the glenohumeral or acromioclavicular joint.
6. Subjects with a full-thickness tear of the rotator cuff.

7. Subjects who have undergone major surgery on the affected shoulder meeting one of the following criteria:

   • Performed as treatment for (or required manipulation of) the rotator cuff. Examples include, but are not limited to, subacromial decompression, rotator cuff repair, SLAP repair, arthroplasty and fracture fixation with implants that involve or penetrate the rotator cuff; OR
   • Performed using implants that interfere with MR visualization and/or evaluation of the supraspinatus tendon (e.g., biceps tenodesis); OR
   • Performed in/on the glenohumeral joint, subacromial space, or acromioclavicular joint within the last 3 years (e.g. soft tissue Bankart repairs performed >3 years ago may still qualify).

   NOTE: This exclusion criterion does not apply to minor soft tissue procedures with short recovery periods that do not involve musculoskeletal structures (e.g., lipoma excision).

8. Subjects who were diagnosed with or treated for adhesive capsulitis of the index shoulder within the last 5 years.
9. Subjects with current cervical radiculopathy impacting the index shoulder.
10. Subjects who require the use of index arm for ambulation or mobilization via wheelchair, walker, crutches or cane.
11. Subjects with any contraindication to MRI scan according to MRI guidelines, or who are unwilling to undergo MRI procedures.
12. Subjects whose pain behavior or pain medication usage is, in the opinion of the Investigator, out of proportion to the underlying clinical condition or could interfere with the study- required assessments.
13. Subjects with a history of systemic malignant neoplasms within the last 5 years.
14. Subjects with biopsy-proven, malignant or local neoplasm within the last 6 months or any history of local neoplasm at the site of administration (on the affected arm), excluding basal cell carcinoma.
15. Subject is receiving immunosuppressant therapy or has a known immunologic or severe autoimmune disease that requires chronic systemic immunosuppressive or immunomodulatory therapy (e.g., human immunodeficiency virus, systemic lupus erythematosus, rheumatoid arthritis, etc.). [Note: Topical or inhaled corticosteroids are permitted.]
16. Subject is on an active regimen of chemotherapy or radiation- based treatment.
17. Subjects with an allergy to sodium citrate or any "caine" type of local anesthetic.
18. Subject is pregnant or breastfeeding or plans to become pregnant in the next 12 months.
19. Subjects with clinically significant abnormal Lab tests (i.e. basic metabolic panel (BMP) or equivalent (e.g. CHEM-7), complete blood count (CBC), Liver function tests (LFTs), and prothrombin time/international normalized ratio (PT/INR)) as interpreted by the Investigator.

21. Subjects with a history of a bleeding diathesis or coagulopathy

22. Subject is, in the opinion of the Investigator, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason. Examples include the inability of the subject to complete patient-reported outcome instruments (PROs) and the inability of the Investigator to perform the injection procedure properly because of anatomic limitations of the subject.

23. Subject is currently participating in another clinical trial that has not yet completed its primary endpoint. (Noninterventional observational studies are not exclusionary.)

24. Subject 1) is a litigant in a civil suit that could affect the subject's ability to complete the study related activities or 2) is a defendant in a criminal case or 3) has an active workman's compensation case in progress.

25. Subject is part of a vulnerable population who, in the judgment of the Investigator, is unable to give informed consent for reasons of incapacity, immaturity, adverse personal. circumstances or lack of autonomy. This may include: individuals with a mental disability, persons in nursing homes, children, impoverished persons, persons in emergency situations, homeless persons, nomads, refugees, and those incapable of giving informed consent. Vulnerable populations also may include members of a group with a hierarchical structure such as university students, subordinate hospital and laboratory personnel, employees of the Sponsor, members of the armed forces, and persons kept in detention.

26. Uncooperative subjects or those with neurological/psychiatric disorders who are incapable of following directions or who are predictably unwilling to return for follow-up examinations.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adipose Derived Regenerative Cells; Adipose-derived regenerative cell injection into the area of the supraspinatus tendon tear	Device: Adipose Derived Regenerative Cells; Adipose-derived regenerative cells isolated with the Transpose Ultra system
Active Comparator: Corticosteroid; Subjects in the active control arm will receive a corticosteroid injection into the subacromial space using ultrasound (US) guidance.	Drug: Corticosteroid; Corticosteroid injection into subacrominal space

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in Pain: VAS	≥ 14-millimeter (mm) improvement in Visual Analog Scale (VAS)	24 weeks
Improvement or no worsening in supraspinatus strength	supraspinatus strength on the MRC Muscle Scale compared to baseline For supraspinatus strength on the MRC Muscle Scale compared to baseline • For subjects with normal supraspinatus strength (MRC Muscle Scale = 5] at baseline: no worsening in supraspinatus strength on the MRC Muscle Scale compared to baseline	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects who demonstrate ≥ 14 mm improvement in VAS	Pain score compared to baseline at 24 weeks	24 weeks
Percentage of subjects who demonstrate improvement or no worsening of supraspinatus strength on the MRC Muscle Scale	Supraspinatus strength on the MRC Muscle Scale compared to baseline at 24 weeks	24 weeks
Mean improvement in VAS - Pain score	VAS pain score compared to baseline	12 and 24 weeks
Mean improvement in WORC score	WORC score compared to baseline	12 and 24 weeks
Percentage of subjects who demonstrate a ≥ 1-grade improvement in supraspinatus strength on the MRC Muscle Scale	Supraspinatus strength on the MRC Muscle Scale compared to baseline at 24 weeks.	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean improvement in Rand Short Form-36 score	Rand Form-36 score compared at baseline	24 weeks
Measurement of subject satisfaction with treatment on a VAS scale (VAS - Satisfaction)	VAS satisfaction score improvement	24 weeks
Measurement of EuroQoL-5D-5L (EQ-5D-5L)	EuroQoL -5D-5L score	24 weeks
Measurement of Shoulder Activity Level	Recording shoulder activity level	24 weeks
Measurement of shoulder motion (forward elevation, shoulder abduction in the plane of the scapula)	As determined by goniometer	24 weeks

Collaborators and Investigators

• Sponsor: InGeneron, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2019
• Primary Completion (Actual): November 30, 2023
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: November 20, 2018
• First Submitted That Met QC Criteria: November 23, 2018
• First Posted (Actual): November 26, 2018

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: rotator cuff tear; corticosteroid; adipose-derived regenerative cells; adipose-derived stem cells; partial rotator cuff tears
• Additional Relevant MeSH Terms: Wounds and Injuries; Musculoskeletal Diseases; Muscular Diseases; Rupture; Shoulder Injuries; Tendon Injuries; Rotator Cuff Injuries; Tendinopathy
• Other Study ID Numbers: RC-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes