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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат E-CEL UVEC
  Local implantation of E-CEL UVEC cells at the supraspinatus tendon repair site

Первичные конечные точки

• Short-term safety [Срок оценки: 0 surgery to +11 days post op]

Вторичные конечные точки (4)

• Long-term safety [Срок оценки: post-operative 90 day to 1 year following the surgical repair]
• MRI [Срок оценки: post-operative 90 day to 1 year]
• Strength [Срок оценки: post-operative 90 day to 1 year]
• PROMS [Срок оценки: post-operative 90 day to 1 year]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Hospital for Special Surgery — New York

Публикации

• 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. PMID 20436053
• 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. PMID 6991502
• 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. PMID 26635616
• 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. PMID 26188783
• 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. PMID 17574875
• 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. PMID 22709690
• 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. PMID 21068842
• 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. PMID 22036563

Идентификаторы

NCT: NCT04057833 · 2018-0809

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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