Study to Evaluate the Safety and Efficacy of AM3101 to Augment Meniscal Healing

Официальное название

A Prospective, Randomized, Controlled, Double-Blinded, Multi-Center, Phase 1/2b Study to Evaluate the Safety and Efficacy of AM3101 to Augment Meniscal Healing

Обзор

The purpose of this clinical trial is to assess the safety and efficacy of AM3101 to facilitate meniscal repair and reduce the incidence of non-healing complications and morbidities associated with a failed meniscal repair. This is a prospective, randomized, controlled, double-blinded, multi-center study.

Подробное описание

Primary Efficacy Objective: Assess the efficacy of AM3101 by evaluating the integrity of repaired meniscal tissue assessed via MRI at 12 months following injection with AM3101 as compared to the integrity of meniscal tissue at 12 months in the control group injected with a saline solution (placebo).

Primary Safety Objective: Assess the safety of AM3101 by evaluating the incidence of individual adverse events and comparing these adverse event rates to incidence rates for the control group injected with a saline solution (placebo).

Secondary Objective: Assess and compare functional outcomes in patients receiving AM3101 following meniscal repair to functional outcomes in the control group injected with a saline solution (placebo).

Вмешательства

• Препарат AM3101
  Injectable drug product.
• Препарат Saline Placebo
  2 mL 0.9% normal saline

Первичные конечные точки

• Healing Assessed via MRI [Срок оценки: 12 months]
• Incidence of Adverse Events [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Male or female ≥ 18 and ≤ 40 years old at time of screening.
• MRI evidence of ACL plus meniscus tear, or isolated meniscus tear.
• Body mass index (BMI) ≤ 40 kg/m2.
• Liver and kidney function panels within normal ranges at time of screening
• Willing and able to comply with the study procedures and visit schedule, and able to follow oral and written instructions.
• Willing and able to sign an IRB approved informed consent

Критерии исключения

• Have any concomitant ligament injury requiring surgical repair or reconstruction other than the ACL.
• Have a history of previous meniscus injury that currently needs to be treated or has been treated surgically.
• Have evidence of arthritis ≥ Grade III (Outerbridge classification) in the affected compartment or greater than Kellgren Lawrence Grade 3.
• Elevated AST or ALT liver enzymes at time of screening
• Pregnant or nursing mothers, or women planning on getting pregnant during the time they will be participating in the study.
• Known drug or alcohol dependence currently or within the last year.
• Participating concurrently in another clinical study or have participated in a clinical study within the last 90 days, or intend to during the course of the study.
• Any medical condition or other circumstances that might interfere with the ability to return for follow-up visits in the judgment of the Investigator, including any systemic illness, neuromuscular, neurosensory, or musculoskeletal deficiency that would render the subject unable to perform appropriate postoperative rehabilitation.
• Any condition which, in the judgment of the Investigator, would preclude adequate evaluation of the investigational product's safety and efficacy.
• Known allergic reaction to simvastatin.
• Patients currently taking simvastatin, or any other drug that is within the statin drug classification family.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 3 центра

• University of Cincinnati — Cincinnati
• University Hospitals Cleveland Medical Center — Cleveland
• Oregon Health & Science University — Portland

Публикации

• Nepple JJ, Dunn WR, Wright RW. Meniscal repair outcomes at greater than five years: a systematic literature review and meta-analysis. J Bone Joint Surg Am. 2012 Dec 19;94(24):2222-7. doi: 10.2106/JBJS.K.01584. PMID 23318612
• Xu H, Bouta EM, Wood RW, Schwarz EM, Wang Y, Xing L. Utilization of longitudinal ultrasound to quantify joint soft-tissue changes in a mouse model of posttraumatic osteoarthritis. Bone Res. 2017 Jun 13;5:17012. doi: 10.1038/boneres.2017.12. eCollection 2017. PMID 28638676
• Proulx ST, Kwok E, You Z, Papuga MO, Beck CA, Shealy DJ, Ritchlin CT, Awad HA, Boyce BF, Xing L, Schwarz EM. Longitudinal assessment of synovial, lymph node, and bone volumes in inflammatory arthritis in mice by in vivo magnetic resonance imaging and microfocal computed tomography. Arthritis Rheum. 2007 Dec;56(12):4024-37. doi: 10.1002/art.23128. PMID 18050199
• Fukui T, Ii M, Shoji T, Matsumoto T, Mifune Y, Kawakami Y, Akimaru H, Kawamoto A, Kuroda T, Saito T, Tabata Y, Kuroda R, Kurosaka M, Asahara T. Therapeutic effect of local administration of low-dose simvastatin-conjugated gelatin hydrogel for fracture healing. J Bone Miner Res. 2012 May;27(5):1118-31. doi: 10.1002/jbmr.1558. PMID 22275312
• Oka S, Matsumoto T, Kubo S, Matsushita T, Sasaki H, Nishizawa Y, Matsuzaki T, Saito T, Nishida K, Tabata Y, Kurosaka M, Kuroda R. Local administration of low-dose simvastatin-conjugated gelatin hydrogel for tendon-bone healing in anterior cruciate ligament reconstruction. Tissue Eng Part A. 2013 May;19(9-10):1233-43. doi: 10.1089/ten.TEA.2012.0325. Epub 2013 Jan 14. PMID 23198912
• Vos LM, Kuijer R, Huddleston Slater JJ, Bulstra SK, Stegenga B. Inflammation is more distinct in temporomandibular joint osteoarthritis compared to the knee joint. J Oral Maxillofac Surg. 2014 Jan;72(1):35-40. doi: 10.1016/j.joms.2013.08.022. Epub 2013 Nov 6. PMID 24210930
• Donahue RP, Gonzalez-Leon EA, Hu JC, Athanasiou K. Considerations for translation of tissue engineered fibrocartilage from bench to bedside. J Biomech Eng. 2018 Dec 5;141(7):0708021-07080216. doi: 10.1115/1.4042201. Online ahead of print. PMID 30516244
• Roy TC. Diagnoses and mechanisms of musculoskeletal injuries in an infantry brigade combat team deployed to Afghanistan evaluated by the brigade physical therapist. Mil Med. 2011 Aug;176(8):903-8. doi: 10.7205/milmed-d-11-00006. PMID 21882780

Идентификаторы

NCT: NCT05560477 · Protocol Number: SM17091 · UC IRB Number: 2019-0468

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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