Utilization of Autologous Mesenchymal Cells in Posterolateral Spinal Fusion in Degenerative Spine Disease (AMSC-DSD-001)

Utilization of Autologous Mesenchymal Cells in Posterolateral Spinal Fusion in Degenerative Spine Disease to Assess the Safety and the Efficacy

Subjects in whom a posterolateral fusion surgery has been planned and who meet the inclusion and exclusion criteria were proposed to receive a single-dose AMSC treatment, in order to assess its safety and efficacy on posterolateral interbody fusion. After the surgery, the subjects were followed up as out-patients during 5 study visits for 12 months in total.

Study Overview

• Status: Terminated
• Conditions: Degenerative Disc Disease
• Intervention / Treatment: Drug: Suspension of human autologous MSC 3P in 1.5 ml

Detailed Description

Following informed consent collection at the screening visit and verification of all inclusion and exclusion criteria, eligible patients will undergo the procedure of bone marrow cell aspiration from iliac crest for the purpose of receiving autologous multipotent mesenchymal stem cells. The cells will be cultivated for 3 passages (for 3 - 4 weeks) in order to expand them to sufficient quantity. Suspension of the cultured AMSC will then be sterilely packed and transported to the surgery site. During the posterolateral spine fusion operation, 1.5 ml of cell suspension will be mixed with 5 cc of beta-tricalcium phosphate foam (Vitoss™, Orthovita) and 3.5 ml of patient's blood, and inserted between the transverse processes of the lumbar spine.

All subjects will be hospitalized and followed up as per standard medical care rules used in the investigational site hospital for this type of intervention.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. established diagnosis of spinal degenerative disease indicated for lumbar spine surgery,
2. patients indicated for fusion therapy,
3. patients between 18-55 years, both sexes,
4. patients able to provide written informed consent.

Exclusion Criteria:

1. previous lumbar spine surgery in the same segment of the spine, in order to achieve vertebral fusion,
2. osteoporosis,
3. diabetes mellitus,
4. pregnancy or breastfeeding,
5. women of childbearing potential not using effective contraception (established oral contraception, intrauterine device, ligation of the uterine tube) including proven contraceptive measures taken by their sexual partners,
6. fertile men not using proven contraceptive measures including effective contraception method in their partner (established oral contraception, intrauterine device, ligation of the uterine tube),
7. coagulopathy,
8. malnutrition, primary biliary cirrhosis,
9. skin infection at the site of bone marrow aspiration or at the site of spinal fusion,
10. gastrostomy,
11. any significant medical condition that would compromise the safety of the patient (e.g. recent myocardial infarction, congestive heart failure, renal failure, liver failure, systemic infection, recurrent thromboembolic disease .....),
12. alcohol or drug abuse,
13. cancer (compulsory clinical oncological screening),
14. ongoing or recent (last 3 months) systemic corticosteroid or immunosuppressive therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Human AMSC (passage 3) 3P in 1.5 mL; Patient receiving the investigational medicinal product - suspension of human autologous MSC 3P in 1.5 mL	Drug: Suspension of human autologous MSC 3P in 1.5 ml; During the posterolateral spine fusion operation, 1.5 ml of cell suspension was mixed with 5cc of beta-tricalcium phosphate foam and 3.5 ml of patient's blood, and inserted between the right transverse processes of the lumbar spine.; Other Names: hAMSC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: To demonstrate absence of complications at the site of spinal fusion	Complications at the site of spinal fusion and other treatment-related adverse events will be recorded in ten patients at Visits I through VII. All adverse events (AEs) will be classified by seriousness, severity and relationship to hAMSC application. All AEs will be collected as symptoms spontaneously reported by the patient, clinically relevant changes and abnormalities observed by the Investigator (clinically significant laboratory measurements confirmed by repeated measurement, results of physical examinations) Intensity The following 3-point rating scale will be used for rating of the intensity of each AE: Mild: Awareness of signs or symptoms, but no disruption of usual activity Moderate: Event sufficient to affect usual activities (disturbing) Severe: Inability to work or perform usual activities (unacceptable)	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: To assess the quality of life determined by Oswestry Questionnaire.	The quality of life determined by Oswestry Questionnaire will be recorded in ten patients at Visits II, and IV through VII. The test has 10 sections and maximum score is 50 points; change from the baseline valie will be recorded. The points are then transferred into percentage and interpreted in a standard way when 0-20% means minimal disability while 81-100% means bed-bound condition. Minimum detectable change (90 % confidence) is 10 % (5 points).	1 year
Efficacy: To assess the quality of spinal fusion by X-ray imaging	The quality of spinal fusion will be measured by X-ray imaging at Visits V and VII. Dynamic X-ray of the lumbar spine will be performed at 3 and 12 months following the surgery and hAMSC application to measure the angle of the spine movement in the fusion area. The angle will be recorded in degrees. The movements above 10 degrees will beregarded as "unstable". The bone fusion morphology will be evaluated based on the following scale: Cyst or pseudo-cyst formation; Fusion not visible; Pseudo-joint (or false joint) development; Low degree of bone fusion; High degree of bone fusion	1 year
Efficacy: To assess the quality of spinal fusion measured by computed tomography (CT).	The quality of spinal fusion will be measured by CT in ten patients at Visits V and VII. The density will of the fusion will be expressed as % on a linear scale between two standardized measuring points: soft tissue= 0%, vertebral arch= 100%.	1 year

Collaborators and Investigators

• Sponsor: Bioinova, s.r.o.
• Collaborators: Department of Spine Surgery, University Hospital Motol, Prague, Czech Republilc

Study record dates

Study Major Dates

• Study Start (Actual): August 27, 2013
• Primary Completion (Actual): December 14, 2016
• Study Completion (Actual): December 14, 2016

Study Registration Dates

• First Submitted: January 14, 2019
• First Submitted That Met QC Criteria: January 31, 2019
• First Posted (Actual): February 1, 2019

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 14, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Spinal Diseases; Bone Diseases; Intervertebral Disc Degeneration
• Other Study ID Numbers: AMSC-DSD-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data will be published

Drug and device information, study documents

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