Safety and Preliminary Efficacy Study of Mesenchymal Precursor Cells (MPCs) in Subjects With Lumbar Back Pain

• ClinicalTrials.gov Identifier: NCT01290367
• Recruitment Status: Completed
• First Posted: February 7, 2011
• Last Update Posted: June 26, 2020
• Sponsor: Mesoblast, Ltd.
• Information provided by (Responsible Party): Mesoblast, Ltd.

Study Description

Brief Summary:

The purpose of this study is to compare two doses of immunoselected, culture-expanded, nucleated, allogeneic adult MPCs when combined with hyaluronic acid to two control intradiscal injections in subjects with chronic low back pain due to moderate Degenerative Disc Disease (DDD) at one lumbar level from L1 to S1.

All investigational subjects in this study will undergo injection of either 6 million (M) or 18M cells in a hyaluronic acid carrier into the degenerated lumbar disc's nucleus pulposus. All control subjects will undergo an intradiscal control injection with either saline or hyaluronic acid only

Condition or disease	Intervention/treatment	Phase
Degenerative Disc Disease	Biological: Single Dose MPCs Injection; Procedure: Single injection of saline solution; Procedure: Single injection of hyaluronic acid	Phase 2

Detailed Description:

This is a prospective, multicenter, double blinded, controlled clinical study comparing two doses of immunoselected, culture-expanded, nucleated, allogeneic adult MPCs when combined with hyaluronic acid to two control intradiscal injections in subjects with chronic low back pain (> 6 months) due to moderate DDD at one lumbar level from L1 to S1 and unresponsive to conservative therapy for at least 3 months (including physical therapy).

After the screening and injection visits, each subject will be evaluated clinically and radiographically at 30 days, and again at 3, 6, 12, 24 and 36 months after injection.

Subjects will be evaluated at the same time points for safety.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Prospective, Double Blind, Controlled Study Evaluating Safety and Preliminary Efficacy of a Single Injection of Adult Mesenchymal Precursor Cells (MPCs) Combined With Hyaluronan in Subjects With Chronic Discogenic Lumbar Back Pain
• Study Start Date: August 2011
• Actual Primary Completion Date: July 2013
• Actual Study Completion Date: July 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: High Dose MPCs; Injection of High Dose MPCs with Hyaluronic Acid	Biological: Single Dose MPCs Injection; Injection of Low Dose MPCs with Hyaluronic Acid into the degenerated lumbar disc's nucleus pulposus.; Other Names: Direct MPCs Lumbar Disc Injection.; Stem Cells; Biological: Single Dose MPCs Injection; Injection of HighDose MPCs with Hyaluronic Acid into the degenerated lumbar disc's nucleus pulposus.; Other Name: Stem Cells
Experimental: Low Dose MPCs; Injection of Low Dose MPCs with Hyaluronic Acid	Biological: Single Dose MPCs Injection; Injection of Low Dose MPCs with Hyaluronic Acid into the degenerated lumbar disc's nucleus pulposus.; Other Names: Direct MPCs Lumbar Disc Injection.; Stem Cells; Biological: Single Dose MPCs Injection; Injection of HighDose MPCs with Hyaluronic Acid into the degenerated lumbar disc's nucleus pulposus.; Other Name: Stem Cells
Sham Comparator: Saline injection; Injection of saline solution.	Procedure: Single injection of saline solution; Intradiscal control injection with saline solution; Other Names: Saline injection; Sham control
Placebo Comparator: Hyaluronic acid injection; Injection of hyaluronic acid solution	Procedure: Single injection of hyaluronic acid; Intradiscal control injection with hyaluronic acid; Other Names: Hyaluronic acid injection; Vehicle control

Outcome Measures

Primary Outcome Measures :

1. To determine the overall safety of MPCs plus carrier using physical examinations, vital signs, treatment emergent adverse events (TEAEs), and the results of clinical lab tests (hematology, serum chemistry, inflammation, and immunology). [ Time Frame: 3 years ]

Secondary Outcome Measures :

1. To evaluate the change of treated lumbar intervertebral discs using Magnetic Resonance Imaging (MRI) at 6 months post injection of MPCs. [ Time Frame: 6 - 36 Months ]
2. To evaluate the effectiveness of MPCs in reducing chronic lumbar back pain using the visual analog scale (VAS). [ Time Frame: 1 - 36 Months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or females at least 18 years of age.
2. Have the ability to understand the requirements of the study, to provide written informed consent, and to comply with the study protocol.
3. Have the ability to understand and provide written authorization for the use and disclosure of personal health information (PHI) [per Health Insurance Portability and Accountability Act (HIPAA) privacy ruling in the US].
4. Have chronic low back pain for at least 6 months.
5. Have documented symptomatic diagnosis of DDD of one level from L1-S1 as determined by a change in disc hydration on MRI compared to normal disc with or without an annular fissure or a contained disc herniation.
6. Have failed 3 months of non-operative low back pain management.
7. Disc height loss of <30% compared to a normal adjacent disc based upon radiographic evaluation.
8. Pre-treatment baseline low back pain of at least 40 mm on a 100 mm visual analog scale.
9. Low back pain greater than leg pain.
10. Pre-treatment baseline Oswestry Disability Index Questionnaire score of at least 30 on the 100-point questionnaire.

Exclusion Criteria:

1. Female subjects who are pregnant or nursing, or women planning to become pregnant during the first year (12 months) following surgery.
2. Have a current or prior history within the last 3 years of neoplasm (excluding basal cell carcinoma) and/or any active neoplasm within the last 24 months, prior to screening.
3. Patients with compressive pathology due to stenosis or frankly herniated disc or sequestered discs are not candidates.
4. Intact disc bulge/protrusion or focal herniation at the symptomatic level (s) > 3 mm or presence of disc extrusion or sequestration.
5. Lumbar spondylitis or other undifferentiated spondyloarthropathy.
6. Have undergone a previous surgery at the involved levels.
7. Any lumbar intradiscal injection procedure (e.g., injection of corticosteroids, methylene blue, dextrose, or glucosamine and chondroitin sulfate). Discography may be performed, but must be done at least 2 weeks or more prior to the MPC injection procedure.
8. Have an acute fracture of the spine at the time of enrollment in the study.
9. Have a history of epidural steroid injections within 1 week prior to study treatment.
10. Have a known history of hypersensitivity or anaphylactic reaction to murine or bovine products or dimethyl sulfoxide (DMSO).
11. Have a positive screen for human immunodeficiency virus (HIV) antibodies.
12. Have a known history of hypersensitivity or anaphylactic reaction to Hyaluronan.
13. Have a current or prior history within the last 3 years of neoplasm (excluding basal cell carcinoma) and/or any active neoplasm within the last 24 months, prior to screening.
14. Have been a recipient of prior stem cell/progenitor cell therapy or other biological intervention to repair the target intervertebral disc.
15. Are transient or has been treated in the last 6 months before enrollment for alcohol and/or drug abuse in an inpatient substance abuse program.
16. Currently incarcerated (prisoners).

Contacts and Locations

Locations

United States, Arizona

Arizona Pain Specialists

Scottsdale, Arizona, United States, 85258

United States, California

UC Davis Spine Center

Sacramento, California, United States, 95816

The Spine Institute

Santa Monica, California, United States, 90403

IPM Medical Group, Inc.

Walnut Creek, California, United States, 94598

United States, Colorado

Denver Spine

Denver, Colorado, United States, 80111

Rocky Mountain Associates in Orthopedic Medicine, P.C.

Loveland, Colorado, United States, 80538

United States, Georgia

Emory University School of Medicine

Atlanta, Georgia, United States, 30329

United States, North Carolina

Carolina Neurosurgery and Spine Associates

Charlotte, North Carolina, United States, 28204

United States, Texas

Central Texas Spine Institute

Austin, Texas, United States, 78731

Richmond Bone and Joint Clinic, Memorial Hermann Medical Group

Richmond, Texas, United States, 77469

United States, Virginia

Virginia Spine Research Institute, Inc.

Richmond, Virginia, United States, 23235

United States, Washington

Washington Center for Pain Management

Edmonds, Washington, United States, 98026

United States, West Virginia

The Center for Pain Relief, Inc.

Charleston, West Virginia, United States, 25301

Australia, Victoria

Monash Medical Center

Clayton, Victoria, Australia, 3168

Sponsors and Collaborators

Mesoblast, Ltd.

Investigators

• Study Director: Roger Brown; Mesoblast, Ltd.

More Information

• Responsible Party: Mesoblast, Ltd.
• ClinicalTrials.gov Identifier: NCT01290367
• Other Study ID Numbers: MSB-DR001
• First Posted: February 7, 2011
• Last Update Posted: June 26, 2020
• Last Verified: June 2020

Keywords provided by Mesoblast, Ltd.:

Chronic Lumbar Back Pain; Low back pain; Back pain; Degenerative Disc Disease; Injection of Degenerated Lumbar Disc; Stem Cells; Adult Stem Cells; Allogeneic Mesenchymal Precursor cells (MPCs); Mesoblast

Additional relevant MeSH terms:

Intervertebral Disc Degeneration; Back Pain; Low Back Pain; Pain; Neurologic Manifestations; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Hyaluronic Acid; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs; Viscosupplements; Protective Agents