Placebo-controlled Study to Evaluate Rexlemestrocel-L Alone or Combined With Hyaluronic Acid in Participants With Chronic Low Back Pain

NCT ID: NCT02412735

Last Updated: 2022-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 404 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-06
• Study Completion Date: 2021-06-15

Brief Summary

This is a prospective, multicenter, randomized, double-blind, placebo-controlled Phase 3 study designed to evaluate the safety and efficacy of Mesoblast's rexlemestrocel-L alone or combined with hyaluronic acid (HA) in participants with chronic low back pain (> 6 months) associated with moderate radiographic degenerative changes of a disc.

Conditions

Degenerative Disc Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Rexlemestrocel-L

Participants received rexlemestrocel-L 2.0 mL injection of approximately 6 million rexlemestrocel-L cells in freeze media mixed in a 1:1 by-volume ratio with saline on Day 0 (Visit 2).

Group Type: EXPERIMENTAL

Rexlemestrocel-L

Intervention Type: DRUG

Rexlemestrocel-L injection

Rexlemestrocel-L + HA

Participants received rexlemestrocel-L 2.0 mL injection of approximately 6 million rexlemestrocel-L cells in freeze media mixed in a 1:1 by-volume ratio with hyaluronic acid (HA) solution on Day 0 (Visit 2).

Group Type: EXPERIMENTAL

Rexlemestrocel-L + HA Mixture

Intervention Type: DRUG

Rexlemestrocel-L was combined in 1:1 by-volume ratio with HA solution and the resulting mixture was injected

Placebo

Participants received saline solution as matching-placebo on Day 0 (Visit 2).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Saline control solution

Interventions

Rexlemestrocel-L

Rexlemestrocel-L injection

Intervention Type: DRUG

Rexlemestrocel-L + HA Mixture

Rexlemestrocel-L was combined in 1:1 by-volume ratio with HA solution and the resulting mixture was injected

Intervention Type: DRUG

Placebo

Saline control solution

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male and female participants 18 years of age and older
• If female of childbearing potential, participant is non-pregnant, non-nursing, and agrees to use highly effective methods of contraception for a minimum of 24 months post-treatment
• Signed informed consent and country-appropriate privacy forms indicating participant is willing to undergo treatment and willing to be available for each examination scheduled over the study duration
• Have documented diagnosis of moderate radiographic degeneration of an intervertebral disc from L1 to S1, with a disc suspected of causing chronic low back pain (CLBP) associated with moderate radiographic degeneration at a lumbar disc is defined as the following (participant must meet all of the listed conditions):

1. Chronic low back pain for at least 6 months

2. Have failed 6 months of conservative back pain care. (Conservative treatment regimens may include any or all of the following: initial rest, medications [e.g., anti-inflammatory, analgesics, narcotics/opioids, muscle relaxants], massage, acupuncture, chiropractic manipulations, activity modification, home-directed lumbar exercise program, and non-invasive pain control treatments or procedures)

3. Have at a minimum undergone supervised physical therapy, such as daily walking routines, therapeutic exercises, and back education programs specifically for the treatment of low back pain and taken a pain medication for back pain (e.g. non-steroidal anti-inflammatory drug (NSAID) and/or opioid medication).

4. Change from normal disc morphology of the index disc as defined by radiographic evaluation by the core imaging evaluation provider. Radiographs must show all of the following:

• A modified Pfirrmann score of 3, 4, 5 or 6 on magnetic resonance imaging (MRI) at the index disc
• Modic Grade II changes or less on MRI at the index disc
• With or without contained disc protrusion at the index disc on MRI

e. Low back pain of at least 40mm and not more than 90mm of 100mm on low back pain visual analogue scale (VAS) (average pain over 24 hours)

f. Leg pain ≤20mm in both legs on a 100mm VAS scale

g. Oswestry disability index (ODI) score of at least 30 and no more than 90 on a 100 point scale.

Exclusion Criteria

• Female participants who are pregnant or nursing, or women planning to become pregnant in the first 24 months post-treatment
• Extreme obesity, as defined by National Institutes of Health (NIH) Clinical Guidelines Body Mass Index (BMI > 40)
• Have undergone a surgical procedure (e.g. discectomy, intradiscal electrothermal therapy, intradiscal radiofrequency, artificial disc replacement, interbody fusion) on the disc at the index or adjacent level
• Osteoporosis, as defined by dual-energy X-ray absorptiometry (DEXA) scan. A DEXA T-score of ≤ -2.5 will exclude the participant.
• Any lumbar intradiscal injection, including steroids, into the index or adjacent discs prior to treatment injection, with the exception of the following injections performed at least 2 weeks prior to study treatment:

1. Contrast medium (discography or other diagnostic injection)

2. NSAIDs

3. Nerve-blocking anesthetics (e.g., lidocaine, bupivacaine)

4. Antibiotics

5. Saline

• Have undergone a procedure affecting the structure/biomechanics of the index disc level (e.g., posterolateral fusion)
• Active malignancy or tumor as source of symptoms or history of malignancy within the 5 years prior to enrolment on study
• Have been a recipient of prior allogeneic stem cell/progenitor cell therapy for any indication or autologous stem cell/progenitor cell therapy or other biological intervention to repair the index intervertebral disc
• An average baseline morphine equivalent dose (MED) of >75mg/day as determined by e-diary entries during the screening period
• Taking systemic immunosuppressants
• A medical condition, serious intercurrent illness, or extenuating circumstance that would preclude participation in the study or potentially decrease survival or interfere with ambulation or rehabilitation.
• Participants involved in spinal litigation, including workman's compensation, unless litigation is complete
• Are transient or has a severe alcohol or substance abuse problem
• Clinically significant nerve pain (e.g., chronic radiculopathy or neuropathy)
• Clinically significant sacroiliac joint pain
• Compressive pathology due to stenosis or disc protrusion on MRI with associated clinical symptoms defined as leg pain VAS>20mm out of 100mm or neurologic deficit on neurologic exam
• Disc extrusion with a maximum dimension greater or equal to twice the posterior height of the disc, or disc sequestration in the lumbar spine on MRI as determined by radiographic core lab
• Modified Pfirrmann score of 7 or 8 at any lumbar level (L1-S1) on MRI evaluation as determined by radiographic core lab
• Symptomatic involvement of more than one lumbar disc
• Symptomatic central vertebral canal stenosis as defined by neurogenic claudication
• Spondylolisthesis or retrolisthesis Grade 2 and above or Spondylolysis at the index or adjacent level(s)
• Lumbar spondylitis or other undifferentiated spondyloarthropathy affecting the index disc
• Spinal deformity defined as lumbar scoliosis with a Cobb angle of the lumbar spine greater than 15 degrees
• Any fracture of the spine at the index or adjacent levels that has not healed, or clinically compromised vertebral bodies at the index level due to current or past trauma
• Facet pain at the index level or adjacent segments as determined by a diagnostic medial branch block (a facet block injection is not acceptable for making this determination) to rule out facet joint involvement.
• Full thickness annular tears in the index level as determined by free flowing contrast media through the annulus fibrosis.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Quintiles, Inc.

INDUSTRY

Sponsor Role: collaborator

Mesoblast, Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roger Brown

Role: STUDY_DIRECTOR

Mesoblast, Ltd.

Locations

Alabama Clinical Therapeutics, LLC

Birmingham, Alabama, United States

Tennessee Valley Pain Consultants

Huntsville, Alabama, United States

Arizona Pain Specialists

Scottsdale, Arizona, United States

Physicians Research Group

Tempe, Arizona, United States

TriWest Research Associates, LLC

El Cajon, California, United States

Memorial Orthopaedics Surgical Group

Long Beach, California, United States

Newport Beach Headache and Pain

Newport Beach, California, United States

Institute for Regenerative Medicine and Clinical Research

Pasadena, California, United States

UC Davis Spine Center

Sacramento, California, United States

Orthopedic Pain Specialists

Santa Monica, California, United States

The Spine Institute

Santa Monica, California, United States

Summit Pain Alliance

Santa Rosa, California, United States

Integrated Pain Management

Walnut Creek, California, United States

Denver Back Pain Specialists, LLC

Greenwood Village, Colorado, United States

George Washington University Medical Center

Washington D.C., District of Columbia, United States

Coastal Clinical Research Specialists

Fernandina Beach, Florida, United States

Shrock Orthopedic Research, LLC

Fort Lauderdale, Florida, United States

Holy Cross Orthopedics Institute

Oakland Park, Florida, United States

Emory Orthopaedics & Spine Center

Atlanta, Georgia, United States

Georgia Institute for Clinical Research, LLC

Marietta, Georgia, United States

Injury Care Medical Center

Boise, Idaho, United States

Millennium Pain Center

Bloomington, Illinois, United States

Otrimed Clinical Research

Edgewood, Kentucky, United States

Orthopedic Specialists of Louisiana

Shreveport, Louisiana, United States

Mayo Clinic

Rochester, Minnesota, United States

MAPS Applied Research Center

Shakopee, Minnesota, United States

Innovative Pain Care Center

Las Vegas, Nevada, United States

University Clinical Research

Somerset, New Jersey, United States

Ainsworth Institute of Pain Management

New York, New York, United States

Rochester Regional Health

Rochester, New York, United States

Carolina Neurosurgery and Spine Associates

Charlotte, North Carolina, United States

On Site Clinical Solutions, LLC

Morrisville, North Carolina, United States

The Center for Clinical Research/ Carolinas Pain Institute

Winston-Salem, North Carolina, United States

Cleveland Clinic

Cleveland, Ohio, United States

DOC Clinical Research

Dayton, Ohio, United States

Clinical Investigations, LLC

Edmond, Oklahoma, United States

Orthopaedic and Spine Specialists

York, Pennsylvania, United States

RI Hospital-Comprehensive Spine Center

Providence, Rhode Island, United States

Clinical Trials of South Carolina

Charleston, South Carolina, United States

Greenville Pharmaceutical Research, Inc.

Charleston, South Carolina, United States

Texas Back Institute

Plano, Texas, United States

Spine Team Texas

Southlake, Texas, United States

Precision Spine Care

Tyler, Texas, United States

Ericksen Research & Development, LLC

Bountiful, Utah, United States

the SMART Clinic

Draper, Utah, United States

Hope Research Institute

St. George, Utah, United States

Virginia iSpine Physicians, PC

Richmond, Virginia, United States

Monash Medical Center

Clayton, Victoria, Australia

Countries

United States; Australia

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MSB-DR003

Identifier Type: -

Identifier Source: org_study_id