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

NCT02412735 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: MSB-DR003
• Study Type: interventional
• Target: 404
• Locations: 2 countries
• Sites: 48

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

Keywords

Chronic Lumbar Back Pain; Low back pain; Back pain; Degenerative Disc Disease; Injection of Degenerated Lumbar Disc; Intervertebral Disc Degeneration; Bone Diseases; Musculoskeletal Diseases; Nervous System Diseases; Neurologic Manifestations; Pain; Spinal Diseases; Stem Cells; Adult Stem Cells; Allogeneic Mesenchymal Precursor cells (MPCs); Mesoblast; Hyaluronic Acid; Pharmaceutical Solutions; Adjuvants, Immunologic; Immunologic Factors; Pharmacologic Actions; Protective Agents; rexlemestrocel-L; Viscosupplements

Outcome Measures

Primary Outcomes (1)

• Overall Treatment Success: Bayesian Estimated Response Rate

  Overall treatment success was determined based on number of responders who had composite response at both months 12 and 24 evaluated per specified criteria. A treatment responder with treatment success was defined as a participant who met the 3 criteria of a composite responder analysis as: 50% or greater reduction in the lower-back pain visual analogue scale (VAS) score; 15-point or greater reduction in the Oswestry Disability Index (ODI) score; and lack of post-treatment interventions at the treated level as of the study visit (Visits 6 \[12 months post-treatment\] and 8 \[24 months post-treatment\]). The average response rate (proportion of participants with response presented as Bayesian estimate\[BE\]) was based upon the average of multiple Bayesian simulations.

  Up to 24 months

Secondary Outcomes (6)

• Effectiveness Based on Pain Responders: Bayesian Estimated Response Rate

  Up to 24 months

• Effectiveness Based on Functional Responders: Bayesian Estimated Response Rate

  Up to 24 months

• Effectiveness Based on Treatment Success at 24 Months: Bayesian Estimated Response Rate

  Month 24

• Effectiveness Based on Minimal Pain Responders at 24 Months: Bayesian Estimated Response Rate

  Month 24

• Effectiveness Based on Time to First Intervention Over 24 Months

  Up to Month 24

Other Outcomes (1)

• Mean Change From Baseline in Low Back Pain Visual Analog Scale (VAS) Score at 1, 3, 6, 12, 18, 24, and 36 Months

  Months 1, 3, 6, 12, 18, 24, and 36

Study Arms (3)

Rexlemestrocel-L

EXPERIMENTAL

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).

Drug: Rexlemestrocel-L

Rexlemestrocel-L + HA

EXPERIMENTAL

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).

Drug: Rexlemestrocel-L + HA Mixture

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Rexlemestrocel-L DRUG

Rexlemestrocel-L injection

Rexlemestrocel-L

Rexlemestrocel-L + HA Mixture DRUG

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

Rexlemestrocel-L + HA

Placebo DRUG

Saline control solution

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• Chronic low back pain for at least 6 months
• 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)
• 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).
• 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.

You may not qualify if:

• 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:
• Contrast medium (discography or other diagnostic injection)
• NSAIDs
• Nerve-blocking anesthetics (e.g., lidocaine, bupivacaine)
• Antibiotics
• 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

Sponsors & Collaborators

• Mesoblast, Ltd.: lead
• Quintiles, Inc.: collaborator

Study Sites (48)

Alabama Clinical Therapeutics, LLC

Birmingham, Alabama, 35235, United States

Location

Tennessee Valley Pain Consultants

Huntsville, Alabama, 35801, United States

Location

Arizona Pain Specialists

Scottsdale, Arizona, 85258, United States

Location

Physicians Research Group

Tempe, Arizona, 85284-2604, United States

Location

TriWest Research Associates, LLC

El Cajon, California, 92020-4124, United States

Location

Memorial Orthopaedics Surgical Group

Long Beach, California, 90806, United States

Location

Newport Beach Headache and Pain

Newport Beach, California, 92660, United States

Location

Institute for Regenerative Medicine and Clinical Research

Pasadena, California, 91105, United States

Location

UC Davis Spine Center

Sacramento, California, 95816, United States

Location

Orthopedic Pain Specialists

Santa Monica, California, 90403, United States

Location

The Spine Institute

Santa Monica, California, 90403, United States

Location

Summit Pain Alliance

Santa Rosa, California, 95401, United States

Location

Integrated Pain Management

Walnut Creek, California, 94598, United States

Location

Denver Back Pain Specialists, LLC

Greenwood Village, Colorado, 80111, United States

Location

George Washington University Medical Center

Washington D.C., District of Columbia, 20037, United States

Location

Coastal Clinical Research Specialists

Fernandina Beach, Florida, 32034, United States

Location

Shrock Orthopedic Research, LLC

Fort Lauderdale, Florida, 33316, United States

Location

Holy Cross Orthopedics Institute

Oakland Park, Florida, 33334, United States

Location

Emory Orthopaedics & Spine Center

Atlanta, Georgia, 30329, United States

Location

Georgia Institute for Clinical Research, LLC

Marietta, Georgia, 30060, United States

Location

Injury Care Medical Center

Boise, Idaho, 83713, United States

Location

Millennium Pain Center

Bloomington, Illinois, 61701, United States

Location

Otrimed Clinical Research

Edgewood, Kentucky, 41017, United States

Location

Orthopedic Specialists of Louisiana

Shreveport, Louisiana, 71103, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MAPS Applied Research Center

Shakopee, Minnesota, 55379, United States

Location

Innovative Pain Care Center

Las Vegas, Nevada, 89129, United States

Location

University Clinical Research

Somerset, New Jersey, 08873, United States

Location

Ainsworth Institute of Pain Management

New York, New York, 10022, United States

Location

Rochester Regional Health

Rochester, New York, 14626, United States

Location

Carolina Neurosurgery and Spine Associates

Charlotte, North Carolina, 28204, United States

Location

On Site Clinical Solutions, LLC

Morrisville, North Carolina, 28117, United States

Location

The Center for Clinical Research/ Carolinas Pain Institute

Winston-Salem, North Carolina, 27103, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44106, United States

Location

DOC Clinical Research

Dayton, Ohio, 45432, United States

Location

Clinical Investigations, LLC

Edmond, Oklahoma, 73013, United States

Location

Orthopaedic and Spine Specialists

York, Pennsylvania, 17402, United States

Location

RI Hospital-Comprehensive Spine Center

Providence, Rhode Island, 02903, United States

Location

Clinical Trials of South Carolina

Charleston, South Carolina, 29406, United States

Location

Greenville Pharmaceutical Research, Inc.

Charleston, South Carolina, 29406, United States

Location

Texas Back Institute

Plano, Texas, 75093, United States

Location

Spine Team Texas

Southlake, Texas, 76092, United States

Location

Precision Spine Care

Tyler, Texas, 75701, United States

Location

Ericksen Research & Development, LLC

Bountiful, Utah, 84010, United States

Location

the SMART Clinic

Draper, Utah, 84020, United States

Location

Hope Research Institute

St. George, Utah, 84790, United States

Location

Virginia iSpine Physicians, PC

Richmond, Virginia, 23235, United States

Location

Monash Medical Center

Clayton, Victoria, 3168, Australia

Location

MeSH Terms

Conditions

Intervertebral Disc Degeneration; Low Back Pain; Back Pain; Bone Diseases; Musculoskeletal Diseases; Nervous System Diseases; Neurologic Manifestations; Pain; Spinal Diseases

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Christopher James, VP Head of Clinical Operations
• Organization: Mesoblast, Inc.

Christopher.James@Mesoblast.com

212-880-2060

Study Officials

• Roger Brown

  Mesoblast, Ltd.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2015
• First Posted: April 9, 2015
• Study Start: March 6, 2015
• Primary Completion: May 15, 2020
• Study Completion: June 15, 2021
• Last Updated: October 19, 2022
• Results First Posted: January 18, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); US (47)