Efficacy and Safety of Rexlemestrocel-L Combined With HA* in Participants With Moderate to Severe Chronic Low Back Pain (HyaluronicAcid)

A Prospective, Multicenter, Randomized, Double-blind, Controlled Study to Evaluate the Efficacy and Safety of a Single Injection of Rexlemestrocel-L Combined With HA in Subjects With Moderate to Severe Chronic Low Back Pain

The primary purpose of this study is to evaluate the efficacy of rexlemestrocel-L+HA compared to control in reducing low back pain at 12 months post-treatment and safety of a single injection of rexlemestrocel-L+HA injected into a lumbar intervertebral disc compared to control through 12 months post-treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Degenerative Disc Disease
• Intervention / Treatment: Drug: Rexlemestrocel-L + HA mixture; Drug: Saline

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: David Nunez; Phone Number: 512-826-8897; Email: clinical@mesoblast.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants with moderate to severe low back pain for a duration of at least six months who have failed at least 3 months of conservative care.
• Participants who have moderate radiographic degeneration of an intervertebral disc from L1 to S1, with a single disc suspected of causing chronic lower back pain (CLBP).

Exclusion Criteria:

• Participants who 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.
• Participants with low back pain duration of less than 6 months or greater than 60 months.
• Participants who have not received at least 3 months of conservative treatment for back pain without adequate pain relief.
• Participants taking systemic immunosuppressants.
• Participants with osteoporosis.
• Participants with alcohol or substance abuse problems.
• Participants with severe depression or anxiety.
• Participants with cauda equina syndrome; fibromyalgia, symptomatic central vertebral canal stenosis, lumbar spondylitis or other undifferentiated spondyloarthropathy affecting the index disc.
• Participants having undergone a surgical procedure affecting the structure/biomechanics of the disc (e.g., discectomy, intradiscal electrothermal therapy, intradiscal radiofrequency, artificial disc replacement, interbody fusion, laminectomy, etc.) at the index or adjacent levels.
• Participants who have received any lumbar intradiscal injection into the index disc or adjacent discs within three months prior to the start of screening, other than injection of contrast medium for discography.
• Participants who received an epidural steroid injection within 6 weeks prior to informed consent.
• Participants with evidence of neurologic deficit on any component of the lumbar neurological exam at baseline.
• Participants with sacroiliac (SI) joint pain, as determined by a targeted physical exam, or SI joint injection.
• Participants with facet joint pain, as determined by a medial branch block.
• Participants with more than a single painful level.
• Participants with a full thickness annular tear observed on magnetic resonance imaging (MRI) or discography.
• Participants with low back pain that is less than moderate in severity.
• Participants with extreme low back pain.
• Participants who lack moderate to extreme functional limitations/disability.

Note: Other exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rexlemestrocel-L + HA; Participants will receive 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.	Drug: Rexlemestrocel-L + HA mixture; Rexlemestrocel-L will be combined in 1:1 by-volume ratio with HA solution and the resulting mixture will be administered as intradiscal injection.
Sham Comparator: Control Group; Participants will receive saline solution as a sham procedure to simulate the active treatment injection on Day 0.	Drug: Saline; Saline solution injection adjacent to the index disc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Daily Average Low Back Pain at 12 Months Post-treatment Based on Visual Analog Scale (VAS) Score	Low back pain intensity will be measured using a VAS ranging from 0-100 millimeter (mm). A score of 0 represents no pain and 100 represents worst possible pain.	Baseline and Month 12
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)		Up to Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of 30% VAS Pain Responders at 12 Months Post-treatment	Responders are defined as participants who have at least a 30% decrease from baseline in daily average low back pain VAS score (measured as the average VAS score over 7 days). VAS score ranges from 0 (no pain) to 100 (worst possible pain).	Month 12
Mean Change From Baseline in Quality of Life Measured by Euroqol-5D (EQ-5D) Index Score at 12 Months Post-treatment	The EQ-5D is a generic instrument that consists of 5 dimensions: Mobility, selfcare, usual activities, pain/discomfort, and anxiety/depression, rated over five levels of severity ranging from no issues to extreme issues and the responses can be converted into a single number called an index score. The index scores are calculated ranging from 0 (worst quality of life) to 1 (perfect quality of life).	Baseline and Month 12
Percentage of Minimal Pain Responders at 12 Months Post-treatment	Minimal pain responders are defined as participants who have a low back pain daily average VAS score (measured as the average VAS score over 7 days) of 20 mm or less. VAS score ranges from 0 (no pain) to 100 (worst possible pain).	Month 12
Mean Change From Baseline in Function as Measured by Oswestry Disability Index (ODI) Questionnaire Score at 12 Months Post-treatment	ODI scores ten aspects of the participant's home and work life and analgesic use in a range of 0 (least amount of disability) to 5 (severe disability). The disability index is then calculated by summing the scores for all questions answered, then multiplied by two and reported in a 0 to 100% range where higher numbers indicate a higher level of disability.	Baseline and Month 12
Percentage of Participants With 30% VAS and 10-point ODI Treatment Success at 12 Months Post-treatment	Treatment success based on the percentage of participants who have at least a 30% reduction from baseline in daily average low back pain VAS score (measured as the average VAS score over 7 days) with at least a 10-point decrease from baseline ODI score will be reported.	Month 12
Percentage of Participants Who Ceased Opioid Usage at 24 Months Post-treatment		Month 24

Collaborators and Investigators

• Sponsor: Mesoblast, Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: March 15, 2024
• First Submitted That Met QC Criteria: March 15, 2024
• First Posted (Actual): March 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Spinal Diseases; Bone Diseases; Back Pain; Low Back Pain; Intervertebral Disc Degeneration
• Other Study ID Numbers: MSB-DR004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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