A Prospective, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of a Single Injection of Rexlemestrocel-L Alone or Combined With Hyaluronic Acid (HA) in Subjects With Chronic Low Back Pain
Overview
- Phase
- Phase 3
- Intervention
- Rexlemestrocel-L
- Conditions
- Degenerative Disc Disease
- Sponsor
- Mesoblast, Ltd.
- Enrollment
- 404
- Locations
- 48
- Primary Endpoint
- Overall Treatment Success: Bayesian Estimated Response Rate
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
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):
- •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
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:
- •Contrast medium (discography or other diagnostic injection)
- •Nerve-blocking anesthetics (e.g., lidocaine, bupivacaine)
- •Antibiotics
- •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
Arms & Interventions
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).
Intervention: Rexlemestrocel-L
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).
Intervention: Rexlemestrocel-L + HA Mixture
Placebo
Participants received saline solution as matching-placebo on Day 0 (Visit 2).
Intervention: Placebo
Outcomes
Primary Outcomes
Overall Treatment Success: Bayesian Estimated Response Rate
Time Frame: Up to 24 months
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.
Secondary Outcomes
- 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 Pain Responders: Bayesian Estimated Response Rate(Up to 24 months)
- Effectiveness Based on Minimal Disability Responders at 24 Months: Bayesian Estimated Response Rate(Month 24)
- Effectiveness Based on Time to First Intervention Over 24 Months(Up to Month 24)