Placebo-controlled Study to Evaluate Rexlemestrocel-L Alone or Combined With Hyaluronic Acid in Participants With Chronic Low Back Pain
Condition: Degenerative Disc Disease
MeSH terms: Intervertebral Disc Degeneration; Back Pain; Low Back Pain
Intervention: Rexlemestrocel-L; Rexlemestrocel-L + HA Mixture; Placebo
Intervention description: Rexlemestrocel-L injection; Rexlemestrocel-L was combined in 1:1 by-volume ratio with HA solution and the resulting mixture was injected; Saline control solution
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 404.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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

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.
    

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.