Placebo-controlled Study to Evaluate Rexlemestrocel-L Alone or Combined With Hyaluronic Acid in Participants With Chronic Low Back Pain (MSB-DR003)

Mesoblast

Status and phase: Completed; Phase 3

Conditions: Degenerative Disc Disease

Treatments: Drug: Rexlemestrocel-L; Drug: Placebo; Drug: Rexlemestrocel-L + HA Mixture

Study type: Interventional

Funder types: Industry

Identifiers

NCT02412735

MSB-DR003

Details and patient eligibility

About

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.

Enrollment: 404 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

404 participants in 3 patient groups, including a placebo group

Rexlemestrocel-L

Experimental group

Description:

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).

Treatment:

Drug: Rexlemestrocel-L

Rexlemestrocel-L + HA

Experimental group

Description:

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).

Treatment:

Drug: Rexlemestrocel-L + HA Mixture

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo