Clinical trial NCT02412735: Placebo-controlled Study to Evaluate Rexlemestrocel-L Alone or Combined With Hyaluronic Acid in Participants With Chronic Low Back Pain
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: Mesoblast, Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
First posted: 2015-04-09
Enrollment: 404
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Overall Treatment Success: Bayesian Estimated Response Rate
timeFrame: Up to 24 months
Secondary outcomes:
measure: Effectiveness Based on Pain Responders: Bayesian Estimated Response Rate
timeFrame: Up to 24 months
measure: Effectiveness Based on Functional Responders: Bayesian Estimated Response Rate
timeFrame: Up to 24 months
measure: Effectiveness Based on Treatment Success at 24 Months: Bayesian Estimated Response Rate
timeFrame: Month 24
measure: Effectiveness Based on Minimal Pain Responders at 24 Months: Bayesian Estimated Response Rate
timeFrame: Month 24
measure: Effectiveness Based on Time to First Intervention Over 24 Months
timeFrame: Up to Month 24
measure: Effectiveness Based on Minimal Disability Responders at 24 Months: Bayesian Estimated Response Rate
timeFrame: Month 24
Other outcomes:
measure: Mean Change From Baseline in Low Back Pain Visual Analog Scale (VAS) Score at 1, 3, 6, 12, 18, 24, and 36 Months
timeFrame: Months 1, 3, 6, 12, 18, 24, and 36
Locations:
city: Birmingham
country: United States
facility: Alabama Clinical Therapeutics, LLC
state: Alabama
city: Huntsville
country: United States
facility: Tennessee Valley Pain Consultants
state: Alabama
city: Scottsdale
country: United States
facility: Arizona Pain Specialists
state: Arizona
city: Tempe
country: United States
facility: Physicians Research Group
state: Arizona
city: El Cajon
country: United States
facility: TriWest Research Associates, LLC
state: California
city: Long Beach
country: United States
facility: Memorial Orthopaedics Surgical Group
state: California
city: Newport Beach
country: United States
facility: Newport Beach Headache and Pain
state: California
city: Pasadena
country: United States
facility: Institute for Regenerative Medicine and Clinical Research
state: California
city: Sacramento
country: United States
facility: UC Davis Spine Center
state: California
city: Santa Monica
country: United States
facility: Orthopedic Pain Specialists
state: California
city: Santa Monica
country: United States
facility: The Spine Institute
state: California
city: Santa Rosa
country: United States
facility: Summit Pain Alliance
state: California
city: Walnut Creek
country: United States
facility: Integrated Pain Management
state: California
city: Greenwood Village
country: United States
facility: Denver Back Pain Specialists, LLC
state: Colorado
city: Washington
country: United States
facility: George Washington University Medical Center
state: District of Columbia
city: Fernandina Beach
country: United States
facility: Coastal Clinical Research Specialists
state: Florida
city: Fort Lauderdale
country: United States
facility: Shrock Orthopedic Research, LLC
state: Florida
city: Oakland Park
country: United States
facility: Holy Cross Orthopedics Institute
state: Florida
city: Atlanta
country: United States
facility: Emory Orthopaedics & Spine Center
state: Georgia
city: Marietta
country: United States
facility: Georgia Institute for Clinical Research, LLC
state: Georgia
city: Boise
country: United States
facility: Injury Care Medical Center
state: Idaho
city: Bloomington
country: United States
facility: Millennium Pain Center
state: Illinois
city: Edgewood
country: United States
facility: Otrimed Clinical Research
state: Kentucky
city: Shreveport
country: United States
facility: Orthopedic Specialists of Louisiana
state: Louisiana
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Shakopee
country: United States
facility: MAPS Applied Research Center
state: Minnesota
city: Las Vegas
country: United States
facility: Innovative Pain Care Center
state: Nevada
city: Somerset
country: United States
facility: University Clinical Research
state: New Jersey
city: New York
country: United States
facility: Ainsworth Institute of Pain Management
state: New York
city: Rochester
country: United States
facility: Rochester Regional Health
state: New York
city: Charlotte
country: United States
facility: Carolina Neurosurgery and Spine Associates
state: North Carolina
city: Morrisville
country: United States
facility: On Site Clinical Solutions, LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: The Center for Clinical Research/ Carolinas Pain Institute
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Dayton
country: United States
facility: DOC Clinical Research
state: Ohio
city: Edmond
country: United States
facility: Clinical Investigations, LLC
state: Oklahoma
city: York
country: United States
facility: Orthopaedic and Spine Specialists
state: Pennsylvania
city: Providence
country: United States
facility: RI Hospital-Comprehensive Spine Center
state: Rhode Island
city: Charleston
country: United States
facility: Clinical Trials of South Carolina
state: South Carolina
city: Charleston
country: United States
facility: Greenville Pharmaceutical Research, Inc.
state: South Carolina
city: Plano
country: United States
facility: Texas Back Institute
state: Texas
city: Southlake
country: United States
facility: Spine Team Texas
state: Texas
city: Tyler
country: United States
facility: Precision Spine Care
state: Texas
city: Bountiful
country: United States
facility: Ericksen Research & Development, LLC
state: Utah
city: Draper
country: United States
facility: the SMART Clinic
state: Utah
city: Saint George
country: United States
facility: Hope Research Institute
state: Utah
city: Richmond
country: United States
facility: Virginia iSpine Physicians, PC
state: Virginia
city: Clayton
country: Australia
facility: Monash Medical Center
state: Victoria
Study officials:
affiliation: Mesoblast, Ltd.
name: Roger Brown
role: STUDY_DIRECTOR
References: