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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02412735




Registration number
NCT02412735
Ethics application status
Date submitted
25/03/2015
Date registered
9/04/2015
Date last updated
2/06/2020

Titles & IDs
Public title
Placebo-controlled Study to Evaluate Rexlemestrocel-L Alone or Combined With Hyaluronic Acid in Subjects With Chronic Low Back Pain
Scientific 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
Secondary ID [1] 0 0
MSB-DR003
Universal Trial Number (UTN)
Trial acronym
MSB-DR003
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Degenerative Disc Disease 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - rexlemestrocel-L
Treatment: Drugs - rexlemestrocel-L + HA
Treatment: Drugs - Placebo

Experimental: rexlemestrocel-L - rexlemestrocel-L alone": 2.0 mL formulation of approximately 6 million rexlemestrocel-L cells

Experimental: rexlemestrocel-L + HA - rexlemestrocel-L + HA": 2.0mL 6 million rexlemestrocel-L cells

Placebo Comparator: Placebo - saline control: 2.0 mL saline solution


Treatment: Drugs: rexlemestrocel-L
rexlemestrocel-L alone": 2.0 mL formulation of approximately 6 million rexlemestrocel-L cells - Intervention will be injected into the painful intervertebral disc

Treatment: Drugs: rexlemestrocel-L + HA
rexlemestrocel-L + HA": 2.0mL 6 million rexlemestrocel-L cells with 1% HA - Intervention will be injected into the painful intervertebral disc

Treatment: Drugs: Placebo
saline control: 2.0 mL saline solution

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Treatment Success (composite responder analysis of low back pain Visual Analogue Scale (VAS) score, Oswestry Disability Index (ODI) score and no post-treatment interventions) - • To determine Overall Treatment Success of rexlemestrocel-L alone or rexlemestrocel-L+HA through 24 months based on a composite responder analysis
Timepoint [1] 0 0
24 Months
Secondary outcome [1] 0 0
Effectiveness (Pain Responder analysis) - • To evaluate the effectiveness of rexlemestrocel-L alone or rexlemestrocel-L+HA in reducing chronic low back pain by performing a Pain Responder analysis through 24 months post-treatment
Timepoint [1] 0 0
24 months
Secondary outcome [2] 0 0
Effectiveness (Functional Responder analysis) - • To evaluate the effectiveness of rexlemestrocel-L alone or rexlemestrocel-L+HA in improving function by performing a Functional Responder analysis through 24 months post-treatment
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
Effectiveness (Treatment Success at 24 months) - To determine the Treatment Success at 24 months of rexlemestrocel-L alone or rexlemestrocel-L+HA based upon a composite responder analysis
Timepoint [3] 0 0
24 months
Secondary outcome [4] 0 0
Effectiveness (Minimal Pain Responder at 24 months) - Minimal Pain Responder at 24 Months: Measured as subjects meeting low back pain VAS score threshold
Timepoint [4] 0 0
24 months
Secondary outcome [5] 0 0
Effectiveness (Time to first intervention) - To evaluate the effectiveness of rexlemestrocel-L alone or rexlemestrocel-L+HA on reducing the time to additional interventions at the treated level over 24 months post-treatment.
Timepoint [5] 0 0
24 months

Eligibility
Key inclusion criteria
- Male and female subjects 18 years of age and older

- If female of childbearing potential, subject 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 subject 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 CLBP Chronic low back pain
associated with moderate radiographic degeneration at a lumbar disc is defined as the
following (subject 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. 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 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 VAS
(average pain over 24 hours)

f. Leg pain =20mm in both legs on a 100mm VAS scale

g. ODI score of at least 30 and no more than 90 on a 100 point scale.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Female subjects who are pregnant or nursing, or women planning to become pregnant in
the first 24 months post-treatment

- Extreme obesity, as defined by 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 subject.

- 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 immunosuppresants

- 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.

- Subjects 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Monash Medical Center - Clayton
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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Arizona
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California
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Colorado
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District of Columbia
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Florida
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Georgia
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Idaho
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Illinois
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United States of America
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Kentucky
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Louisiana
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Minnesota
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Nevada
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New Jersey
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New York
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North Carolina
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Ohio
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Oklahoma
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Pennsylvania
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Rhode Island
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South Carolina
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Texas
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Utah
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United States of America
State/province [24] 0 0
Virginia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Mesoblast, Ltd.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Quintiles, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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 subjects with chronic low back pain (> 6 months)
associated with moderate radiographic degenerative changes of a disc
Trial website
https://clinicaltrials.gov/show/NCT02412735
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Roger Brown
Address 0 0
Mesoblast, Ltd.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications