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

• Sponsor: Mesoblast, Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02412735
• Collaborator: Quintiles, Inc. (Industry)
• Enrollment: 404
• Locations: 48
• Arms: 3
• Actual Duration (Months): 75.3
• Patients Per Site: 8.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Degenerative Disc Disease	Drug: Rexlemestrocel-L; Drug: Rexlemestrocel-L + HA Mixture; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 404 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Mar 6, 2015
• Actual Primary Completion Date: May 15, 2020
• Actual Study Completion Date: Jun 15, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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).	Drug: Rexlemestrocel-L; Rexlemestrocel-L injection
Experimental: 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).	Drug: Rexlemestrocel-L + HA Mixture; Rexlemestrocel-L was combined in 1:1 by-volume ratio with HA solution and the resulting mixture was injected
Placebo Comparator: Placebo Participants received saline solution as matching-placebo on Day 0 (Visit 2).	Drug: Placebo; Saline control solution

Outcome Measures

Primary Outcome Measures

1. Overall Treatment Success: Bayesian Estimated Response Rate [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 was based upon the average of multiple Bayesian simulations.

Secondary Outcome Measures

1. Effectiveness Based on Number of Pain Responders [Up to 24 months]

   A participant was defined as a pain responder for a given study visit if they achieved at least a 50% reduction from Baseline in the lower-back pain VAS score (average pain over 24 hours), as reported during in-clinic assessment. The participant should be qualified as a pain responder at both 12 and 24 months post-treatment, and must not have received a post-treatment intervention through 24 months' follow-up. Any participant that did not have a minimum of a visit at 3 months (Study Visit 4) was considered a non-responder for this outcome measure.

2. Effectiveness Based on Number of Functional Responders [Up to 24 months]

   A participant was defined as a functional responder for a given study visit if they achieved at least a 15-point reduction from Baseline in ODI score, as reported during in-clinic assessment. The participant should be qualified as a functional responder at both 12 and 24 months post-treatment, and must not have received a post-treatment intervention through 24 months' follow-up; any participant that did not have a minimum of a visit at 3 months (Study Visit 4) was considered a non-responder for this outcome measure.

3. Effectiveness Based on Treatment Success at 24 Months Reported as Number of Responders [Month 24]

   A treatment responder with treatment success was defined as a participant who met the 3 conditions of a composite responder analysis as: 50% or greater reduction in the lower-back pain VAS score; 15-point or greater reduction in ODI score; and lack of post-treatment interventions at the treated level as of the study visit. The participants qualified as responders if they satisfied the above conditions at the 24-month follow-up visit alone. Any participant that did not have a minimum of a visit at 3 months (Study Visit 4) was considered a non-responder for this outcome measure.

4. Effectiveness Based on Number of Minimal Pain Responders at 24 Months [Month 24]

   A minimal pain responder was defined as a participant who achieved a lower-back pain VAS score (average pain over 24 hours) of 20 mm or less at the given study visit. The participants qualified as responders if they satisfied the above condition at 24 months post-treatment, and did not receive a post-treatment intervention through 24 months' follow-up. Any participant that did not have a minimum of a visit at 3 months (Study Visit 4) was considered a non-responder for this outcome measure.

5. Effectiveness Based on Time to First Intervention Over 24 Months [Month 24]

   The effectiveness of the study drug was evaluated based on its ability in increasing the time to additional interventions at the treated level over 24 months post-treatment.

6. Effectiveness Based on Number of Minimal Disability Responders at 24 Months [Month 24]

   A minimal pain responder was defined as a participant who achieved an ODI score of 20% or less at the given study visit. The participants qualified as responders if they satisfied the above condition at 24 months post-treatment, and did not receive a post-treatment intervention through 24 months' follow-up. Any participant that did not have a minimum of a visit at 3 months (Study Visit 4) was considered a non-responder for this outcome measure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

1. 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)

2. Leg pain ≤20mm in both legs on a 100mm VAS scale

3. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Clinical Therapeutics, LLC	Birmingham	Alabama	United States	35235
2	Tennessee Valley Pain Consultants	Huntsville	Alabama	United States	35801
3	Arizona Pain Specialists	Scottsdale	Arizona	United States	85258
4	Physicians Research Group	Tempe	Arizona	United States	85284-2604
5	TriWest Research Associates, LLC	El Cajon	California	United States	92020-4124
6	Memorial Orthopaedics Surgical Group	Long Beach	California	United States	90806
7	Newport Beach Headache and Pain	Newport Beach	California	United States	92660
8	Institute for Regenerative Medicine and Clinical Research	Pasadena	California	United States	91105
9	UC Davis Spine Center	Sacramento	California	United States	95816
10	Orthopedic Pain Specialists	Santa Monica	California	United States	90403
11	The Spine Institute	Santa Monica	California	United States	90403
12	Summit Pain Alliance	Santa Rosa	California	United States	95401
13	Integrated Pain Management	Walnut Creek	California	United States	94598
14	Denver Back Pain Specialists, LLC	Greenwood Village	Colorado	United States	80111
15	George Washington University Medical Center	Washington	District of Columbia	United States	20037
16	Coastal Clinical Research Specialists	Fernandina Beach	Florida	United States	32034
17	Shrock Orthopedic Research, LLC	Fort Lauderdale	Florida	United States	33316
18	Holy Cross Orthopedics Institute	Oakland Park	Florida	United States	33334
19	Emory Orthopaedics & Spine Center	Atlanta	Georgia	United States	30329
20	Georgia Institute for Clinical Research, LLC	Marietta	Georgia	United States	30060
21	Injury Care Medical Center	Boise	Idaho	United States	83713
22	Millennium Pain Center	Bloomington	Illinois	United States	61701
23	Otrimed Clinical Research	Edgewood	Kentucky	United States	41017
24	Orthopedic Specialists of Louisiana	Shreveport	Louisiana	United States	71103
25	Mayo Clinic	Rochester	Minnesota	United States	55905
26	MAPS Applied Research Center	Shakopee	Minnesota	United States	55379
27	Innovative Pain Care Center	Las Vegas	Nevada	United States	89129
28	University Clinical Research	Somerset	New Jersey	United States	08873
29	Ainsworth Institute of Pain Management	New York	New York	United States	10022
30	Rochester Regional Health	Rochester	New York	United States	14626
31	Carolina Neurosurgery and Spine Associates	Charlotte	North Carolina	United States	28204
32	On Site Clinical Solutions, LLC	Morrisville	North Carolina	United States	28117
33	The Center for Clinical Research/ Carolinas Pain Institute	Winston-Salem	North Carolina	United States	27103
34	Cleveland Clinic	Cleveland	Ohio	United States	44106
35	DOC Clinical Research	Dayton	Ohio	United States	45432
36	Clinical Investigations, LLC	Edmond	Oklahoma	United States	73013
37	Orthopaedic and Spine Specialists	York	Pennsylvania	United States	17402
38	RI Hospital-Comprehensive Spine Center	Providence	Rhode Island	United States	02903
39	Clinical Trials of South Carolina	Charleston	South Carolina	United States	29406
40	Greenville Pharmaceutical Research, Inc.	Charleston	South Carolina	United States	29406
41	Texas Back Institute	Plano	Texas	United States	75093
42	Spine Team Texas	Southlake	Texas	United States	76092
43	Precision Spine Care	Tyler	Texas	United States	75701
44	Ericksen Research & Development, LLC	Bountiful	Utah	United States	84010
45	the SMART Clinic	Draper	Utah	United States	84020
46	Hope Research Institute	Saint George	Utah	United States	84790
47	Virginia iSpine Physicians, PC	Richmond	Virginia	United States	23235
48	Monash Medical Center	Clayton	Victoria	Australia	3168

Sponsors and Collaborators

• Mesoblast, Ltd.
• Quintiles, Inc.

Investigators

• Study Director: Roger Brown, Mesoblast, Ltd.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 17, 2018

More Information

Publications

None provided.

• Responsible Party: Mesoblast, Ltd.
• ClinicalTrials.gov Identifier: NCT02412735
• Other Study ID Numbers: MSB-DR003
• First Posted: Apr 9, 2015
• Last Update Posted: Jan 20, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Mesoblast, Ltd.: 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
• Additional relevant MeSH terms: Intervertebral Disc Degeneration; Back Pain; Low Back Pain

Study Results

Participant Flow

Recruitment Details	Starting on March 6, 2015, a total of 404 participants were enrolled at investigative sites in Australia and the United States. Data is reported for the primary outcome measure and for adverse events reported up to the data cutoff date for the primary analysis, May 15, 2020.

Arm/Group Title	Rexlemestrocel-L	Rexlemestrocel-L + HA	Placebo
Arm/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).	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).	Participants received saline solution as matching-placebo on Day 0 (Visit 2).
Period Title: Overall Study
STARTED	143	129	132
Received Treatment	140	128	130
COMPLETED	97	85	86
NOT COMPLETED	46	44	46

Baseline Characteristics

Arm/Group Title	Rexlemestrocel-L	Rexlemestrocel-L + HA	Placebo	Total
Arm/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).	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 HA solution on Day 0 (Visit 2).	Participants received saline solution as matching-placebo on Day 0 (Visit 2).	Total of all reporting groups
Overall Participants	143	129	132	404
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.1 (10.81)	42.9 (11.66)	43.3 (10.45)	42.8 (10.96)
Sex: Female, Male (Count of Participants)
Female	60 42%	54 41.9%	61 46.2%	175 43.3%
Male	83 58%	75 58.1%	71 53.8%	229 56.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 6.3%	4 3.1%	11 8.3%	24 5.9%
Not Hispanic or Latino	133 93%	121 93.8%	119 90.2%	373 92.3%
Unknown or Not Reported	1 0.7%	4 3.1%	2 1.5%	7 1.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 0.8%	1 0.2%
Asian	0 0%	4 3.1%	3 2.3%	7 1.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	6 4.2%	6 4.7%	6 4.5%	18 4.5%
White	133 93%	118 91.5%	118 89.4%	369 91.3%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	4 2.8%	1 0.8%	4 3%	9 2.2%

Outcome Measures

1. Primary Outcome

Title	Overall Treatment Success: Bayesian Estimated Response Rate
Description	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 was based upon the average of multiple Bayesian simulations.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

The ITT Analysis Set included all participants who were randomized, regardless of whether or not the participant was treated, or post-treatment measures were performed.

Arm/Group Title	Rexlemestrocel-L	Rexlemestrocel-L + HA	Placebo
Arm/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).	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 HA solution on Day 0 (Visit 2).	Participants received saline solution as matching-placebo on Day 0 (Visit 2).
Measure Participants	143	129	132
Mean (Standard Deviation) [rate]	0.267 (0.038)	0.335 (0.043)	0.313 (0.041)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rexlemestrocel-L, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	The superiority threshold was 0.9875.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		The posterior probability of superiority to placebo was 0.2072.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Rexlemestrocel-L + HA, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	The superiority threshold was 0.9875.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		The posterior probability of superiority to placebo was 0.6427.

2. Secondary Outcome

Title	Effectiveness Based on Number of Pain Responders
Description	A participant was defined as a pain responder for a given study visit if they achieved at least a 50% reduction from Baseline in the lower-back pain VAS score (average pain over 24 hours), as reported during in-clinic assessment. The participant should be qualified as a pain responder at both 12 and 24 months post-treatment, and must not have received a post-treatment intervention through 24 months' follow-up. Any participant that did not have a minimum of a visit at 3 months (Study Visit 4) was considered a non-responder for this outcome measure.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Effectiveness Based on Number of Functional Responders
Description	A participant was defined as a functional responder for a given study visit if they achieved at least a 15-point reduction from Baseline in ODI score, as reported during in-clinic assessment. The participant should be qualified as a functional responder at both 12 and 24 months post-treatment, and must not have received a post-treatment intervention through 24 months' follow-up; any participant that did not have a minimum of a visit at 3 months (Study Visit 4) was considered a non-responder for this outcome measure.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Effectiveness Based on Treatment Success at 24 Months Reported as Number of Responders
Description	A treatment responder with treatment success was defined as a participant who met the 3 conditions of a composite responder analysis as: 50% or greater reduction in the lower-back pain VAS score; 15-point or greater reduction in ODI score; and lack of post-treatment interventions at the treated level as of the study visit. The participants qualified as responders if they satisfied the above conditions at the 24-month follow-up visit alone. Any participant that did not have a minimum of a visit at 3 months (Study Visit 4) was considered a non-responder for this outcome measure.
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Effectiveness Based on Number of Minimal Pain Responders at 24 Months
Description	A minimal pain responder was defined as a participant who achieved a lower-back pain VAS score (average pain over 24 hours) of 20 mm or less at the given study visit. The participants qualified as responders if they satisfied the above condition at 24 months post-treatment, and did not receive a post-treatment intervention through 24 months' follow-up. Any participant that did not have a minimum of a visit at 3 months (Study Visit 4) was considered a non-responder for this outcome measure.
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Effectiveness Based on Time to First Intervention Over 24 Months
Description	The effectiveness of the study drug was evaluated based on its ability in increasing the time to additional interventions at the treated level over 24 months post-treatment.
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Effectiveness Based on Number of Minimal Disability Responders at 24 Months
Description	A minimal pain responder was defined as a participant who achieved an ODI score of 20% or less at the given study visit. The participants qualified as responders if they satisfied the above condition at 24 months post-treatment, and did not receive a post-treatment intervention through 24 months' follow-up. Any participant that did not have a minimum of a visit at 3 months (Study Visit 4) was considered a non-responder for this outcome measure.
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Up to approximately 3 years
Adverse Event Reporting Description	All-cause Mortality: The ITT Analysis Set included all participants who were randomized, regardless of whether or not the participant was treated, or post-treatment measures were performed. Serious and Other Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Arm/Group Title	Rexlemestrocel-L		Rexlemestrocel-L + HA		Placebo
Arm/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).		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).		Participants received saline solution as matching-placebo on Day 0 (Visit 2).
All Cause Mortality
	Rexlemestrocel-L		Rexlemestrocel-L + HA		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/143 (0%)		0/129 (0%)		0/132 (0%)
Serious Adverse Events
	Rexlemestrocel-L		Rexlemestrocel-L + HA		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/140 (9.3%)		12/128 (9.4%)		7/130 (5.4%)
Cardiac disorders
Acute myocardial infarction	0/140 (0%)		1/128 (0.8%)		0/130 (0%)
Angina pectoris	1/140 (0.7%)		0/128 (0%)		0/130 (0%)
Coronary artery disease	0/140 (0%)		1/128 (0.8%)		0/130 (0%)
Myocardial infarction	0/140 (0%)		1/128 (0.8%)		0/130 (0%)
Gastrointestinal disorders
Small intestinal obstruction	1/140 (0.7%)		0/128 (0%)		0/130 (0%)
Hepatobiliary disorders
Biliary dyskinesia	1/140 (0.7%)		0/128 (0%)		0/130 (0%)
Hepatic haematoma	0/140 (0%)		0/128 (0%)		1/130 (0.8%)
Infections and infestations
Appendicitis	2/140 (1.4%)		1/128 (0.8%)		1/130 (0.8%)
Diverticulitis	1/140 (0.7%)		1/128 (0.8%)		0/130 (0%)
Escherichia bacteraemia	0/140 (0%)		0/128 (0%)		1/130 (0.8%)
Pneumonia	0/140 (0%)		1/128 (0.8%)		0/130 (0%)
Pyelonephritis acute	0/140 (0%)		0/128 (0%)		1/130 (0.8%)
Injury, poisoning and procedural complications
Cartilage injury	1/140 (0.7%)		0/128 (0%)		0/130 (0%)
Fall	0/140 (0%)		0/128 (0%)		1/130 (0.8%)
Femur fracture	1/140 (0.7%)		0/128 (0%)		0/130 (0%)
Patella fracture	0/140 (0%)		1/128 (0.8%)		0/130 (0%)
Road traffic accident	1/140 (0.7%)		0/128 (0%)		0/130 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/140 (0%)		0/128 (0%)		3/130 (2.3%)
Arthralgia	0/140 (0%)		1/128 (0.8%)		0/130 (0%)
Intervertebral disc degeneration	1/140 (0.7%)		0/128 (0%)		0/130 (0%)
Osteoarthritis	1/140 (0.7%)		0/128 (0%)		0/130 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma	1/140 (0.7%)		0/128 (0%)		0/130 (0%)
Nervous system disorders
Migraine	0/140 (0%)		1/128 (0.8%)		0/130 (0%)
Neuralgia	0/140 (0%)		0/128 (0%)		1/130 (0.8%)
Perineurial cyst	1/140 (0.7%)		0/128 (0%)		0/130 (0%)
Radiculopathy	1/140 (0.7%)		0/128 (0%)		0/130 (0%)
Sacral radiculopathy	1/140 (0.7%)		0/128 (0%)		0/130 (0%)
Seizure	0/140 (0%)		1/128 (0.8%)		0/130 (0%)
Spinal meningeal cyst	1/140 (0.7%)		0/128 (0%)		0/130 (0%)
Product Issues
Device breakage	1/140 (0.7%)		0/128 (0%)		0/130 (0%)
Psychiatric disorders
Suicidal ideation	0/140 (0%)		1/128 (0.8%)		0/130 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax spontaneous	0/140 (0%)		1/128 (0.8%)		0/130 (0%)
Other (Not Including Serious) Adverse Events
	Rexlemestrocel-L		Rexlemestrocel-L + HA		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	107/140 (76.4%)		98/128 (76.6%)		98/130 (75.4%)
Musculoskeletal and connective tissue disorders
Back pain	49/140 (35%)		54/128 (42.2%)		46/130 (35.4%)
Pain in extremity	17/140 (12.1%)		17/128 (13.3%)		18/130 (13.8%)
Arthralgia	13/140 (9.3%)		15/128 (11.7%)		12/130 (9.2%)
Muscle spasms	8/140 (5.7%)		7/128 (5.5%)		10/130 (7.7%)
Neck pain	3/140 (2.1%)		6/128 (4.7%)		10/130 (7.7%)
Nervous system disorders
Hypoesthesia	10/140 (7.1%)		8/128 (6.3%)		11/130 (8.5%)
Paresthesia	11/140 (7.9%)		5/128 (3.9%)		4/130 (3.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Publications (abstracts, posters or presentations) must be presented to the Publication Steering Committee for review prior to submission or public display and are not allowed prior to the publication of the primary manuscript, or eighteen (18) months from the conclusion of the Study. PI shall provide Sponsor a copy of any proposed public disclosure at least 30 days prior to submission. Sponsor may ask PI to delay the disclosure for a maximum of 60 days to file proprietary protection.