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

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ClinicalTrials.gov Identifier: NCT02412735
Recruitment Status : Completed
First Posted : April 9, 2015
Results First Posted : January 17, 2022
Last Update Posted : January 17, 2022
Sponsor:
Collaborator:
Quintiles, Inc.
Information provided by (Responsible Party):
Mesoblast, Ltd.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Degenerative Disc Disease
Interventions Drug: Rexlemestrocel-L
Drug: Rexlemestrocel-L + HA Mixture
Drug: Placebo
Enrollment 404
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.
Pre-assignment Details  
Arm/Group Title Rexlemestrocel-L Rexlemestrocel-L + HA Placebo
Hide 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
Reason Not Completed
Adverse Event             0             1             2
Withdrawal by Subject             23             27             22
Investigator Decision             3             3             2
Lost to Follow-up             17             11             18
Reason not Specified             3             2             2
Arm/Group Title Rexlemestrocel-L Rexlemestrocel-L + HA Placebo Total
Hide 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 Number of Baseline Participants 143 129 132 404
Hide Baseline 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.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 143 participants 129 participants 132 participants 404 participants
42.1  (10.81) 42.9  (11.66) 43.3  (10.45) 42.8  (10.96)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 143 participants 129 participants 132 participants 404 participants
Female
60
  42.0%
54
  41.9%
61
  46.2%
175
  43.3%
Male
83
  58.0%
75
  58.1%
71
  53.8%
229
  56.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 143 participants 129 participants 132 participants 404 participants
Hispanic or Latino
9
   6.3%
4
   3.1%
11
   8.3%
24
   5.9%
Not Hispanic or Latino
133
  93.0%
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)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 143 participants 129 participants 132 participants 404 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
1
   0.8%
1
   0.2%
Asian
0
   0.0%
4
   3.1%
3
   2.3%
7
   1.7%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
6
   4.2%
6
   4.7%
6
   4.5%
18
   4.5%
White
133
  93.0%
118
  91.5%
118
  89.4%
369
  91.3%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
4
   2.8%
1
   0.8%
4
   3.0%
9
   2.2%
1.Primary Outcome
Title Overall Treatment Success: Bayesian Estimated Response Rate
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 143 129 132
Mean (Standard Deviation)
Unit of Measure: rate
0.267  (0.038) 0.335  (0.043) 0.313  (0.041)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rexlemestrocel-L, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The superiority threshold was 0.9875.
Other Statistical Analysis The posterior probability of superiority to placebo was 0.2072.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Rexlemestrocel-L + HA, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The superiority threshold was 0.9875.
Other Statistical Analysis The posterior probability of superiority to placebo was 0.6427.
2.Secondary Outcome
Title Effectiveness Based on Number of Pain Responders
Hide 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 Not Reported
3.Secondary Outcome
Title Effectiveness Based on Number of Functional Responders
Hide 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 Not Reported
4.Secondary Outcome
Title Effectiveness Based on Treatment Success at 24 Months Reported as Number of Responders
Hide 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 Not Reported
5.Secondary Outcome
Title Effectiveness Based on Number of Minimal Pain Responders at 24 Months
Hide 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 Not Reported
6.Secondary Outcome
Title Effectiveness Based on Time to First Intervention Over 24 Months
Hide 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 Not Reported
7.Secondary Outcome
Title Effectiveness Based on Number of Minimal Disability Responders at 24 Months
Hide 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 Not Reported
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/143 (0.00%)   0/129 (0.00%)   0/132 (0.00%) 
Hide Serious Adverse Events
Rexlemestrocel-L Rexlemestrocel-L + HA Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/140 (9.29%)   12/128 (9.38%)   7/130 (5.38%) 
Cardiac disorders       
Acute myocardial infarction  1  0/140 (0.00%)  1/128 (0.78%)  0/130 (0.00%) 
Angina pectoris  1  1/140 (0.71%)  0/128 (0.00%)  0/130 (0.00%) 
Coronary artery disease  1  0/140 (0.00%)  1/128 (0.78%)  0/130 (0.00%) 
Myocardial infarction  1  0/140 (0.00%)  1/128 (0.78%)  0/130 (0.00%) 
Gastrointestinal disorders       
Small intestinal obstruction  1  1/140 (0.71%)  0/128 (0.00%)  0/130 (0.00%) 
Hepatobiliary disorders       
Biliary dyskinesia  1  1/140 (0.71%)  0/128 (0.00%)  0/130 (0.00%) 
Hepatic haematoma  1  0/140 (0.00%)  0/128 (0.00%)  1/130 (0.77%) 
Infections and infestations       
Appendicitis  1  2/140 (1.43%)  1/128 (0.78%)  1/130 (0.77%) 
Diverticulitis  1  1/140 (0.71%)  1/128 (0.78%)  0/130 (0.00%) 
Escherichia bacteraemia  1  0/140 (0.00%)  0/128 (0.00%)  1/130 (0.77%) 
Pneumonia  1  0/140 (0.00%)  1/128 (0.78%)  0/130 (0.00%) 
Pyelonephritis acute  1  0/140 (0.00%)  0/128 (0.00%)  1/130 (0.77%) 
Injury, poisoning and procedural complications       
Cartilage injury  1  1/140 (0.71%)  0/128 (0.00%)  0/130 (0.00%) 
Fall  1  0/140 (0.00%)  0/128 (0.00%)  1/130 (0.77%) 
Femur fracture  1  1/140 (0.71%)  0/128 (0.00%)  0/130 (0.00%) 
Patella fracture  1  0/140 (0.00%)  1/128 (0.78%)  0/130 (0.00%) 
Road traffic accident  1  1/140 (0.71%)  0/128 (0.00%)  0/130 (0.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  0/140 (0.00%)  0/128 (0.00%)  3/130 (2.31%) 
Arthralgia  1  0/140 (0.00%)  1/128 (0.78%)  0/130 (0.00%) 
Intervertebral disc degeneration  1  1/140 (0.71%)  0/128 (0.00%)  0/130 (0.00%) 
Osteoarthritis  1  1/140 (0.71%)  0/128 (0.00%)  0/130 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Bladder transitional cell carcinoma  1  1/140 (0.71%)  0/128 (0.00%)  0/130 (0.00%) 
Nervous system disorders       
Migraine  1  0/140 (0.00%)  1/128 (0.78%)  0/130 (0.00%) 
Neuralgia  1  0/140 (0.00%)  0/128 (0.00%)  1/130 (0.77%) 
Perineurial cyst  1  1/140 (0.71%)  0/128 (0.00%)  0/130 (0.00%) 
Radiculopathy  1  1/140 (0.71%)  0/128 (0.00%)  0/130 (0.00%) 
Sacral radiculopathy  1  1/140 (0.71%)  0/128 (0.00%)  0/130 (0.00%) 
Seizure  1  0/140 (0.00%)  1/128 (0.78%)  0/130 (0.00%) 
Spinal meningeal cyst  1  1/140 (0.71%)  0/128 (0.00%)  0/130 (0.00%) 
Product Issues       
Device breakage  1  1/140 (0.71%)  0/128 (0.00%)  0/130 (0.00%) 
Psychiatric disorders       
Suicidal ideation  1  0/140 (0.00%)  1/128 (0.78%)  0/130 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Pneumothorax spontaneous  1  0/140 (0.00%)  1/128 (0.78%)  0/130 (0.00%) 
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rexlemestrocel-L Rexlemestrocel-L + HA Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   107/140 (76.43%)   98/128 (76.56%)   98/130 (75.38%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  49/140 (35.00%)  54/128 (42.19%)  46/130 (35.38%) 
Pain in extremity  1  17/140 (12.14%)  17/128 (13.28%)  18/130 (13.85%) 
Arthralgia  1  13/140 (9.29%)  15/128 (11.72%)  12/130 (9.23%) 
Muscle spasms  1  8/140 (5.71%)  7/128 (5.47%)  10/130 (7.69%) 
Neck pain  1  3/140 (2.14%)  6/128 (4.69%)  10/130 (7.69%) 
Nervous system disorders       
Hypoesthesia  1  10/140 (7.14%)  8/128 (6.25%)  11/130 (8.46%) 
Paresthesia  1  11/140 (7.86%)  5/128 (3.91%)  4/130 (3.08%) 
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Christopher James, VP Head of Clinical Operations
Organization: Mesoblast, Inc.
Phone: 212-880-2060 ext 7925
EMail: Christopher.James@Mesoblast.com
Layout table for additonal information
Responsible Party: Mesoblast, Ltd.
ClinicalTrials.gov Identifier: NCT02412735    
Other Study ID Numbers: MSB-DR003
First Submitted: March 25, 2015
First Posted: April 9, 2015
Results First Submitted: December 17, 2021
Results First Posted: January 17, 2022
Last Update Posted: January 17, 2022