Trial Outcomes & Findings for Placebo-controlled Study to Evaluate Rexlemestrocel-L Alone or Combined With Hyaluronic Acid in Participants With Chronic Low Back Pain (NCT NCT02412735)

NCT ID: NCT02412735

Last Updated: 2022-10-19

Results Overview

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 (proportion of participants with response presented as Bayesian estimate\[BE\]) was based upon the average of multiple Bayesian simulations.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 404 participants
• Primary outcome timeframe: Up to 24 months
• Results posted on: 2022-10-19

Participant Flow

Starting on March 6, 2015, a total of 404 participants were enrolled at investigative sites in Australia and the United States.

Participant milestones

Measure	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).	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).	Placebo Participants received saline solution as matching-placebo on Day 0 (Visit 2).
Overall Study STARTED	143	129	132
Overall Study Received Treatment	140	128	130
Overall Study COMPLETED	97	85	86
Overall Study NOT COMPLETED	46	44	46

Reasons for withdrawal

Measure	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).	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).	Placebo Participants received saline solution as matching-placebo on Day 0 (Visit 2).
Overall Study Adverse Event	0	1	2
Overall Study Withdrawal by Subject	23	27	22
Overall Study Investigator Decision	3	3	2
Overall Study Lost to Follow-up	17	11	18
Overall Study Reason not Specified	3	2	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Rexlemestrocel-L n=143 Participants 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).	Rexlemestrocel-L + HA n=129 Participants 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).	Placebo n=132 Participants Participants received saline solution as matching-placebo on Day 0 (Visit 2).	Total n=404 Participants Total of all reporting groups
Age, Continuous	42.1 years STANDARD_DEVIATION 10.81 • n=5 Participants	42.9 years STANDARD_DEVIATION 11.66 • n=7 Participants	43.3 years STANDARD_DEVIATION 10.45 • n=5 Participants	42.8 years STANDARD_DEVIATION 10.96 • n=4 Participants
Sex: Female, Male Female	60 Participants n=5 Participants	54 Participants n=7 Participants	61 Participants n=5 Participants	175 Participants n=4 Participants
Sex: Female, Male Male	83 Participants n=5 Participants	75 Participants n=7 Participants	71 Participants n=5 Participants	229 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	4 Participants n=7 Participants	11 Participants n=5 Participants	24 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	133 Participants n=5 Participants	121 Participants n=7 Participants	119 Participants n=5 Participants	373 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants
Race (NIH/OMB) White	133 Participants n=5 Participants	118 Participants n=7 Participants	118 Participants n=5 Participants	369 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 24 months

Population: 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.

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 (proportion of participants with response presented as Bayesian estimate[BE]) was based upon the average of multiple Bayesian simulations.

Outcome measures

Measure	Rexlemestrocel-L n=143 Participants 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).	Rexlemestrocel-L + HA n=129 Participants 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).	Placebo n=132 Participants Participants received saline solution as matching-placebo on Day 0 (Visit 2).
Overall Treatment Success: Bayesian Estimated Response Rate	0.267 BE proportion of participants Standard Deviation 0.038	0.335 BE proportion of participants Standard Deviation 0.043	0.313 BE proportion of participants Standard Deviation 0.041

SECONDARY outcome

Timeframe: Up to 24 months

Population: 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.

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. The average response rate (proportion of participants with response presented as BE) was based upon the average of multiple Bayesian simulations.

Outcome measures

Measure	Rexlemestrocel-L n=143 Participants 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).	Rexlemestrocel-L + HA n=129 Participants 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).	Placebo n=132 Participants Participants received saline solution as matching-placebo on Day 0 (Visit 2).
Effectiveness Based on Pain Responders: Bayesian Estimated Response Rate	0.352 BE proportion of participants Standard Deviation 0.041	0.472 BE proportion of participants Standard Deviation 0.045	0.388 BE proportion of participants Standard Deviation 0.044

SECONDARY outcome

Timeframe: Up to 24 months

Population: 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.

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. The average response rate (proportion of participants with response presented as BE) was based upon the average of multiple Bayesian simulations.

Outcome measures

Measure	Rexlemestrocel-L n=143 Participants 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).	Rexlemestrocel-L + HA n=129 Participants 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).	Placebo n=132 Participants Participants received saline solution as matching-placebo on Day 0 (Visit 2).
Effectiveness Based on Functional Responders: Bayesian Estimated Response Rate	0.378 BE proportion of participants Standard Deviation 0.042	0.409 BE proportion of participants Standard Deviation 0.045	0.413 BE proportion of participants Standard Deviation 0.044

SECONDARY outcome

Timeframe: Month 24

Population: 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.

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. The average response rate (proportion of participants with response presented as BE) was based upon the average of multiple Bayesian simulations.

Outcome measures

Measure	Rexlemestrocel-L n=143 Participants 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).	Rexlemestrocel-L + HA n=129 Participants 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).	Placebo n=132 Participants Participants received saline solution as matching-placebo on Day 0 (Visit 2).
Effectiveness Based on Treatment Success at 24 Months: Bayesian Estimated Response Rate	0.353 BE proportion of participants Standard Deviation 0.042	0.425 BE proportion of participants Standard Deviation 0.045	0.391 BE proportion of participants Standard Deviation 0.045

SECONDARY outcome

Timeframe: Month 24

Population: 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.

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. The average response rate (proportion of participants with response presented as BE) was based upon the average of multiple Bayesian simulations.

Outcome measures

Measure	Rexlemestrocel-L n=143 Participants 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).	Rexlemestrocel-L + HA n=129 Participants 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).	Placebo n=132 Participants Participants received saline solution as matching-placebo on Day 0 (Visit 2).
Effectiveness Based on Minimal Pain Responders at 24 Months: Bayesian Estimated Response Rate	0.384 BE proportion of participants Standard Deviation 0.043	0.495 BE proportion of participants Standard Deviation 0.047	0.438 BE proportion of participants Standard Deviation 0.046

SECONDARY outcome

Timeframe: Up to Month 24

Population: 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.

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. Kaplan-Meier estimates for the probability (expressed as a percentage) of participants to receive an intervention are presented.

Outcome measures

Measure	Rexlemestrocel-L n=143 Participants 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).	Rexlemestrocel-L + HA n=129 Participants 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).	Placebo n=132 Participants Participants received saline solution as matching-placebo on Day 0 (Visit 2).
Effectiveness Based on Time to First Intervention Over 24 Months	0.1099 percentage probability	0.1003 percentage probability	0.0913 percentage probability

SECONDARY outcome

Timeframe: Month 24

Population: 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.

A minimal disability 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. The average response rate (proportion of participants with response presented as BE) was based upon the average of multiple Bayesian simulations.

Outcome measures

Measure	Rexlemestrocel-L n=143 Participants 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).	Rexlemestrocel-L + HA n=129 Participants 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).	Placebo n=132 Participants Participants received saline solution as matching-placebo on Day 0 (Visit 2).
Effectiveness Based on Minimal Disability Responders at 24 Months: Bayesian Estimated Response Rate	0.394 BE proportion of participants Standard Deviation 0.043	0.367 BE proportion of participants Standard Deviation 0.045	0.440 BE proportion of participants Standard Deviation 0.045

OTHER_PRE_SPECIFIED outcome

Timeframe: Months 1, 3, 6, 12, 18, 24, and 36

Population: 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. Number analyzed is the number of participants with data available for analysis at the given time point.

Pain intensity was recorded on a horizontal 100 mm VAS and measured as the distance in millimeters from the left origin of the horizontal VAS line and the point indicated by the participant as representing their level of pain. A horizontal 100 mm VAS anchored on the left with the words "No Pain" and on the right with the words "Worst Possible Pain", was used to measure low back pain intensity. Scores were obtained by measuring the distance in millimeters from the left origin of the line (0) to the point indicated with a slash placed by the participant to indicate the participant's level of pain. VAS ranges from 0 to 100, with higher scores indicating worst possible pain. A negative change from baseline indicates improvement.

Outcome measures

Measure	Rexlemestrocel-L n=143 Participants 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).	Rexlemestrocel-L + HA n=129 Participants 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).	Placebo n=132 Participants Participants received saline solution as matching-placebo on Day 0 (Visit 2).
Mean Change From Baseline in Low Back Pain Visual Analog Scale (VAS) Score at 1, 3, 6, 12, 18, 24, and 36 Months Change from Baseline at Month 1	-13.6 score on a scale Standard Error 2.14	-17.3 score on a scale Standard Error 2.30	-13.9 score on a scale Standard Error 2.32
Mean Change From Baseline in Low Back Pain Visual Analog Scale (VAS) Score at 1, 3, 6, 12, 18, 24, and 36 Months Change from Baseline at Month 3	-19.1 score on a scale Standard Error 2.26	-22.5 score on a scale Standard Error 2.41	-17.6 score on a scale Standard Error 2.40
Mean Change From Baseline in Low Back Pain Visual Analog Scale (VAS) Score at 1, 3, 6, 12, 18, 24, and 36 Months Change from Baseline at Month 6	-22.4 score on a scale Standard Error 2.34	-24.9 score on a scale Standard Error 2.51	-18.6 score on a scale Standard Error 2.48
Mean Change From Baseline in Low Back Pain Visual Analog Scale (VAS) Score at 1, 3, 6, 12, 18, 24, and 36 Months Change from Baseline at Month 12	-23.3 score on a scale Standard Error 2.38	-27.4 score on a scale Standard Error 2.55	-19.0 score on a scale Standard Error 2.51
Mean Change From Baseline in Low Back Pain Visual Analog Scale (VAS) Score at 1, 3, 6, 12, 18, 24, and 36 Months Change from Baseline at Month 18	-23.7 score on a scale Standard Error 2.56	-25.1 score on a scale Standard Error 2.74	-19.2 score on a scale Standard Error 2.70
Mean Change From Baseline in Low Back Pain Visual Analog Scale (VAS) Score at 1, 3, 6, 12, 18, 24, and 36 Months Change from Baseline at Month 24	-20.8 score on a scale Standard Error 2.55	-25.9 score on a scale Standard Error 2.74	-18.3 score on a scale Standard Error 2.70
Mean Change From Baseline in Low Back Pain Visual Analog Scale (VAS) Score at 1, 3, 6, 12, 18, 24, and 36 Months Change from Baseline at Month 36	-22.9 score on a scale Standard Error 2.62	-25.1 score on a scale Standard Error 2.81	-19.0 score on a scale Standard Error 2.77

Adverse Events

Rexlemestrocel-L

Serious events: 17 serious events

Other events: 111 other events

Deaths: 0 deaths

Rexlemestrocel-L + HA

Serious events: 15 serious events

Other events: 100 other events

Deaths: 0 deaths

Placebo

Serious events: 10 serious events

Other events: 98 other events

Deaths: 0 deaths

Serious adverse events

Measure	Rexlemestrocel-L n=140 participants at risk 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).	Rexlemestrocel-L + HA n=128 participants at risk 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).	Placebo n=130 participants at risk Participants received saline solution as matching-placebo on Day 0 (Visit 2).
Infections and infestations Appendicitis	1.4% 2/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.78% 1/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.77% 1/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Infections and infestations Diverticulitis	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.78% 1/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Infections and infestations Escherichia bacteremia	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.77% 1/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Infections and infestations Pneumonia	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.78% 1/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Infections and infestations Pyelonephritis acute	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.77% 1/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	3.1% 4/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.78% 1/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Cardiac disorders Acute myocardial infarction	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	1.6% 2/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Cardiac disorders Angina pectoris	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Cardiac disorders Coronary artery disease	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.78% 1/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Cardiac disorders Myocardial infarction	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	1.6% 2/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Injury, poisoning and procedural complications Cartilage injury	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Injury, poisoning and procedural complications Fall	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.77% 1/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Injury, poisoning and procedural complications Femur fracture	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Injury, poisoning and procedural complications Patella fracture	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.78% 1/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Injury, poisoning and procedural complications Road traffic accident	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Nervous system disorders Migraine	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.78% 1/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Nervous system disorders Neuralgia	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.77% 1/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Nervous system disorders Perineurial cyst	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Nervous system disorders Radiculopathy	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Nervous system disorders Sacral radiculopathy	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Nervous system disorders Seizure	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.78% 1/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Nervous system disorders Spinal meningeal cyst	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Gastrointestinal disorders Small intestinal obstruction	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Hepatobiliary disorders Biliary dyskinesia	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Hepatobiliary disorders Hepatic hematoma	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.77% 1/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Product Issues Device breakage	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Psychiatric disorders Suicidal ideation	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.78% 1/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Respiratory, thoracic and mediastinal disorders Pneumothorax spontaneous	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.78% 1/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Infections and infestations Postoperative wound infection	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Injury, poisoning and procedural complications Ankle fracture	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Nervous system disorders Headache	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.77% 1/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Gastrointestinal disorders Eosinophilic oesophagitis	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.78% 1/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Investigations	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.77% 1/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Influenza b virus test positive	0.00% 0/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.77% 1/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Surgical and medical procedures Hip surgery	0.71% 1/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	0.00% 0/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.

Other adverse events

Measure	Rexlemestrocel-L n=140 participants at risk 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).	Rexlemestrocel-L + HA n=128 participants at risk 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).	Placebo n=130 participants at risk Participants received saline solution as matching-placebo on Day 0 (Visit 2).
Musculoskeletal and connective tissue disorders Back pain	36.4% 51/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	43.8% 56/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	36.9% 48/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Musculoskeletal and connective tissue disorders Pain in extremity	13.6% 19/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	13.3% 17/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	14.6% 19/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Musculoskeletal and connective tissue disorders Arthralgia	9.3% 13/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	11.7% 15/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	10.0% 13/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Musculoskeletal and connective tissue disorders Muscle spasms	7.1% 10/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	5.5% 7/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	7.7% 10/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Musculoskeletal and connective tissue disorders Neck pain	3.6% 5/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	4.7% 6/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	7.7% 10/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Nervous system disorders Hypoesthesia	7.1% 10/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	6.2% 8/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	9.2% 12/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Nervous system disorders Paresthesia	7.9% 11/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	3.9% 5/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	3.1% 4/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.
Gastrointestinal disorders Nausea	3.6% 5/140 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	5.5% 7/128 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.	3.1% 4/130 • Up to approximately 38 months 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 (Non-serious) Adverse Events: Safety Analysis Set included all participants who were randomized and received treatment, and classified according to the actual treatment received.

Additional Information

Christopher James, VP Head of Clinical Operations

Mesoblast, Inc.

Phone: 212-880-2060

Email: Christopher.James@Mesoblast.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER