NCT02412735: MSB-DR003

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

Completed Phase 3 Results posted Last updated 19 October 2022

What this trial tests

Phase 3 trial testing Rexlemestrocel-L in Degenerative Disc Disease in 404 participants. Completed in 15 June 2021.

Timeline

6 March 2015

Primary endpoint
15 May 2020

15 June 2021

Quick facts

Lead sponsor	Mesoblast, Ltd.
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	404
Start date	6 March 2015
Primary completion	15 May 2020
Estimated completion	15 June 2021
Sites	48 locations across United States, Australia

Drugs / interventions tested

• Rexlemestrocel-L — full drug profile →
• Rexlemestrocel-L + HA Mixture — full drug profile →
• Placebo

Conditions studied

• Degenerative Disc Disease — all drugs for Degenerative Disc Disease →

Sponsor

Mesoblast, Ltd. — full company profile →

Who can join

18 and older, any sex, with Degenerative Disc Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Treatment Success: Bayesian Estimated Response Rate Primary · Up to 24 months

Overall treatment success was determined based on number of responders who had composite response at both months 12 and 24 evaluated per specified criteria. A treatment responder with treatment success was defined as a participant who met the 3 criteria of a composite responder analysis as: 50% or greater reduction in the lower-back pain visual analogue scale (VAS) score; 15-point or greater reduction in the Oswestry Disability Index (ODI) score; and lack of post-treatment interventions at the treated level as of the study visit (Visits 6 \[12 months post-treatment\] and 8 \[24 months post-tre

Group	Value	95% CI
Rexlemestrocel-L	0.267	± 0.038
Rexlemestrocel-L + HA	0.335	± 0.043
Placebo	0.313	± 0.041

Effectiveness Based on Pain Responders: Bayesian Estimated Response Rate Secondary · Up to 24 months

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

Group	Value	95% CI
Rexlemestrocel-L	0.352	± 0.041
Rexlemestrocel-L + HA	0.472	± 0.045
Placebo	0.388	± 0.044

Effectiveness Based on Functional Responders: Bayesian Estimated Response Rate Secondary · Up to 24 months

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

Group	Value	95% CI
Rexlemestrocel-L	0.378	± 0.042
Rexlemestrocel-L + HA	0.409	± 0.045
Placebo	0.413	± 0.044

Effectiveness Based on Treatment Success at 24 Months: Bayesian Estimated Response Rate Secondary · Month 24

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

Group	Value	95% CI
Rexlemestrocel-L	0.353	± 0.042
Rexlemestrocel-L + HA	0.425	± 0.045
Placebo	0.391	± 0.045

Effectiveness Based on Minimal Pain Responders at 24 Months: Bayesian Estimated Response Rate Secondary · Month 24

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

Group	Value	95% CI
Rexlemestrocel-L	0.384	± 0.043
Rexlemestrocel-L + HA	0.495	± 0.047
Placebo	0.438	± 0.046

Effectiveness Based on Time to First Intervention Over 24 Months Secondary · Up to Month 24

The effectiveness of the study drug was evaluated based on its ability in increasing the time to additional interventions at the treated level over 24 months post-treatment. Kaplan-Meier estimates for the probability (expressed as a percentage) of participants to receive an intervention are presented.

Group	Value	95% CI
Rexlemestrocel-L	0.1099
Rexlemestrocel-L + HA	0.1003
Placebo	0.0913

Effectiveness Based on Minimal Disability Responders at 24 Months: Bayesian Estimated Response Rate Secondary · Month 24

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.

Group	Value	95% CI
Rexlemestrocel-L	0.394	± 0.043
Rexlemestrocel-L + HA	0.367	± 0.045
Placebo	0.440	± 0.045

Mean Change From Baseline in Low Back Pain Visual Analog Scale (VAS) Score at 1, 3, 6, 12, 18, 24, and 36 Months Secondary · Months 1, 3, 6, 12, 18, 24, and 36

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 pai

Change from Baseline at Month 1

Group	Value	95% CI
Rexlemestrocel-L	-13.6	± 2.14
Rexlemestrocel-L + HA	-17.3	± 2.30
Placebo	-13.9	± 2.32

Change from Baseline at Month 3

Group	Value	95% CI
Rexlemestrocel-L	-19.1	± 2.26
Rexlemestrocel-L + HA	-22.5	± 2.41
Placebo	-17.6	± 2.40

Change from Baseline at Month 6

Group	Value	95% CI
Rexlemestrocel-L	-22.4	± 2.34
Rexlemestrocel-L + HA	-24.9	± 2.51
Placebo	-18.6	± 2.48

Change from Baseline at Month 12

Group	Value	95% CI
Rexlemestrocel-L	-23.3	± 2.38
Rexlemestrocel-L + HA	-27.4	± 2.55
Placebo	-19.0	± 2.51

Change from Baseline at Month 18

Group	Value	95% CI
Rexlemestrocel-L	-23.7	± 2.56
Rexlemestrocel-L + HA	-25.1	± 2.74
Placebo	-19.2	± 2.70

Change from Baseline at Month 24

Group	Value	95% CI
Rexlemestrocel-L	-20.8	± 2.55
Rexlemestrocel-L + HA	-25.9	± 2.74
Placebo	-18.3	± 2.70

Change from Baseline at Month 36

Group	Value	95% CI
Rexlemestrocel-L	-22.9	± 2.62
Rexlemestrocel-L + HA	-25.1	± 2.81
Placebo	-19.0	± 2.77

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 38 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Rexlemestrocel-L

Serious: 17/140 (12%)

Deaths: 0/143

Rexlemestrocel-L + HA

Serious: 15/128 (12%)

Deaths: 0/129

Placebo

Serious: 10/130 (8%)

Deaths: 0/132

Serious adverse events (40 terms)

Reaction	System	Rexlemestrocel-L	Rexlemestrocel-L + HA	Placebo
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Appendicitis	Infections and infestations	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—
Diverticulitis	Infections and infestations	—	—	—
Escherichia bacteremia	Infections and infestations	—	—	—
Pneumonia	Infections and infestations	—	—	—
Pyelonephritis acute	Infections and infestations	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—
Angina pectoris	Cardiac disorders	—	—	—
Coronary artery disease	Cardiac disorders	—	—	—
Cartilage injury	Injury, poisoning and procedural complications	—	—	—
Fall	Injury, poisoning and procedural complications	—	—	—
Femur fracture	Injury, poisoning and procedural complications	—	—	—
Patella fracture	Injury, poisoning and procedural complications	—	—	—
Road traffic accident	Injury, poisoning and procedural complications	—	—	—
Migraine	Nervous system disorders	—	—	—
Neuralgia	Nervous system disorders	—	—	—
Perineurial cyst	Nervous system disorders	—	—	—
Radiculopathy	Nervous system disorders	—	—	—
Sacral radiculopathy	Nervous system disorders	—	—	—
Seizure	Nervous system disorders	—	—	—
Spinal meningeal cyst	Nervous system disorders	—	—	—

Other adverse events (8 terms — click to expand)

Reaction	System	Rexlemestrocel-L	Rexlemestrocel-L + HA	Placebo
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Hypoesthesia	Nervous system disorders	—	—	—
Paresthesia	Nervous system disorders	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—
Neck pain	Musculoskeletal and connective tissue disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—

Most-reported serious reactions: Back pain, Appendicitis, Acute myocardial infarction, Myocardial infarction, Diverticulitis, Escherichia bacteremia, Pneumonia, Pyelonephritis acute.

Data from ClinicalTrials.gov NCT02412735 adverse events section.

Sponsor's own description

This is a prospective, multicenter, randomized, double-blind, placebo-controlled Phase 3 study designed to evaluate the safety and efficacy of Mesoblast's rexlemestrocel-L alone or combined with hyaluronic acid (HA) in participants with chronic low back pain (\> 6 months) associated with moderate radiographic degenerative changes of a disc.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities.
   Galipeau J, Sensébé L. · · 2018 · cited 1288× · PMID 29859173 · DOI 10.1016/j.stem.2018.05.004
2. Intervertebral Disc Degeneration: Biomaterials and Tissue Engineering Strategies toward Precision Medicine.
   Mohd Isa IL, Mokhtar SA, Abbah SA, Fauzi MB, et al · · 2022 · cited 101× · PMID 35373924 · DOI 10.1002/adhm.202102530
3. Cell therapy for intervertebral disc repair: Clinical perspective.
   Sakai D, Schol J. · · 2017 · cited 89× · PMID 29662795 · DOI 10.1016/j.jot.2017.02.002
4. Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: Recommendations of the ORS spine section.
   Smith LJ, Silverman L, Sakai D, Le Maitre CL, et al · · 2018 · cited 82× · PMID 30895277 · DOI 10.1002/jsp2.1036
5. Treatment of chronic low back pain - new approaches on the horizon.
   Knezevic NN, Mandalia S, Raasch J, Knezevic I, et al · · 2017 · cited 72× · PMID 28546769 · DOI 10.2147/jpr.s132769
6. Trends in clinical trials for articular cartilage repair by cell therapy.
   Negoro T, Takagaki Y, Okura H, Matsuyama A. · · 2018 · cited 71× · PMID 30345076 · DOI 10.1038/s41536-018-0055-2
7. Immuno-Modulatory Effects of Intervertebral Disc Cells.
   Bermudez-Lekerika P, Crump KB, Tseranidou S, Nüesch A, et al · · 2022 · cited 63× · PMID 35846355 · DOI 10.3389/fcell.2022.924692
8. Stem Cells and Intervertebral Disc Regeneration Overview-What They Can and Can't Do.
   Vadalà G, Ambrosio L, Russo F, Papalia R, et al · · 2021 · cited 47× · PMID 34376495 · DOI 10.14444/8054