Trial Outcomes & Findings for Randomized Study of the Efficacy and Safety of a Single Dose of Synvisc-One® in Chinese Patients With Symptomatic Osteoarthritis of the Knee (NCT NCT03190369)

NCT ID: NCT03190369

Last Updated: 2022-03-25

Results Overview

The WOMAC Numerical Rating Scale (NRS) version 3.1 questionnaire was a self-administered, health status measure questionnaire of 24 questions comprising 3 subscales (joint pain, stiffness and physical function) for participants with Osteoarthritis (OA) of the knee. WOMAC A1 pain subscale (measure of pain during walking on a flat surface) was measured on 11-point (NRS) ranging from 0 (none) to 10 (extreme), where lower score represented no pain and higher score represented extreme pain.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

440 participants

Primary outcome timeframe

From Baseline up to Week 26

Results posted on

2022-03-25

Participant Flow

The study was conducted at 21 sites in China from 21 August 2017 to 28 January 2019. A total of 524 participants were screened, of which, 84 participants were screen failures. Screen failures were mainly due to inclusion criteria not met.

A total of 440 participants were enrolled and randomized in the study. Assignment to arms was done centrally using an interactive voice response system/interactive web response system (IVRS/IWRS) in 1:1 ratio (Placebo: Hylan G-F 20).

Participant milestones

Participant milestones
Measure	Placebo Participants received a single intra-articular (IA) injection of phosphate buffered saline on Day 1 and were observed for 26 weeks.	Hylan G-F 20 Participants received a single IA injection of 6 mL Hylan G-F 20 (Synvisc-One) on Day 1 and were observed for 26 weeks.
Overall Study STARTED	220	220
Overall Study Treated	220	218
Overall Study COMPLETED	219	212
Overall Study NOT COMPLETED	1	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received a single intra-articular (IA) injection of phosphate buffered saline on Day 1 and were observed for 26 weeks.	Hylan G-F 20 Participants received a single IA injection of 6 mL Hylan G-F 20 (Synvisc-One) on Day 1 and were observed for 26 weeks.
Overall Study Poor compliance to protocol	0	1
Overall Study Withdraw before treatment	1	5
Overall Study Randomized but not treated	0	2

Baseline Characteristics

Randomized Study of the Efficacy and Safety of a Single Dose of Synvisc-One® in Chinese Patients With Symptomatic Osteoarthritis of the Knee

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=220 Participants Participants received a single IA injection of phosphate buffered saline on Day 1 and were observed for 26 weeks.	Hylan G-F 20 n=220 Participants Participants received a single IA injection of 6 mL Hylan G-F 20 (Synvisc-One) on Day 1 and were observed for 26 weeks.	Total n=440 Participants Total of all reporting groups
Age, Continuous	61.6 years STANDARD_DEVIATION 7.8 • n=5 Participants	61.5 years STANDARD_DEVIATION 7.9 • n=7 Participants	61.5 years STANDARD_DEVIATION 7.9 • n=5 Participants
Sex: Female, Male Female	172 Participants n=5 Participants	170 Participants n=7 Participants	342 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	50 Participants n=7 Participants	98 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	220 Participants n=5 Participants	220 Participants n=7 Participants	440 Participants n=5 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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Baseline up to Week 26

Population: Analysis was performed on modified Intent-To-Treat (mITT) population which included all randomized and treated participants. Participants were analyzed in the treatment group to which they were randomized.

Outcome measures

Outcome measures
Measure	Placebo n=220 Participants Participants received a single IA injection of phosphate buffered saline on Day 1 and were observed for 26 weeks.	Hylan G-F 20 n=218 Participants Participants received a single IA injection of 6 mL Hylan G-F 20 (Synvisc-One) on Day 1 and were observed for 26 weeks.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Pain (Walking Pain) Subscale Score Over 26 Weeks	-2.271 score on a scale Standard Error 0.110	-2.146 score on a scale Standard Error 0.108

SECONDARY outcome

Timeframe: From Baseline up to Week 26

Population: Analysis was performed on mITT population.

The WOMAC NRS version 3.1 questionnaire was a self-administered, health status measure questionnaire of 24 questions comprising 3 subscales (joint pain, stiffness and physical function) for participants with OA of the knee. WOMAC A1 pain subscale (measure of pain during walking on a flat surface) was measured on 11-point (NRS) ranging from 0 (none) to 10 (extreme), where lower score represented no pain and higher score represented extreme pain. For 7-day average WOMAC A1, the baseline value was defined as the average of the WOMAC A1 scores recorded 7 days prior to the first investigational medicinal product (IMP) administration (WOMAC A1 score recorded on Day 1 included). The 7-day average WOMAC A1 was set as missing if 3 or more of the 7 WOMAC A1 scores were missing.

Outcome measures

Outcome measures
Measure	Placebo n=220 Participants Participants received a single IA injection of phosphate buffered saline on Day 1 and were observed for 26 weeks.	Hylan G-F 20 n=218 Participants Participants received a single IA injection of 6 mL Hylan G-F 20 (Synvisc-One) on Day 1 and were observed for 26 weeks.
Change From Baseline in 7-day Average WOMAC A1 Pain (Walking Pain) Subscale Score Over 26 Weeks	-2.275 score on a scale Standard Error 0.108	-2.176 score on a scale Standard Error 0.106

SECONDARY outcome

Timeframe: From Baseline up to Week 26

Population: Analysis was performed on mITT population.

The WOMAC NRS version 3.1 questionnaire was a self-administered, health status measure questionnaire of 24 questions comprising 3 subscales (joint pain, stiffness and physical function) for participants with OA of the knee. WOMAC A (5 items: measure of pain while walking, using stairs, at night while in bed, sitting or lying, and standing); each item was measured on 11-point (NRS) ranging from 0 (none) to 10 (extreme), where lower score represented no pain and higher score represented extreme pain. Total WOMAC A score was the sum of 5 item scores and ranges from 0 (none) to 50 (extreme); where lower score represented no pain and higher score represented extreme pain.

Outcome measures

Outcome measures
Measure	Placebo n=220 Participants Participants received a single IA injection of phosphate buffered saline on Day 1 and were observed for 26 weeks.	Hylan G-F 20 n=218 Participants Participants received a single IA injection of 6 mL Hylan G-F 20 (Synvisc-One) on Day 1 and were observed for 26 weeks.
Change From Baseline in WOMAC A Score Over 26 Weeks	-8.747 score on a scale Standard Error 0.491	-8.621 score on a scale Standard Error 0.486

SECONDARY outcome

Timeframe: From Baseline up to Week 26

Population: Analysis was performed on mITT population.

PTGA (self-assessment of target knee OA condition) was measured using an 11-point NRS ranging from 0 (best possible) to 10 (worst possible), where lower score represented best possible condition and higher score represented worst possible condition.

Outcome measures

Outcome measures
Measure	Placebo n=220 Participants Participants received a single IA injection of phosphate buffered saline on Day 1 and were observed for 26 weeks.	Hylan G-F 20 n=218 Participants Participants received a single IA injection of 6 mL Hylan G-F 20 (Synvisc-One) on Day 1 and were observed for 26 weeks.
Change From Baseline in Patient Global Self-Assessment (PTGA) Score of Osteoarthritis Over 26 Weeks	-2.138 score on a scale Standard Error 0.104	-2.144 score on a scale Standard Error 0.102

SECONDARY outcome

Timeframe: From Baseline up to Week 26

Population: Analysis was performed on mITT population.

COGA was used by the physicians to perform a global assessment of the participant's target knee OA condition. The response was captured using the 11-point NRS pain intensity rating scale ranging from 0 (best possible) to 10 (worst possible) at the specified time points, where lower score represented best possible condition and higher score represented worst possible condition.

Outcome measures

Outcome measures
Measure	Placebo n=220 Participants Participants received a single IA injection of phosphate buffered saline on Day 1 and were observed for 26 weeks.	Hylan G-F 20 n=218 Participants Participants received a single IA injection of 6 mL Hylan G-F 20 (Synvisc-One) on Day 1 and were observed for 26 weeks.
Change From Baseline in Clinical Observer Global Assessment (COGA) Score of Osteoarthritis Over 26 Weeks	-2.145 score on a scale Standard Error 0.095	-2.225 score on a scale Standard Error 0.094

SECONDARY outcome

Timeframe: Week 4, Week 8, Week 12, Week 16, Week 20 and Week 26

Population: Analysis was performed on mITT population.

WOMAC A1 responder were defined as \>=2-point improvement from baseline in the WOMAC A1 NRS. The WOMAC NRS version 3.1 questionnaire was a self-administered, health status measure questionnaire of 24 questions comprising 3 subscales (joint pain, stiffness and physical function) for participants with OA of the knee. WOMAC A1 pain subscale (measure of pain during walking on a flat surface) was measured on 11-point (NRS) ranging from 0 (none) to 10 (extreme), where lower score represented no pain and higher score represented extreme pain.

Outcome measures

Outcome measures
Measure	Placebo n=220 Participants Participants received a single IA injection of phosphate buffered saline on Day 1 and were observed for 26 weeks.	Hylan G-F 20 n=218 Participants Participants received a single IA injection of 6 mL Hylan G-F 20 (Synvisc-One) on Day 1 and were observed for 26 weeks.
Percentage of Positive WOMAC A1 Responder Over 26 Weeks Week 4	58.6 percentage of participants	53.2 percentage of participants
Percentage of Positive WOMAC A1 Responder Over 26 Weeks Week 8	65.0 percentage of participants	62.4 percentage of participants
Percentage of Positive WOMAC A1 Responder Over 26 Weeks Week 12	66.4 percentage of participants	62.8 percentage of participants
Percentage of Positive WOMAC A1 Responder Over 26 Weeks Week 16	69.1 percentage of participants	63.3 percentage of participants
Percentage of Positive WOMAC A1 Responder Over 26 Weeks Week 20	65.0 percentage of participants	66.5 percentage of participants
Percentage of Positive WOMAC A1 Responder Over 26 Weeks Week 26	68.2 percentage of participants	67.0 percentage of participants

SECONDARY outcome

Timeframe: From Baseline up to Week 26

Population: Analysis was performed on safety population which included randomized participants who received at least 1 injection or part of an injection of Hylan G-F 20 or placebo.

Adverse Event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAEs were defined as AEs that developed, worsened (according to the Investigator opinion), or became serious during the on-treatment period (time from the injection of IMP up to Week 26 follow-up visit).

Outcome measures

Outcome measures
Measure	Placebo n=220 Participants Participants received a single IA injection of phosphate buffered saline on Day 1 and were observed for 26 weeks.	Hylan G-F 20 n=218 Participants Participants received a single IA injection of 6 mL Hylan G-F 20 (Synvisc-One) on Day 1 and were observed for 26 weeks.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	142 Participants	134 Participants

Adverse Events

Placebo

Serious events: 10 serious events

Other events: 66 other events

Deaths: 0 deaths

Hylan G-F 20

Serious events: 14 serious events

Other events: 75 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=220 participants at risk Participants received a single IA injection of phosphate buffered saline on Day 1 and were observed for 26 weeks.	Hylan G-F 20 n=218 participants at risk Participants received a single IA injection of 6 mL Hylan G-F 20 (Synvisc-One) on Day 1 and were observed for 26 weeks.
Infections and infestations Nasopharyngitis	5.5% 12/220 • Number of events 18 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	6.0% 13/218 • Number of events 14 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Infections and infestations Upper Respiratory Tract Infection	13.6% 30/220 • Number of events 40 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	12.8% 28/218 • Number of events 31 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Gastrointestinal disorders Toothache	3.6% 8/220 • Number of events 9 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	5.0% 11/218 • Number of events 16 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Arthralgia	10.9% 24/220 • Number of events 29 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	11.9% 26/218 • Number of events 35 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Joint Swelling	1.8% 4/220 • Number of events 5 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	7.3% 16/218 • Number of events 18 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=220 participants at risk Participants received a single IA injection of phosphate buffered saline on Day 1 and were observed for 26 weeks.	Hylan G-F 20 n=218 participants at risk Participants received a single IA injection of 6 mL Hylan G-F 20 (Synvisc-One) on Day 1 and were observed for 26 weeks.
Infections and infestations Bronchitis	0.00% 0/220 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.46% 1/218 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Infections and infestations Hepatitis B	0.45% 1/220 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.00% 0/218 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Infections and infestations Pneumonia	0.91% 2/220 • Number of events 2 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.92% 2/218 • Number of events 2 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Cancer	0.00% 0/220 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.46% 1/218 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Adenocarcinoma	0.00% 0/220 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.46% 1/218 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian Fibroma	0.00% 0/220 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.46% 1/218 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal Cancer	0.00% 0/220 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.46% 1/218 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal Cell Carcinoma	0.00% 0/220 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.46% 1/218 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Metabolism and nutrition disorders Type 2 Diabetes Mellitus	0.45% 1/220 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.00% 0/218 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Nervous system disorders Cerebral Infarction	0.45% 1/220 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.46% 1/218 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Nervous system disorders Lacunar Infarction	0.00% 0/220 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.46% 1/218 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Cardiac disorders Arteriosclerosis Coronary Artery	0.00% 0/220 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.46% 1/218 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Vascular disorders Hypertension	0.45% 1/220 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.92% 2/218 • Number of events 2 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Gastrointestinal disorders Abdominal Adhesions	0.00% 0/220 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.46% 1/218 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Intervertebral Disc Protrusion	0.45% 1/220 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.00% 0/218 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Lumbar Spinal Stenosis	0.00% 0/220 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.46% 1/218 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Spinal Osteoarthritis	0.45% 1/220 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.46% 1/218 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Reproductive system and breast disorders Uterine Polyp	0.45% 1/220 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.00% 0/218 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Injury, poisoning and procedural complications Joint Injury	0.45% 1/220 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.00% 0/218 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Injury, poisoning and procedural complications Ligament Sprain	0.00% 0/220 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.46% 1/218 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
Injury, poisoning and procedural complications Radius Fracture	0.45% 1/220 • Number of events 1 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.	0.00% 0/218 • AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit. Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.