Trial Outcomes & Findings for Study of Cingal® and Triamcinolone Hexacetonide for the Relief of Knee Osteoarthritis Pain (NCT NCT04231318)

NCT ID: NCT04231318

Last Updated: 2023-08-09

Results Overview

The change from Baseline in knee pain post-treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal arm to the TH arm, the Cingal arm to the Placebo arm, and the TH arm to the Placebo arm. WOMAC Pain is a validated 100 mm visual analog scale (VAS) from 0 mm = No Pain to 100 mm = Highest Pain Level. A negative value for the change from Baseline indicates improvement in the WOMAC Pain Score, i.e. less pain post-treatment. A larger negative value indicates lower pain levels and a better outcome.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 231 participants
• Primary outcome timeframe: 26 Weeks
• Results posted on: 2023-08-09

Participant Flow

Participant milestones

Measure	Cingal Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/ml) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/ml) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) Single injection of a 1 ml dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo Single injection of a 4 ml unit dose of Placebo containing 0.9% saline
Overall Study STARTED	99	99	33
Overall Study COMPLETED	99	99	33
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Cingal® and Triamcinolone Hexacetonide for the Relief of Knee Osteoarthritis Pain

Baseline characteristics by cohort

Measure	Cingal n=99 Participants Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/mL) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/mL) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 Participants Single injection of a 1 ml dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo n=33 Participants Single injection of a 4 ml dose of Placebo containing 0.9% saline	Total n=231 Participants Total of all reporting groups
Age, Continuous	59.3 years STANDARD_DEVIATION 8.6 • n=5 Participants	58.7 years STANDARD_DEVIATION 9.6 • n=7 Participants	60.5 years STANDARD_DEVIATION 11.3 • n=5 Participants	59.2 years STANDARD_DEVIATION 9.4 • n=4 Participants
Sex: Female, Male Female	64 Participants n=5 Participants	59 Participants n=7 Participants	18 Participants n=5 Participants	141 Participants n=4 Participants
Sex: Female, Male Male	35 Participants n=5 Participants	40 Participants n=7 Participants	15 Participants n=5 Participants	90 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	5 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	25 Participants n=5 Participants	31 Participants n=7 Participants	10 Participants n=5 Participants	66 Participants n=4 Participants
Race (NIH/OMB) White	70 Participants n=5 Participants	64 Participants n=7 Participants	23 Participants n=5 Participants	157 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Index Knee Index Knee - Right	52 Participants n=5 Participants	45 Participants n=7 Participants	14 Participants n=5 Participants	111 Participants n=4 Participants
Index Knee Index Knee - Left	47 Participants n=5 Participants	54 Participants n=7 Participants	19 Participants n=5 Participants	120 Participants n=4 Participants

PRIMARY outcome

Timeframe: 26 Weeks

Population: Intent To Treat (ITT)

The change from Baseline in knee pain post-treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal arm to the TH arm, the Cingal arm to the Placebo arm, and the TH arm to the Placebo arm. WOMAC Pain is a validated 100 mm visual analog scale (VAS) from 0 mm = No Pain to 100 mm = Highest Pain Level. A negative value for the change from Baseline indicates improvement in the WOMAC Pain Score, i.e. less pain post-treatment. A larger negative value indicates lower pain levels and a better outcome.

Outcome measures

Measure	Cingal n=99 Participants Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/ml) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/ml) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 Participants Single injection of a 1 ml unit dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo n=33 Participants Single injection a 4 ml unit dose of Placebo containing 0.9% saline
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score	-44.3 score on a scale Standard Deviation 21.6	-37.5 score on a scale Standard Deviation 22.9	-36.1 score on a scale Standard Deviation 27.8

PRIMARY outcome

Timeframe: 18 Weeks

Population: Intent To Treat (ITT)

The change from Baseline in knee pain post-treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal arm to the TH arm, the Cingal arm to the Placebo arm, and the TH arm to the Placebo arm. WOMAC Pain is a validated 100 mm visual analog scale (VAS) from 0 mm = No Pain to 100 mm = Highest Pain Level. A negative number for the change from Baseline indicates improvement in the WOMAC Pain Score, i.e. less pain post-treatment.

Outcome measures

Measure	Cingal n=99 Participants Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/ml) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/ml) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 Participants Single injection of a 1 ml unit dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo n=33 Participants Single injection a 4 ml unit dose of Placebo containing 0.9% saline
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score	-44.5 score on a scale Standard Deviation 21.0	-40.2 score on a scale Standard Deviation 23.0	-36.7 score on a scale Standard Deviation 27.0

PRIMARY outcome

Timeframe: 12 Weeks

Population: Intent To Treat (ITT)

The change from Baseline in knee pain post-treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal arm to the TH arm, the Cingal arm to the Placebo arm, and the TH arm to the Placebo arm. WOMAC Pain is a validated 100 mm visual analog scale (VAS) from 0 mm = No Pain to 100 mm = Highest Pain Level. A negative number for the change from Baseline indicates improvement in the WOMAC Pain Score, i.e. less pain post-treatment.

Outcome measures

Measure	Cingal n=99 Participants Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/ml) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/ml) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 Participants Single injection of a 1 ml unit dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo n=33 Participants Single injection a 4 ml unit dose of Placebo containing 0.9% saline
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score	-44.1 score on a scale Standard Deviation 22.4	-38.9 score on a scale Standard Deviation 24.5	-37.4 score on a scale Standard Deviation 25.6

PRIMARY outcome

Timeframe: 6 Weeks

Population: Intent To Treat (ITT)

The change from Baseline in knee pain post-treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal arm to the TH arm, the Cingal arm to the Placebo arm, and the TH arm to the Placebo arm. WOMAC Pain is a validated 100 mm visual analog scale (VAS) from 0 mm = No Pain to 100 mm = Highest Pain Level. A negative number for the change from Baseline indicates improvement in the WOMAC Pain Score, i.e. less pain post-treatment.

Outcome measures

Measure	Cingal n=99 Participants Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/ml) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/ml) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 Participants Single injection of a 1 ml unit dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo n=33 Participants Single injection a 4 ml unit dose of Placebo containing 0.9% saline
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score	-46.0 score on a scale Standard Deviation 23.0	-40.4 score on a scale Standard Deviation 24.1	-36.2 score on a scale Standard Deviation 25.1

PRIMARY outcome

Timeframe: 3 Weeks

Population: Intent To Treat (ITT)

The change from Baseline in knee pain post-treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal arm to the TH arm, the Cingal arm to the Placebo arm, and the TH arm to the Placebo arm. WOMAC Pain is a validated 100 mm visual analog scale (VAS) from 0 mm = No Pain to 100 mm = Highest Pain Level. A negative number for the change from Baseline indicates improvement in the WOMAC Pain Score, i.e. less pain post-treatment.

Outcome measures

Measure	Cingal n=99 Participants Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/ml) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/ml) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 Participants Single injection of a 1 ml unit dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo n=33 Participants Single injection a 4 ml unit dose of Placebo containing 0.9% saline
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score	-45.1 score on a scale Standard Deviation 21.1	-37.7 score on a scale Standard Deviation 25.9	-34.0 score on a scale Standard Deviation 25.5

PRIMARY outcome

Timeframe: 1 Week

Population: Intent To Treat (ITT)

The change from Baseline in knee pain post-treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score comparing the Cingal arm to the TH arm, the Cingal arm to the Placebo arm, and the TH arm to the Placebo arm. WOMAC Pain is a validated 100 mm visual analog scale (VAS) from 0 mm = No Pain to 100 mm = Highest Pain Level. A negative number for the change from Baseline indicates improvement in the WOMAC Pain Score, i.e. less pain post-treatment.

Outcome measures

Measure	Cingal n=99 Participants Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/ml) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/ml) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 Participants Single injection of a 1 ml unit dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo n=33 Participants Single injection a 4 ml unit dose of Placebo containing 0.9% saline
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Score	-40.9 score on a scale Standard Deviation 22.4	-35.6 score on a scale Standard Deviation 24.7	-24.8 score on a scale Standard Deviation 25.4

SECONDARY outcome

Timeframe: 26 Weeks

Population: Intent To Treat (ITT)

The post-treatment responder rate is determined through a calculation defined by the Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index. The OMERACT-OARSI Responder Index reports the percentage of subjects that met the criteria to be a good responder to treatment. The criteria for response are (1) improvement in pain or physical function >50% and an absolute change >20 mm; or (2) improvement of >20% with an absolute change >10 mm in at least of the following three categories: pain, physical function, and patient's global assessment.

A higher percentage of subjects responding indicates a better outcome.

OMERACT-OARSI responder rates were compared between the Cingal, TH and Placebo arms.

Outcome measures

Measure	Cingal n=99 Participants Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/ml) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/ml) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 Participants Single injection of a 1 ml unit dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo n=33 Participants Single injection a 4 ml unit dose of Placebo containing 0.9% saline
The Outcomes Measures for Rheumatic Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index	89.9 percentage of participants	80.8 percentage of participants	78.8 percentage of participants

SECONDARY outcome

Timeframe: 26 Weeks

Population: Intent To Treat (ITT)

Change in knee pain was obtained from participant responses using a 100 mm Visual Analog Scale (VAS) Pain Score at each time point. This VAS scale ranged from 0 mm = No Pain to 100 mm = Highest Pain Level. A negative value for the change in pain indicates less pain post-treatment. A larger negative value indicates a higher level of improvement, and a better outcome.

Outcome measures

Measure	Cingal n=99 Participants Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/ml) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/ml) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 Participants Single injection of a 1 ml unit dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo n=33 Participants Single injection a 4 ml unit dose of Placebo containing 0.9% saline
Change From Baseline in Knee Pain as Measured by Visual Analog Scale (VAS) Pain Score	-35.1 score on a scale Standard Deviation 26.0	-31.9 score on a scale Standard Deviation 25.4	-27.1 score on a scale Standard Deviation 31.5

SECONDARY outcome

Timeframe: 26 Weeks

Population: Intent To Treat (ITT)

Change in knee pain was obtained from participant responses using a Numerical Rating Scale (NRS) Pain Score. This NRS Pain Score ranged from 0 = No Pain to 10 = Highest Pain Level. A negative value for the change in Pain Score indicates less pain post-treatment. A larger negative value indicates a higher level of improvement, and a better outcome.

Outcome measures

Measure	Cingal n=99 Participants Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/ml) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/ml) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 Participants Single injection of a 1 ml unit dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo n=33 Participants Single injection a 4 ml unit dose of Placebo containing 0.9% saline
Change From Baseline in Knee Pain as Measured by Numerical Rating Scale (NRS) Pain Score	-3.5 score on a scale Standard Deviation 2.5	-3.3 score on a scale Standard Deviation 2.3	-2.3 score on a scale Standard Deviation 3.1

SECONDARY outcome

Timeframe: 26 Weeks

Population: Intent To Treat (ITT)

The change from Baseline in knee function post-treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Function Score comparing the Cingal, TH, and Placebo arms. WOMAC Function Score records participant responses regarding the difficulty they have performing daily activities. The WOMAC Function Score is a validated 100 mm visual analog scale (VAS) from 0 mm = No Difficulty to 100 mm = Extreme Difficulty. A negative value for the change from Baseline indicates improvement in WOMAC Function Score. A larger negative value indicates improvement in performing daily activities, and a better outcome.

Outcome measures

Measure	Cingal n=99 Participants Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/ml) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/ml) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 Participants Single injection of a 1 ml unit dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo n=33 Participants Single injection a 4 ml unit dose of Placebo containing 0.9% saline
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Function Score	-40.8 score on a scale Standard Deviation 23.5	-37.5 score on a scale Standard Deviation 22.8	-35.2 score on a scale Standard Deviation 26.5

SECONDARY outcome

Timeframe: 26 Weeks

Population: Intent To Treat (ITT)

The change from Baseline in knee stiffness post-treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Score comparing the Cingal, TH, and Placebo arms. WOMAC Stiffness Score records participant responses regarding the sensation of ease in moving their joint. The WOMAC Stiffness Score is a validated 100 mm visual analog scale (VAS) from 0 mm = No Stiffness to 100 mm = Extreme Stiffness. A negative value for the change from Baseline indicates improvement in WOMAC Stiffness Score. A larger negative value indicates less stiffness, and a better outcome.

Outcome measures

Measure	Cingal n=99 Participants Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/ml) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/ml) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 Participants Single injection of a 1 ml unit dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo n=33 Participants Single injection a 4 ml unit dose of Placebo containing 0.9% saline
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Stiffness Score	-39.4 score on a scale Standard Deviation 26.0	-34.6 score on a scale Standard Deviation 25.9	-32.1 score on a scale Standard Deviation 29.1

SECONDARY outcome

Timeframe: 26 Weeks

Population: Intent To Treat (ITT)

The change from Baseline in overall clinical improvement in the knee post-treatment as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score comparing the Cingal, TH, and Placebo arms. WOMAC Total Score combines the three 0-to-100 point scores from the WOMAC Pain Score, the WOMAC Stiffness Score, and the WOMAC Function Score to calculate a TOTAL Score from 0 = No Symptoms to 100 = Highest Degrees of Pain, Stiffness and Functional Limitation Symptoms.

A negative value for the change from Baseline in WOMAC Total Score indicates reduction in pain, stiffness, and improved function. A larger negative value indicates a better overall clinical outcome.

Outcome measures

Measure	Cingal n=99 Participants Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/ml) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/ml) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 Participants Single injection of a 1 ml unit dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo n=33 Participants Single injection a 4 ml unit dose of Placebo containing 0.9% saline
Change From Baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Total Score	-41.4 score on a scale Standard Deviation 22.4	-37.3 score on a scale Standard Deviation 22.4	-35.6 score on a scale Standard Deviation 26.2

SECONDARY outcome

Timeframe: 26 Weeks

Population: Intent To Treat (ITT)

The change from Baseline in knee pain post-treatment as measured by the Patient Global Assessment (PGA) Score comparing the Cingal, TH, and Placebo arms. PGA Score records participant responses to their assessment of how much their STUDY (treated) knee is bothering them today . The PGA Score is a validated 100 mm visual analog scale (VAS) from 0 mm = No Pain to 100 mm = Extreme Pain.

A negative value for the change from Baseline indicates improvement in PGA Score. A larger negative value indicates less pain, and a better clinical outcome.

Outcome measures

Measure	Cingal n=99 Participants Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/ml) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/ml) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 Participants Single injection of a 1 ml unit dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo n=33 Participants Single injection a 4 ml unit dose of Placebo containing 0.9% saline
Change From Baseline in the Patient Global Assessment (PGA) Score	-42.3 score on a scale Standard Deviation 27.3	-37.6 score on a scale Standard Deviation 25.3	-34.0 score on a scale Standard Deviation 28.8

SECONDARY outcome

Timeframe: 26 Weeks

Population: Intent To Treat (ITT)

The change from Baseline in knee pain post-treatment as measured by the Evaluator Global Assessment (EGA) Score comparing the Cingal, TH, and Placebo arms. EGA Score records the Study Evaluator's assessment of how much the patient's STUDY (treated) knee is bothering them today . The EGA Score is a validated 100 mm visual analog scale (VAS) from 0 mm = No Pain to 100 mm = Extreme Pain.

A negative value for the change from Baseline indicates improvement in EGA Score. A larger negative value indicates less pain, and a better clinical outcome.

Outcome measures

Measure	Cingal n=99 Participants Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/ml) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/ml) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 Participants Single injection of a 1 ml unit dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo n=33 Participants Single injection a 4 ml unit dose of Placebo containing 0.9% saline
Change From Baseline in the Evaluator Global Assessment (EGA) Score	-40.1 score on a scale Standard Deviation 25.8	-33.3 score on a scale Standard Deviation 26.0	-32.6 score on a scale Standard Deviation 24.9

SECONDARY outcome

Timeframe: 26 Weeks

Population: Intent To Treat (ITT)

The usage of Rescue Medication (RM) as based on the average number of acetominophen/paracetamol pills taken among participants at 26 Weeks post treatment comparing between the Cingal, Triamcinolone Hexacetonide (TH) and Placebo arms.

A smaller value in average RM indicates that fewer pills were taken by the participants, which may correlate to a better clinical outcome in terms of pain.

Outcome measures

Measure	Cingal n=99 Participants Single injection of a 4 ml unit dose of Cingal containing 88 mg (22 mg/ml) of cross-linked sodium hyaluronate and 18 mg (4.5 mg/ml) of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 Participants Single injection of a 1 ml unit dose of Triamcinolone Hexacetonide (TH) containing 20 mg/ml TH	Placebo n=33 Participants Single injection a 4 ml unit dose of Placebo containing 0.9% saline
The Usage of Rescue Medication (Acetaminophen/Paracetamol) at 26 Weeks	8.5 Pills Standard Deviation 26.1	14.2 Pills Standard Deviation 31.1	19.1 Pills Standard Deviation 40.0

Adverse Events

Cingal

Serious events: 1 serious events

Other events: 58 other events

Deaths: 0 deaths

Triamcinolone Hexacetonide (TH)

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Cingal n=99 participants at risk Single injection of chemically cross-linked sodium hyaluronate supplied as a 4 mL unit dose with a nominal 18 mg of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 participants at risk Single injection of TH 20 mg/ml supplied as 1 mL unit dose	Placebo n=33 participants at risk Single injection of 0.9% saline supplied as a 4 mL unit dose
Respiratory, thoracic and mediastinal disorders Hypoxia	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Psychiatric disorders Delerium	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).

Other adverse events

Measure	Cingal n=99 participants at risk Single injection of chemically cross-linked sodium hyaluronate supplied as a 4 mL unit dose with a nominal 18 mg of triamcinolone hexacetonide (TH)	Triamcinolone Hexacetonide (TH) n=99 participants at risk Single injection of TH 20 mg/ml supplied as 1 mL unit dose	Placebo n=33 participants at risk Single injection of 0.9% saline supplied as a 4 mL unit dose
General disorders Injection site haematoma	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
General disorders Injection Site irritation	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
General disorders Injection site joint pain	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
General disorders Injection site pain	2.0% 2/99 • Number of events 2 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	2.0% 2/99 • Number of events 2 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Endocrine disorders Hypothyroidism	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Gastrointestinal disorders Abdominal pain upper	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Gastrointestinal disorders Diarrhoea	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Gastrointestinal disorders Nausea	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	3.0% 1/33 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
General disorders Oedema peripheral	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
General disorders Pain	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
General disorders Peripheral swelling	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Immune system disorders Seasonal allergy	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Infections and infestations Abcess limb	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Infections and infestations Bacterial food poisoning	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Infections and infestations Bronchitis	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Infections and infestations Bursitis infective	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Infections and infestations COVID-19	2.0% 2/99 • Number of events 2 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	3.0% 1/33 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Infections and infestations Cellulitis	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Infections and infestations Ear infection	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Infections and infestations Herpes zoster	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Infections and infestations Hordeolum	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Infections and infestations Localized infection	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Infections and infestations Pneumonia	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Infections and infestations Tooth infection	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Infections and infestations Urinary tract infection	4.0% 4/99 • Number of events 4 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Injury, poisoning and procedural complications Arthropod sting	2.0% 2/99 • Number of events 2 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Injury, poisoning and procedural complications Contusion	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Injury, poisoning and procedural complications Fall	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Injury, poisoning and procedural complications Joint injury	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Injury, poisoning and procedural complications Ligament sprain	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Injury, poisoning and procedural complications Muscle strain	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Injury, poisoning and procedural complications Radius fracture	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Injury, poisoning and procedural complications Suture related complication	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Injury, poisoning and procedural complications Synovial rupture	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Injury, poisoning and procedural complications Thermal burn	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Musculoskeletal and connective tissue disorders Arthralgia	6.1% 6/99 • Number of events 6 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	5.1% 5/99 • Number of events 5 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	6.1% 2/33 • Number of events 2 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Musculoskeletal and connective tissue disorders Back pain	2.0% 2/99 • Number of events 2 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	3.0% 1/33 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Musculoskeletal and connective tissue disorders Bursitis	2.0% 2/99 • Number of events 2 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Musculoskeletal and connective tissue disorders Groin pain	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Musculoskeletal and connective tissue disorders Joint effusion	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Musculoskeletal and connective tissue disorders Joint stiffness	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Musculoskeletal and connective tissue disorders Osteoarthritis	2.0% 2/99 • Number of events 2 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Musculoskeletal and connective tissue disorders Pain in extremity	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Musculoskeletal and connective tissue disorders Spinal stenosis	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Musculoskeletal and connective tissue disorders Synovial cyst	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Musculoskeletal and connective tissue disorders Synovitis	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Musculoskeletal and connective tissue disorders Vertebral foraminal stenosis	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Nervous system disorders Carpal tunnel syndrome	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Nervous system disorders Headache	3.0% 3/99 • Number of events 3 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Nervous system disorders Sciatica	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Nervous system disorders Syncope	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Nervous system disorders Transient global amnesia	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Psychiatric disorders Depression	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Psychiatric disorders Insomnia	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Renal and urinary disorders Nephrolithiasis	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Reproductive system and breast disorders Breast fibrosis	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Vascular disorders Hypertension	1.0% 1/99 • Number of events 1 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).
Musculoskeletal and connective tissue disorders Joint swelling	3.0% 3/99 • Number of events 3 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/99 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).	0.00% 0/33 • Adverse Events were collected from the time of the Baseline Study Visit until Study Completion at 26 Weeks. The definitions of adverse events and serious adverse events is the same as used in the clinicaltrials.gov definitions. The incidence, timing, severity, and relationship to treatment of all Adverse Events (AE) were collected and coded using Medical Dictionary for Regulatory Activities (MedDRA).

Additional Information

Kara Mezger, Executive Director Clinical Affairs

Anika Therapeutics

Phone: 781.457.9000

Email: kmezger@anika.com

Results disclosure agreements

• Principal investigator is a sponsor employee PI shall not publish Index or the WOMAC® User Guide in any publication, on the Internet or any other public access medium. NICHOLAS BELLAMY, MD, MSc, DSc, MBA, FRACP shall be acknowledged as the source of the Index. Results at the Institution shall not be made before the first multi-site publication by Sponsor. If no multi-site publication within18 months after the Trial completion, PI has right to publish and or present its results (but not the results of any other site) from the Trial.
• Publication restrictions are in place

Restriction type: OTHER