Trial Outcomes & Findings for An Efficacy and Safety Study of Two Doses of Intra-Articular Ampion Injection for Pain of Osteoarthritis of the Knee (NCT NCT01839331)

Last Updated: 2022-06-30

Results Overview

Mean Change in WOMAC A Pain (Western Ontario and McMaster Universities Arthritis Index) score from Baseline to 12 weeks. 5-point Likert scale (0=none to 4=extreme). A negative difference constitutes a decrease in pain with a greater negative value indicating a greater reduction in pain.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

329 participants

Primary outcome timeframe

Scored at Baseline and 12 weeks

Results posted on

2022-06-30

Participant Flow

Recruitment of subjects occurred in medical clinics during the months of March, April, and May 2013.

No pharmacological or non-pharmacological treatment targeting OA started or changed during the 4 weeks prior to randomization or likely to be changed during the duration of the study.

Unit of analysis: Single knee

Participant milestones

Participant milestones
Measure	Ampion 4 mL Dose 4 mL Injection of Ampion	Placebo 4 mL Dose 4 mL Injection of Placebo	Ampion 10 mL Dose 10 mL Injection of Ampion	Placebo 10 mL Dose 10 mL Injection of Placebo
Overall Study STARTED	83 83	83 83	82 82	81 81
Overall Study Week 6	83 83	83 83	82 82	81 81
Overall Study COMPLETED	79 79	77 77	77 77	76 76
Overall Study NOT COMPLETED	4 4	6 6	5 5	5 5

Reasons for withdrawal

Reasons for withdrawal
Measure	Ampion 4 mL Dose 4 mL Injection of Ampion	Placebo 4 mL Dose 4 mL Injection of Placebo	Ampion 10 mL Dose 10 mL Injection of Ampion	Placebo 10 mL Dose 10 mL Injection of Placebo
Overall Study Early Termination	3	0	1	2
Overall Study Protocol Violation	1	6	4	3

Baseline Characteristics

An Efficacy and Safety Study of Two Doses of Intra-Articular Ampion Injection for Pain of Osteoarthritis of the Knee

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ampion 4 mL Dose n=83 Participants 4 mL Injection of Ampion	Placebo 4 mL Dose n=83 Participants 4 mL Injection of Placebo	Ampion 10 mL Dose n=82 Participants 10 mL Injection of Ampion	Placebo 10 mL Dose n=81 Participants 10 mL Injection of Placebo	Total n=329 Participants Total of all reporting groups
Age, Continuous	62.7 years STANDARD_DEVIATION 9.27 • n=5 Participants	60.7 years STANDARD_DEVIATION 8.27 • n=7 Participants	62.8 years STANDARD_DEVIATION 8.36 • n=5 Participants	63.8 years STANDARD_DEVIATION 9.95 • n=4 Participants	62.48 years STANDARD_DEVIATION 9.02 • n=21 Participants
Sex: Female, Male Female	56 Participants n=5 Participants	57 Participants n=7 Participants	46 Participants n=5 Participants	50 Participants n=4 Participants	209 Participants n=21 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	26 Participants n=7 Participants	36 Participants n=5 Participants	31 Participants n=4 Participants	120 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	4 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	83 Participants n=5 Participants	83 Participants n=7 Participants	80 Participants n=5 Participants	79 Participants n=4 Participants	325 Participants n=21 Participants
Ethnicity (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	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 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	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	4 Participants n=4 Participants	29 Participants n=21 Participants
Race (NIH/OMB) White	74 Participants n=5 Participants	74 Participants n=7 Participants	74 Participants n=5 Participants	77 Participants n=4 Participants	299 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 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	0 Participants n=21 Participants
Region of Enrollment United States	83 participants n=5 Participants	83 participants n=7 Participants	82 participants n=5 Participants	81 participants n=4 Participants	329 participants n=21 Participants
Weight (kg)	95.6 kg STANDARD_DEVIATION 22.15 • n=5 Participants	98.4 kg STANDARD_DEVIATION 25.28 • n=7 Participants	95.2 kg STANDARD_DEVIATION 22.42 • n=5 Participants	90.6 kg STANDARD_DEVIATION 22.07 • n=4 Participants	94.98 kg STANDARD_DEVIATION 23.08 • n=21 Participants
BMI (kg/m^2)	33.2 kg/m^2 STANDARD_DEVIATION 7.76 • n=5 Participants	34.5 kg/m^2 STANDARD_DEVIATION 8.02 • n=7 Participants	32.8 kg/m^2 STANDARD_DEVIATION 6.58 • n=5 Participants	32.1 kg/m^2 STANDARD_DEVIATION 6.46 • n=4 Participants	33.16 kg/m^2 STANDARD_DEVIATION 7.27 • n=21 Participants
Kellgren-Lawrence (KL) Grade Kellgren-Lawrence Grade II	28 Participants n=5 Participants	29 Participants n=7 Participants	32 Participants n=5 Participants	26 Participants n=4 Participants	115 Participants n=21 Participants
Kellgren-Lawrence (KL) Grade Kellgren-Lawrence Grade III	38 Participants n=5 Participants	32 Participants n=7 Participants	35 Participants n=5 Participants	34 Participants n=4 Participants	139 Participants n=21 Participants
Kellgren-Lawrence (KL) Grade Kellgren-Lawrence Grade IV	17 Participants n=5 Participants	22 Participants n=7 Participants	15 Participants n=5 Participants	21 Participants n=4 Participants	75 Participants n=21 Participants
WOMAC Pain	2.22 score on a scale STANDARD_DEVIATION 0.490 • n=5 Participants	2.32 score on a scale STANDARD_DEVIATION 0.548 • n=7 Participants	2.19 score on a scale STANDARD_DEVIATION 0.512 • n=5 Participants	2.23 score on a scale STANDARD_DEVIATION 0.602 • n=4 Participants	2.24 score on a scale STANDARD_DEVIATION 0.54 • n=21 Participants
WOMAC Stiffness	2.25 score on a scale STANDARD_DEVIATION 0.717 • n=5 Participants	2.36 score on a scale STANDARD_DEVIATION 0.798 • n=7 Participants	2.43 score on a scale STANDARD_DEVIATION 0.781 • n=5 Participants	2.44 score on a scale STANDARD_DEVIATION 0.768 • n=4 Participants	2.37 score on a scale STANDARD_DEVIATION 0.77 • n=21 Participants
WOMAC Function	2.13 score on a scale STANDARD_DEVIATION 0.564 • n=5 Participants	2.25 score on a scale STANDARD_DEVIATION 0.626 • n=7 Participants	2.23 score on a scale STANDARD_DEVIATION 0.610 • n=5 Participants	2.22 score on a scale STANDARD_DEVIATION 0.616 • n=4 Participants	2.21 score on a scale STANDARD_DEVIATION 0.60 • n=21 Participants
Patient's Global Assessment (PGA)	3.35 score on a scale STANDARD_DEVIATION 0.652 • n=5 Participants	3.40 score on a scale STANDARD_DEVIATION 0.811 • n=7 Participants	3.35 score on a scale STANDARD_DEVIATION 0.822 • n=5 Participants	3.42 score on a scale STANDARD_DEVIATION 0.652 • n=4 Participants	3.38 score on a scale STANDARD_DEVIATION 0.76 • n=21 Participants

PRIMARY outcome

Timeframe: Scored at Baseline and 12 weeks

Population: Intent to Treat (ITT)

Outcome measures

Outcome measures
Measure	Ampion Combined (4 mL & 10 mL Dose) n=165 Participants Combined results of 4 mL and 10 mL Ampion dose	Placebo Combined (4 mL and 10 mL Dose) n=164 Participants Combined results of 4 mL and 10 mL Placebo dose	Ampion 4 mL Dose n=83 Participants 4 mL Injection of Ampion	Placebo 4 mL Dose n=83 Participants 4 mL Injection of Placebo	Ampion 10 mL Dose n=82 Participants 10 mL Injection of Ampion	Placebo 10 mL Dose n=81 Participants 10 mL Injection of Placebo
Change in Knee Pain	-0.93 score on a scale Interval -1.045 to -0.807	-0.72 score on a scale Interval -0.852 to -0.587	-0.93 score on a scale Interval -1.099 to -0.766	-0.71 score on a scale Interval -0.871 to -0.543	-0.92 score on a scale Interval -1.093 to -0.746	-0.73 score on a scale Interval -0.946 to -0.52

SECONDARY outcome

Timeframe: Scored at Baseline and 12 weeks.

Population: Intent to Treat (ITT)

Mean change in WOMAC C function score (Western Ontario and McMaster Universities Arthritis Index) from Baseline to 12 weeks. 5-point Likert scale indicating limitation of function (0=none to 4=extreme). A greater negative value indicates a improvement in function.

Outcome measures

Outcome measures
Measure	Ampion Combined (4 mL & 10 mL Dose) n=165 Participants Combined results of 4 mL and 10 mL Ampion dose	Placebo Combined (4 mL and 10 mL Dose) n=164 Participants Combined results of 4 mL and 10 mL Placebo dose	Ampion 4 mL Dose n=83 Participants 4 mL Injection of Ampion	Placebo 4 mL Dose n=83 Participants 4 mL Injection of Placebo	Ampion 10 mL Dose n=82 Participants 10 mL Injection of Ampion	Placebo 10 mL Dose n=81 Participants 10 mL Injection of Placebo
Change in Knee Function	-0.78 score on a scale Interval -0.901 to -0.655	-0.64 score on a scale Interval -0.766 to -0.51	-0.72 score on a scale Interval -0.899 to -0.549	-0.58 score on a scale Interval -0.735 to -0.429	-0.83 score on a scale Interval -1.007 to -0.657	-0.69 score on a scale Interval -0.903 to -0.485

SECONDARY outcome

Timeframe: Scored at Baseline and 12 weeks.

Population: Intent to Treat (ITT)

Mean Change in WOMAC B stiffness score from Baseline to 12 weeks. 5-point Likert scale (0=none to 4=extreme). A negative difference constitutes a reduction in stiffness.

Outcome measures

Outcome measures
Measure	Ampion Combined (4 mL & 10 mL Dose) n=165 Participants Combined results of 4 mL and 10 mL Ampion dose	Placebo Combined (4 mL and 10 mL Dose) n=164 Participants Combined results of 4 mL and 10 mL Placebo dose	Ampion 4 mL Dose n=83 Participants 4 mL Injection of Ampion	Placebo 4 mL Dose n=83 Participants 4 mL Injection of Placebo	Ampion 10 mL Dose n=82 Participants 10 mL Injection of Ampion	Placebo 10 mL Dose n=81 Participants 10 mL Injection of Placebo
Change in Knee Stiffness.	-0.72 score on a scale Interval -0.866 to -0.582	-0.67 score on a scale Interval -0.823 to -0.524	-0.66 score on a scale Interval -0.86 to -0.465	-0.55 score on a scale Interval -0.746 to -0.35	-0.79 score on a scale Interval -0.994 to -0.579	-0.80 score on a scale Interval -1.028 to -0.577

SECONDARY outcome

Timeframe: Scored at Baseline and 12 weeks.

Population: Intent to Treat (ITT)

Patients are asked the following question: "Considering all the ways in which your arthritis affects you, please indicate how you are doing." 5-point Likert scale (0 = very well, 1 = well, 2 = fair, 3 = poor, 4 = very poor). A negative value constitutes an improvement in patient's assessment of disease severity.

Outcome measures

Outcome measures
Measure	Ampion Combined (4 mL & 10 mL Dose) n=165 Participants Combined results of 4 mL and 10 mL Ampion dose	Placebo Combined (4 mL and 10 mL Dose) n=164 Participants Combined results of 4 mL and 10 mL Placebo dose	Ampion 4 mL Dose n=83 Participants 4 mL Injection of Ampion	Placebo 4 mL Dose n=83 Participants 4 mL Injection of Placebo	Ampion 10 mL Dose n=82 Participants 10 mL Injection of Ampion	Placebo 10 mL Dose n=81 Participants 10 mL Injection of Placebo
Change in Patient's Global Assessment	-0.87 score on a scale Interval -1.033 to -0.701	-0.65 score on a scale Interval -0.821 to -0.472	-0.96 score on a scale Interval -1.186 to -0.742	-0.55 score on a scale Interval -0.801 to -0.308	-0.77 score on a scale Interval -1.018 to -0.519	-0.74 score on a scale Interval -0.992 to -0.489

Adverse Events

Ampion 4 mL Dose

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Placebo 4 mL Dose

Serious events: 2 serious events

Other events: 38 other events

Deaths: 0 deaths

Ampion 10 mL Dose

Serious events: 3 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo 10 mL Dose

Serious events: 2 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ampion 4 mL Dose n=83 participants at risk 4 mL Injection of Ampion	Placebo 4 mL Dose n=83 participants at risk 4 mL Injection of Placebo	Ampion 10 mL Dose n=82 participants at risk 10 mL Injection of Ampion	Placebo 10 mL Dose n=81 participants at risk 10 mL Injection of Placebo
Cardiac disorders Bradycardia	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	1.2% 1/82 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/81 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
General disorders Chest Discomfort	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	1.2% 1/82 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/81 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
General disorders Chest Pain	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	1.2% 1/82 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/81 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
Infections and infestations Arthritis Bacterial	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/82 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	1.2% 1/81 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
Infections and infestations Osteomyelitis	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/82 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	1.2% 1/81 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
Renal and urinary disorders Renal Failure Acute	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	1.2% 1/83 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/82 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/81 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
Skin and subcutaneous tissue disorders Dermatitis Allergic	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	1.2% 1/83 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/82 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/81 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.

Other adverse events

Additional Information

Dr. Howard Levy / Chief Medical Officer

Ampio Pharmaceuticals

Phone: 720-437-6500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Ampion 4 mL Dose n=83 participants at risk 4 mL Injection of Ampion	Placebo 4 mL Dose n=83 participants at risk 4 mL Injection of Placebo	Ampion 10 mL Dose n=82 participants at risk 10 mL Injection of Ampion	Placebo 10 mL Dose n=81 participants at risk 10 mL Injection of Placebo
Injury, poisoning and procedural complications Ligament Sprain	2.4% 2/83 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	2.4% 2/83 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/82 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	1.2% 1/81 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
Musculoskeletal and connective tissue disorders Arthralgia	6.0% 5/83 • Number of events 5 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	19.3% 16/83 • Number of events 16 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	7.3% 6/82 • Number of events 6 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	9.9% 8/81 • Number of events 8 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
Nervous system disorders Headache	3.6% 3/83 • Number of events 3 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	3.6% 3/83 • Number of events 3 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	1.2% 1/82 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	1.2% 1/81 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
General disorders Injection Site Pain	3.6% 3/83 • Number of events 3 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	3.6% 3/83 • Number of events 3 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	2.4% 2/82 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	3.7% 3/81 • Number of events 3 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
Infections and infestations Sinusitis	2.4% 2/83 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	2.4% 2/83 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	1.2% 1/82 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	3.7% 3/81 • Number of events 3 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
Injury, poisoning and procedural complications Fall	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	2.4% 2/83 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/82 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	4.9% 4/81 • Number of events 4 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
Infections and infestations Upper Respiratory Infection	2.4% 2/83 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	2.4% 2/83 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	1.2% 1/82 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/81 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
Musculoskeletal and connective tissue disorders Joint Stiffness	1.2% 1/83 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	3.6% 3/83 • Number of events 3 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	2.4% 2/82 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/81 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
Musculoskeletal and connective tissue disorders Joint Swelling	1.2% 1/83 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	1.2% 1/83 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	2.4% 2/82 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	2.5% 2/81 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
Infections and infestations Gastroenteritis	1.2% 1/83 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	1.2% 1/83 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/82 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	2.5% 2/81 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
Musculoskeletal and connective tissue disorders Muscle Spasms	1.2% 1/83 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	1.2% 1/83 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/82 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	2.5% 2/81 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
General disorders Oedema Peripheral	2.4% 2/83 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/82 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	1.2% 1/81 • Number of events 1 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
General disorders Chest Pain	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	2.4% 2/82 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/81 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	2.4% 2/83 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/82 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/81 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.
Infections and infestations Gastroenteritis Viral	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/83 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	0.00% 0/82 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.	2.5% 2/81 • Number of events 2 • 12 Weeks Patients will be followed for the occurrence of Adverse Events (AEs) until 12 weeks after the first dose of study medication and additionally for AEs in the study knee for those patients who opt to continue in the 20 week follow-up visit.