Trial Outcomes & Findings for A Safety and Efficacy Study of Anti-inflammatory (Canakinumab) and Cartilage Stimulating (LNA043) Drugs Injected Into the Knee Joint of Participants With Knee Osteoarthritis (OA) (NCT NCT04814368)

Results Overview

Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in volume of cartilage in the index region. The index region was defined as the union of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

23 participants

Primary outcome timeframe

Baseline, Day 197

Results posted on

2025-10-24

Participant Flow

Participants took part in 11 investigative sites in 6 countries.

The study consisted of 4 screening visits (Screening 1-4), of which Screening 2 and 4 could be performed remotely.

Participant milestones

Participant milestones
Measure	Placebo to ACZ885+LNA043 40 mg Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg + LNA043 40 mg ACZ885 600 mg single dose i.a. followed by LNA043 40 mg administrated i.a every four weeks, three times.	ACZ885 600 mg ACZ885 600 mg single dose intra-articular.
Overall Study STARTED	3	9	3	8
Overall Study COMPLETED	2	4	3	6
Overall Study NOT COMPLETED	1	5	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo to ACZ885+LNA043 40 mg Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg + LNA043 40 mg ACZ885 600 mg single dose i.a. followed by LNA043 40 mg administrated i.a every four weeks, three times.	ACZ885 600 mg ACZ885 600 mg single dose intra-articular.
Overall Study Study Terminated by Sponsor	0	3	0	2
Overall Study Subject Decision	1	2	0	0

Baseline Characteristics

A Safety and Efficacy Study of Anti-inflammatory (Canakinumab) and Cartilage Stimulating (LNA043) Drugs Injected Into the Knee Joint of Participants With Knee Osteoarthritis (OA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo to ACZ885+LNA043 40 mg n=3 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=9 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg + LNA043 40 mg n=3 Participants ACZ885 600 mg single dose i.a. followed by LNA043 40 mg administrated i.a every four weeks, three times.	ACZ885 600 mg n=8 Participants ACZ885 600 mg single dose intra-articular.	Total n=23 Participants Total of all reporting groups
Age, Continuous	66.3 years STANDARD_DEVIATION 10.97 • n=5 Participants	61.1 years STANDARD_DEVIATION 5.90 • n=7 Participants	59.3 years STANDARD_DEVIATION 7.02 • n=5 Participants	61.8 years STANDARD_DEVIATION 8.55 • n=4 Participants	61.8 years STANDARD_DEVIATION 7.43 • n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	7 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants	16 Participants n=21 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	7 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian or other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized White	3 Participants n=5 Participants	9 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	21 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, Day 197

Population: Participants in the pharmacodynamic (PD) analysis set from the arms "Placebo to ACZ885+LNA043 40 mg" and "Placebo to ACZ885" who had an available value for the outcome measure. The PD analysis set included all participants with available PD data and no protocol deviations with relevant impact on PD data.

Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in volume of cartilage in the index region. The index region was defined as the union of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=2 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=5 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg ACZ885 600 mg single dose intra-articular.
Change in Cartilage Volume in the Index Region Measured by MRI at Day 197 (Placebo to ACZ885+LNA043 Versus Placebo to ACZ885)	108.33 µL Standard Deviation 226.451	-26.13 µL Standard Deviation 65.204	—

PRIMARY outcome

Timeframe: Baseline, Day 85

Population: Participants in the pharmacodynamic (PD) analysis set from the arms "ACZ885 600 mg" and "Placebo to ACZ885" who had an available value for the outcome measure. The PD analysis set included all participants with available PD data and no protocol deviations with relevant impact on PD data.

The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales. One of those is the KOOS pain consisting of 9 questions with a recall of 7days. Each question has 5 standardized answer options with a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=8 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=7 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg ACZ885 600 mg single dose intra-articular.
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale (ACZ885 Versus Placebo to ACZ885)	22.2 score on scale Standard Deviation 20.09	13.9 score on scale Standard Deviation 13.89	—

SECONDARY outcome

Timeframe: From pre-dose up to Day 365

Population: Participants in the pharmacokinetic (PK) analysis set from the arms "Placebo to ACZ885+LNA043 40 mg" and "ACZ885 600mg + LNA043 40mg" who had an available value for the outcome measure. The PK analysis set included all participants who received any study drug, and had at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, and for whom there were no protocol deviations with impact on PK data.

To evaluate the immunogenicity of LNA043 via validated ligand-binding assay of potential anti-LNA043 antibodies.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=3 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=3 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg ACZ885 600 mg single dose intra-articular.
Number of Participants With Anti-LNA043 Antibodies (Placebo to ACZ885+LNA043 Versus ACZ885 + LNA043)	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Pre-dose Day 1, Day 15, Day 43 and 60 minutes after first injection of LNA043 on Day 15

Population: Participants in the pharmacokinetic (PK) analysis set from the arms "Placebo to ACZ885+LNA043 40 mg" and "ACZ885 600mg + LNA043 40mg" who had an available value for the outcome measure. The PK analysis set included all participants who received any study drug, and had at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, and for whom there were no protocol deviations with impact on PK data.

ANGPTL3 is a protein that is primarily involved in the lipid metabolism but has recently been shown to have chondrogenic and chondroprotective effects. Cmax is defined as the maximum (peak) observed concentration following a dose. ANGPTL3 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8 or higher). ANGPTL3 was determined by a validated ligand binding assay; the anticipated LLOQ is 39.7 pmol/L in serum.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=2 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=3 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg ACZ885 600 mg single dose intra-articular.
Maximum Serum Concentration (Cmax) of ANGPTL3 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043)	16.2 ng/mL Standard Deviation 2.47	24.1 ng/mL Standard Deviation 7.32	—

SECONDARY outcome

Timeframe: Pre-dose on Days 1, 15, 43, and 71

Population: Participants in the pharmacokinetic (PK) analysis set from the arms "Placebo to ACZ885+LNA043 40 mg" and "ACZ885 600mg + LNA043 40mg" who had an available value for the outcome measure. The PK analysis set included all participants who received any study drug, and had at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, and for whom there were no protocol deviations with impact on PK data.

ANGPTL3 is a protein that is primarily involved in the lipid metabolism but has recently been shown to have chondrogenic and chondroprotective effects. ANGPTL3 was measured in synovial fluid.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=1 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=1 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg ACZ885 600 mg single dose intra-articular.
Synovial Fluid Concentrations of ANGPTL3 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043) Day 1	NA ng/mL Standard Deviation NA NA = not measurable, below the lower limit of quantification of 2.74 ng/mL	NA ng/mL Standard Deviation NA NA = not measurable, below the lower limit of quantification of 2.74 ng/mL	—
Synovial Fluid Concentrations of ANGPTL3 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043) Day 15	NA ng/mL Standard Deviation NA NA = not measurable, below the lower limit of quantification of 2.74 ng/mL	NA ng/mL Standard Deviation NA NA = not measurable, below the lower limit of quantification of 2.74 ng/mL	—
Synovial Fluid Concentrations of ANGPTL3 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043) Day 43	NA ng/mL Standard Deviation NA NA = not measurable, below the lower limit of quantification of 2.74 ng/mL	NA ng/mL Standard Deviation NA NA = not measurable, below the lower limit of quantification of 2.74 ng/mL	—
Synovial Fluid Concentrations of ANGPTL3 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043) Day 71	NA ng/mL Standard Deviation NA NA = not measurable, below the lower limit of quantification of 2.74 ng/mL	NA ng/mL Standard Deviation NA NA = not measurable, below the lower limit of quantification of 2.74 ng/mL	—

SECONDARY outcome

Timeframe: Day 15: pre-dose, 20, 60, 120 and 240 minutes, and 8 and 24 hours post LNA043 first injection on Day 15

Population: Participants in the pharmacokinetic (PK) analysis set from the arms "Placebo to ACZ885+LNA043 40 mg" and "ACZ885 600mg + LNA043 40mg" who had an available value for the outcome measure. The PK analysis set included all participants who received any study drug, and had at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, and for whom there were no protocol deviations with impact on PK data.

Cmax is defined as the maximum (peak) observed concentration following a dose. LNA043 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8 or higher). LNA043 was determined by a validated immuno-capture and LC-MS/MS method; the anticipated LLOQ is 10 ng/mL in serum.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=1 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=1 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg ACZ885 600 mg single dose intra-articular.
Maximum Serum Concentration (Cmax) of LNA043 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043)	120 ng/mL	149 ng/mL	—

SECONDARY outcome

Timeframe: Day 15: pre-dose, 20, 60, 120 and 240 minutes, and 8 and 24 hours post LNA043 first injection on Day 15

Population: Participants in the pharmacokinetic (PK) analysis set from the arms "Placebo to ACZ885+LNA043 40 mg" and "ACZ885 600mg + LNA043 40mg" who had an available value for the outcome measure. The PK analysis set included all participants who received any study drug, and had at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, and for whom there were no protocol deviations with impact on PK data.

Tmax is the time to reach maximum (peak) drug concentration after single-dose administration (time). LNA043 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8 or higher). LNA043 was determined by a validated immuno-capture and LC-MS/MS method; the anticipated LLOQ is 10 ng/mL in serum.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=1 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=1 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg ACZ885 600 mg single dose intra-articular.
Time to Reach Maximum Serum Concentration (Tmax) of LNA043 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043)	2 hour	4.02 hour	—

SECONDARY outcome

Timeframe: Day 15: pre-dose, 20, 60, 120 and 240 minutes, and 8 and 24 hours post LNA043 first injection on Day 15

Population: Participants in the pharmacokinetic (PK) analysis set from the arms "Placebo to ACZ885+LNA043 40 mg" and "ACZ885 600mg + LNA043 40mg" who had an available value for the outcome measure. The PK analysis set included all participants who received any study drug, and had at least one available valid (i.e. not flagged for exclusion) PK concentration measurement, and for whom there were no protocol deviations with impact on PK data.

AUClast is the area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (tlast) of LNA043. LNA043 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8 or higher). LNA043 was determined by a validated immuno-capture and LC-MS/MS method; the anticipated LLOQ is 10 ng/mL in serum.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=1 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=1 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg ACZ885 600 mg single dose intra-articular.
Area Under Serum Concentration-time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of LNA043 (Placebo to ACZ885+LNA043 Versus ACZ885+LNA043)	800 h*ng/mL	1880 h*ng/mL	—

SECONDARY outcome

Timeframe: Baseline, Day 197 and Day 365

Population: Participants in the pharmacodynamic (PD) analysis set from the arms "Placebo to ACZ885+LNA043 40 mg", "ACZ885 600 mg + LNA043 40 mg" and "ACZ885 600 mg" who had an available value for the outcome measure. The PD analysis set included all participants with available PD data and no protocol deviations with relevant impact on PD data.

Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in volume of cartilage in the index region. The index region was defined as the union of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=2 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=3 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg n=6 Participants ACZ885 600 mg single dose intra-articular.
Change in Cartilage Volume of the Index Region Measured by MRI at Day 197 and Day 365 (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 197	108.33 µL Standard Deviation 226.451	307.90 µL Standard Deviation 580.213	-82.33 µL Standard Deviation 390.645
Change in Cartilage Volume of the Index Region Measured by MRI at Day 197 and Day 365 (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 365	152.78 µL Standard Deviation 135.128	20.54 µL Standard Deviation 557.708	-129.93 µL Standard Deviation 544.793

SECONDARY outcome

Timeframe: Baseline, Day 365

Population: Participants in the pharmacodynamic (PD) analysis set from the arms "Placebo to ACZ885+LNA043 40 mg" and "Placebo to ACZ885" who had an available value for the outcome measure. The PD analysis set included all participants with available PD data and no protocol deviations with relevant impact on PD data.

Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in volume of cartilage in the index region. The index region was defined as the union of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=2 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=3 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg ACZ885 600 mg single dose intra-articular.
Change in Cartilage Volume of the Index Region Measured by MRI at Day 365 (Placebo to ACZ885+LNA043 Versus Placebo to ACZ885)	152.78 µL Standard Deviation 135.128	20.54 µL Standard Deviation 557.708	—

SECONDARY outcome

Timeframe: Baseline, Day 197 and 365

Population: Participants in the pharmacodynamic (PD) analysis set from the arms "Placebo to ACZ885+LNA043 40 mg", "ACZ885 600 mg + LNA043 40 mg" and "ACZ885 600 mg" who had an available value for the outcome measure. The PD analysis set included all participants with available PD data and no protocol deviations with relevant impact on PD data.

Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in thickness of cartilage in the index region. The index region was defined as the union of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=2 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=3 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg n=7 Participants ACZ885 600 mg single dose intra-articular.
Change in Cartilage Thickness of the Index Region Measured by MRI at Day 197 and Day 365 (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 197	0.07 mm Standard Deviation 0.083	0.13 mm Standard Deviation 0.212	-0.02 mm Standard Deviation 0.121
Change in Cartilage Thickness of the Index Region Measured by MRI at Day 197 and Day 365 (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 365	-0.03 mm Standard Deviation 0.046	0.04 mm Standard Deviation 0.168	-0.05 mm Standard Deviation 0.152

SECONDARY outcome

Timeframe: Baseline, Day 197 and 365

Population: Participants in the pharmacodynamic (PD) analysis set from the arms "Placebo to ACZ885+LNA043 40 mg" and "Placebo to ACZ885" who had an available value for the outcome measure. The PD analysis set included all participants with available PD data and no protocol deviations with relevant impact on PD data.

Magnetic resonance images (MRI) were obtained from the target knee to visualize and quantify changes in thickness of cartilage in the index region. The index region was defined as the union of the femoral medial anterior (FMA), central (FMC) and posterior (FMP) cartilage subregions in the knee.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=2 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=3 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg ACZ885 600 mg single dose intra-articular.
Change in Cartilage Thickness of the Index Region Measured by MRI at Day 197 and Day 365 (Placebo to ACZ885+LNA043 Versus Placebo to ACZ885) Day 197	0.07 mm Standard Deviation 0.083	0.06 mm Standard Deviation 0.112	—
Change in Cartilage Thickness of the Index Region Measured by MRI at Day 197 and Day 365 (Placebo to ACZ885+LNA043 Versus Placebo to ACZ885) Day 365	-0.03 mm Standard Deviation 0.046	0.11 mm Standard Deviation 0.072	—

SECONDARY outcome

Timeframe: Baseline, Day 85

Population: Participants in the pharmacodynamic (PD) analysis set from the arms "ACZ885 600 mg" and "Placebo to ACZ885" who had an available value for the outcome measure. The PD analysis set included all participants with available PD data and no protocol deviations with relevant impact on PD data.

Magnetic resonance images (MRI) were obtained from the target knee with dynamic contrast enhancement (DCE) to visualize and quantify changes in k-trans as a marker of the activity of synovial inflammation. During the DCE-MRI acquisition, while the contrast agent is preferentially taken up at sites with an increased perfusion due to the formation of new vessels with high porosity (such as the inflamed synovial membrane), a temporal variation of the MRI signal intensity occurs. When the contrast distributes through the intravascular and extravascular spaces, the MR signal intensity in the image volume elements (voxels) of the target tissue changes over time, generating so-called signal intensity (SI) curves. These curves can then be analyzed to derive parameters related to tissue perfusion. The parameter of primary interest was the volume transfer rate of the gadolinium-based contrast agent (GBCA) from the blood plasma in synovium, commonly referred to as Ktrans.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=6 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=7 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg ACZ885 600 mg single dose intra-articular.
Change in Synovitis Level Measured From Ktrans by Dynamic Contrast Enhanced MRI (DCE-MRI) (ACZ885 Versus Placebo to ACZ885)	-0.0009 min^-1 Standard Deviation 0.01185	-0.0051 min^-1 Standard Deviation 0.00702	—

SECONDARY outcome

Timeframe: Baseline, Day 15, 29, 43, 57, 71, 85

Population: Participants in the pharmacodynamic (PD) analysis set from the arms "ACZ885 600 mg" and "Placebo to ACZ885" who had an available value for the outcome measure. The PD analysis set included all participants with available PD data and no protocol deviations with relevant impact on PD data. In alignment with the study protocol, data collected beyond Day 85 for NRS pain is not part of this secondary outcome measure comparing the groups ACZ885 versus Placebo to ACZ885.

The Numerical Rating Scale (NRS) Pain is a subjective assessment in which individuals rate their pain on an eleven-point numerical scale. The scale ranges from 0 (no pain) to 10 (worst possible pain). The NRS Pain instrument had a recall period of 24 hours and the participants were asked to rate the pain intensity at its worst.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=8 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=7 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg ACZ885 600 mg single dose intra-articular.
Change in Numeric Rating Scale (NRS) Over Time (ACZ885 Versus Placebo to ACZ885) Day 71	-2.1 score on scale Standard Deviation 1.95	-3.1 score on scale Standard Deviation 2.19	—
Change in Numeric Rating Scale (NRS) Over Time (ACZ885 Versus Placebo to ACZ885) Day 15	-1.5 score on scale Standard Deviation 2.33	-2.1 score on scale Standard Deviation 2.27	—
Change in Numeric Rating Scale (NRS) Over Time (ACZ885 Versus Placebo to ACZ885) Day 29	-2.5 score on scale Standard Deviation 2.73	-3.1 score on scale Standard Deviation 1.95	—
Change in Numeric Rating Scale (NRS) Over Time (ACZ885 Versus Placebo to ACZ885) Day 43	-1.8 score on scale Standard Deviation 2.25	-2.4 score on scale Standard Deviation 2.15	—
Change in Numeric Rating Scale (NRS) Over Time (ACZ885 Versus Placebo to ACZ885) Day 57	-2.1 score on scale Standard Deviation 2.80	-3.5 score on scale Standard Deviation 2.35	—
Change in Numeric Rating Scale (NRS) Over Time (ACZ885 Versus Placebo to ACZ885) Day 85	-1.7 score on scale Standard Deviation 2.29	-2.7 score on scale Standard Deviation 2.06	—

SECONDARY outcome

Timeframe: Baseline, Day 15, 29, 43, 57, 71, 85, 197 and 365

Population: Participants in the pharmacodynamic (PD) analysis set from the arms "Placebo to ACZ885+LNA043 40 mg", "ACZ885 600 mg + LNA043 40 mg" and "ACZ885 600 mg" who had an available value for the outcome measure. The PD analysis set included all participants with available PD data and no protocol deviations with relevant impact on PD data.

The Numerical Rating Scale (NRS) Pain is a subjective assessment in which individuals rate their pain on an eleven-point numerical scale. The scale ranges from 0 (no pain) to 10 (worst possible pain). The NRS Pain instrument had a recall period of 24 hours and the participants were asked to rate the pain intensity at its worst.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=2 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=3 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg n=7 Participants ACZ885 600 mg single dose intra-articular.
Change in Numeric Rating Scale (NRS) Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 57	-4.0 score on scale	-2.0 score on scale Standard Deviation 0.00	-3.5 score on scale Standard Deviation 2.35
Change in Numeric Rating Scale (NRS) Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 15	-3.0 score on scale	-0.7 score on scale Standard Deviation 1.15	-2.1 score on scale Standard Deviation 2.27
Change in Numeric Rating Scale (NRS) Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 29	-3.0 score on scale	-1.0 score on scale Standard Deviation 1.00	-3.1 score on scale Standard Deviation 1.95
Change in Numeric Rating Scale (NRS) Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 43	-4.5 score on scale Standard Deviation 2.12	-0.7 score on scale Standard Deviation 0.58	-2.4 score on scale Standard Deviation 2.15
Change in Numeric Rating Scale (NRS) Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 71	-4.0 score on scale	-2.0 score on scale Standard Deviation 1.00	-3.1 score on scale Standard Deviation 2.19
Change in Numeric Rating Scale (NRS) Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 85	-5.5 score on scale Standard Deviation 0.71	-3.3 score on scale Standard Deviation 0.58	-2.7 score on scale Standard Deviation 2.06
Change in Numeric Rating Scale (NRS) Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 197	-6.0 score on scale	-3.3 score on scale Standard Deviation 2.08	-2.8 score on scale Standard Deviation 2.64
Change in Numeric Rating Scale (NRS) Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 365	-3.0 score on scale	-4.3 score on scale Standard Deviation 2.31	-3.0 score on scale Standard Deviation 3.83

SECONDARY outcome

Timeframe: Baseline, Day 15, 29, 43, 57, 71, 85

Population: Participants in the pharmacodynamic (PD) analysis set from the arms "ACZ885 600 mg" and "Placebo to ACZ885" who had an available value for the outcome measure. The PD analysis set included all participants with available PD data and no protocol deviations with relevant impact on PD data. In alignment with the study protocol, data collected beyond Day 85 for KOOS pain subscale is not part of this secondary outcome measure comparing the groups ACZ885 versus Placebo to ACZ885.

The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales. One of those is the KOOS pain consisting of 9 questions with a recall of 7days. Each question has 5 standardized answer options with a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=8 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=8 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg ACZ885 600 mg single dose intra-articular.
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885 Versus Placebo to ACZ885) Day 15	12.8 score on scale Standard Deviation 21.72	20.1 score on scale Standard Deviation 20.40	—
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885 Versus Placebo to ACZ885) Day 29	16.3 score on scale Standard Deviation 17.60	24.0 score on scale Standard Deviation 20.52	—
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885 Versus Placebo to ACZ885) Day 43	11.8 score on scale Standard Deviation 12.31	21.9 score on scale Standard Deviation 21.28	—
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885 Versus Placebo to ACZ885) Day 57	13.9 score on scale Standard Deviation 18.96	28.1 score on scale Standard Deviation 19.38	—
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885 Versus Placebo to ACZ885) Day 71	14.3 score on scale Standard Deviation 15.75	26.4 score on scale Standard Deviation 20.03	—
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885 Versus Placebo to ACZ885) Day 85	25.0 score on scale Standard Deviation 3.93	22.2 score on scale Standard Deviation 20.09	—

SECONDARY outcome

Timeframe: Baseline, Day 15, 29, 43, 57, 71, 85, 197 and 365

Population: Participants in the pharmacodynamic (PD) analysis set from the arms "Placebo to ACZ885+LNA043 40 mg", "ACZ885 600 mg + LNA043 40 mg" and "ACZ885 600 mg" who had an available value for the outcome measure. The PD analysis set included all participants with available PD data and no protocol deviations with relevant impact on PD data.

The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales. One of those is the KOOS pain consisting of 9 questions with a recall of 7days. Each question has 5 standardized answer options with a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=2 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=3 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg n=8 Participants ACZ885 600 mg single dose intra-articular.
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 365	31.9 score on scale Standard Deviation 17.68	45.4 score on scale Standard Deviation 10.52	31.5 score on scale Standard Deviation 26.33
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 15	25.0 score on scale Standard Deviation 27.50	3.7 score on scale Standard Deviation 18.91	20.1 score on scale Standard Deviation 20.40
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 29	36.1 score on scale Standard Deviation 19.64	15.7 score on scale Standard Deviation 9.76	24.0 score on scale Standard Deviation 20.52
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 43	25.0 score on scale Standard Deviation 15.71	15.7 score on scale Standard Deviation 16.74	21.9 score on scale Standard Deviation 21.28
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 57	25.0 score on scale Standard Deviation 7.86	17.6 score on scale Standard Deviation 5.78	28.1 score on scale Standard Deviation 19.38
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 71	29.2 score on scale Standard Deviation 5.89	16.7 score on scale Standard Deviation 2.78	26.4 score on scale Standard Deviation 20.03
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 85	25.0 score on scale Standard Deviation 3.93	22.2 score on scale Standard Deviation 14.70	22.2 score on scale Standard Deviation 20.09
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Subscale Over Time (ACZ885+LNA043 Versus ACZ885, and ACZ885+LNA043 Versus Placebo to ACZ885+LNA043) Day 197	37.5 score on scale Standard Deviation 9.82	38.0 score on scale Standard Deviation 12.83	25.0 score on scale Standard Deviation 21.87

SECONDARY outcome

Timeframe: Baseline, Day 15, 29, 43, 57, 71, 85

Population: Participants in the pharmacodynamic (PD) analysis set from the arms "ACZ885 600 mg" and "Placebo to ACZ885" who had an available value for the outcome measure. The PD analysis set included all participants with available PD data and no protocol deviations with relevant impact on PD data. In alignment with the study protocol, data collected beyond Day 85 for KOOS function in daily living subscale is not part of this secondary outcome measure comparing the groups ACZ885 versus Placebo to ACZ885.

The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales. One of those is the KOOS Function in Daily Living (ADL) subscale consisting of 17 questions with a recall of 7days. Each question has 5 standardized answer options with a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale.

Outcome measures

Outcome measures
Measure	Placebo to ACZ885+LNA043 40 mg n=8 Participants Placebo to ACZ885 single dose intra-articular (i.a) followed by LNA043 40 mg administrated i.a every four weeks, three times.	Placebo to ACZ885 n=8 Participants Placebo to ACZ885 single dose intra-articular.	ACZ885 600 mg ACZ885 600 mg single dose intra-articular.
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living (ADL) Subscale Over Time (ACZ885 Versus Placebo to ACZ885) Day 15	11.9 score on scale Standard Deviation 23.87	18.4 score on scale Standard Deviation 18.35	—
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living (ADL) Subscale Over Time (ACZ885 Versus Placebo to ACZ885) Day 29	14.3 score on scale Standard Deviation 24.74	25.7 score on scale Standard Deviation 20.72	—
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living (ADL) Subscale Over Time (ACZ885 Versus Placebo to ACZ885) Day 43	9.7 score on scale Standard Deviation 17.04	26.1 score on scale Standard Deviation 19.79	—
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living (ADL) Subscale Over Time (ACZ885 Versus Placebo to ACZ885) Day 57	16.7 score on scale Standard Deviation 28.06	31.8 score on scale Standard Deviation 21.99	—
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living (ADL) Subscale Over Time (ACZ885 Versus Placebo to ACZ885) Day 71	16.8 score on scale Standard Deviation 22.30	28.7 score on scale Standard Deviation 19.40	—
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Function in Daily Living (ADL) Subscale Over Time (ACZ885 Versus Placebo to ACZ885) Day 85	14.7 score on scale Standard Deviation 23.05	23.7 score on scale Standard Deviation 19.26	—

SECONDARY outcome

Timeframe: Baseline, Day 15, 29, 43, 57, 71, 85, 197 and 365

Population: Participants in the pharmacodynamic (PD) analysis set from the arms "Placebo to ACZ885+LNA043 40 mg", "ACZ885 600 mg + LNA043 40 mg" and "ACZ885 600 mg" who had an available value for the outcome measure. The PD analysis set included all participants with available PD data and no protocol deviations with relevant impact on PD data.

The KOOS questionnaire is a commonly used instrument to assess the patient's perception about their knee and associated problems. The original KOOS consists of 5 subscales. One of those is the KOOS Function in Daily Living (ADL) subscale consisting of 17 questions with a recall of 7days. Each question has 5 standardized answer options with a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale.