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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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 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.

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.

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.

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.

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.

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.

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.