Change from Visit 2 (Baseline) to Visit 8 (Week 26) in normalised WOMAC pain score. The WOMAC responses are scored using an 11-point NRS where 0=none and 10=extreme. There are 5 questions in the WOMAC pain scale which is summed up for the total WOMAC score, leading to a range of 0 to 50. The total WOMAC pain score has been standardised to a scale with a range from 0 to 100 (where 100 is extreme pain):

- Normalised WOMAC pain score = Total WOMAC pain score multiplicated with 2.

Change from Visit 2 (Baseline) to Visit 8 (Week 26) in normalised WOMAC difficulty score. The WOMAC responses are scored using an 11-point NRS where 0=none and 10=extreme. There are 17 questions in the WOMAC difficulty scale which is summed up for the total WOMAC difficulty score, leading to a range of 0 to 170. The total WOMAC difficulty score has been standardised to a scale with a range from 0 to 100 (where 100 is extreme pain):

- Normalised WOMAC difficulty score = Total WOMAC difficulty score divided with 1.7

Change from Visit 2 (Baseline) to Visit 8 (Week 26) in normalised WOMAC stiffness score. The WOMAC responses are scored using an 11-point NRS where 0=none and 10=extreme. There are 2 questions in the WOMAC stiffness scale which is summed up for the total WOMAC stiffness score, leading to a range of 0 to 20. The total WOMAC stiffness score has been standardised to a scale with a range from 0 to 100 (where 100 is extreme pain):

- Normalised WOMAC stiffness score = Total WOMAC stiffness score multiplicated with 5

Change from Visit 2 (baseline) to Visit 8 (week 26) in serum CTX-I, a biomarker for bone resorption.

Change from Visit 2 (baseline) to Visit 8 (week 26) in creatinine corrected urine CTX-II, a biomarker for cartilage degradation.

Placebo manufactured to mimic MIV-711 capsule administered orally once daily for a total of 26 weeks

Total of all reporting groups

Placebo, manufactured to mimic MIV-711 capsule, administered orally once daily for a total of 26 weeks

Change from Visit 2 (Baseline) to Visit 8 (Week 26) in MRI (Magnetic Resonance Imaging;) bone area of the target knee in mm^2.

As there were discontinuations in the study, not all patients in the mITT population had an MRI assessment at week 26. In addition, there were patients with non valid MRIs. The analysis population is therefore smaller than the Participant Flow.

Change from Visit 2 (baseline) to Visit 8 (week 26) in MRI cartilage thickness in the Central Medial Femur Region of the target knee in mm.

As there were discontinuations in the study, not all patients in the mITT population had an MRI assessment at week 26. In addition, there were patients with non valid MRIs. The analysis population is therefore smaller than the Participant Flow.

Change from Visit 2 (Baseline) to Visit 8 (Week 26) in normalised WOMAC pain score. The WOMAC responses are scored using an 11-point NRS where 0=none and 10=extreme. There are 5 questions in the WOMAC pain scale which is summed up for the total WOMAC score, leading to a range of 0 to 50. The total WOMAC pain score has been standardised to a scale with a range from 0 to 100 (where 100 is extreme pain):

- Normalised WOMAC pain score = Total WOMAC pain score multiplicated with 2.

As there were discontinuations in the study, not all patients in the mITT population had an assessment at week 26. The analysis population is therefore equal to the number of patients completing the study for this outcome measure.

Change from Visit 2 (Baseline) to Visit 8 (Week 26) in normalised WOMAC difficulty score. The WOMAC responses are scored using an 11-point NRS where 0=none and 10=extreme. There are 17 questions in the WOMAC difficulty scale which is summed up for the total WOMAC difficulty score, leading to a range of 0 to 170. The total WOMAC difficulty score has been standardised to a scale with a range from 0 to 100 (where 100 is extreme pain):

- Normalised WOMAC difficulty score = Total WOMAC difficulty score divided with 1.7

As there were discontinuations in the study, not all patients in the mITT population had an assessment at week 26. The analysis population is therefore equal to the number of patients completing the study for this outcome measure.

Change from Visit 2 (Baseline) to Visit 8 (Week 26) in normalised WOMAC stiffness score. The WOMAC responses are scored using an 11-point NRS where 0=none and 10=extreme. There are 2 questions in the WOMAC stiffness scale which is summed up for the total WOMAC stiffness score, leading to a range of 0 to 20. The total WOMAC stiffness score has been standardised to a scale with a range from 0 to 100 (where 100 is extreme pain):

- Normalised WOMAC stiffness score = Total WOMAC stiffness score multiplicated with 5

As there were discontinuations in the study, not all patients in the mITT population had an assessment at week 26. The analysis population is therefore equal to the number of patients completing the study for this outcome measure.

Change from Visit 2 (baseline) to Visit 8 (week 26) in serum CTX-I, a biomarker for bone resorption.

As there were discontinuations in the study, not all patients in the mITT population had an assessment at week 26. In addition, there was one missing sample for serum CTX-I. The analysis population is therefore smaller than in the Participant Flow.

Change from Visit 2 (baseline) to Visit 8 (week 26) in creatinine corrected urine CTX-II, a biomarker for cartilage degradation.

As there were discontinuations in the study, not all patients in the mITT population had an assessment at week 26. In addition, there was two missing samples for urine CTX-II. The analysis population is therefore smaller than in the Participant Flow.

MIV-711 200 mg administered orally once daily for a total of 26 weeks

Placebo, manufactured to mimic MIV-711 capsule, administered orally once daily for a total of 26 weeks

A linear mixed model based on the mITT population was used. The model included fixed factors for treatment, time (measured in weeks), the interaction for treatment-by-time, baseline analgesic user (Yes/No), and random effect for clinical site. Baseline knee joint MRI bone area was included as a covariate for adjustment.

An unstructured covariance matrix was used to model the covariance pattern in the mixed effects model.

p-values reported are unadjusted p-values for tests of significance for the upper one-tailed alternative hypothesis Ha: bone area increase is lower in the active treatment arm compared to placebo.

One model is fit for all comparison groups (MIV-711 200 mg, MIV-711 100 mg and placebo). This analysis reports the contrast that compares 100 mg versus placebo with respect to mean change from baseline in knee joint MRI bone area at Week 26.

A linear mixed model based on the mITT population was used. The model included fixed factors for treatment, time (measured in weeks), the interaction for treatment-by-time, baseline analgesic user (Yes/No), and random effect for clinical site. Baseline MRI of cartilage thickness was included as a covariate for adjustment.

An unstructured covariance matrix was used to model the covariance pattern in the mixed effects model.

p-values reported are unadjusted p-values for tests of significance for the upper one-tailed alternative hypothesis Ha: MRI of cartilage thinning (Femur Region) is lower in the active treatment arm compared to placebo.

One model is fit for all comparison groups (MIV-711 200 mg, MIV-711 100 mg and placebo). This analysis reports the contrast that compares 100 mg versus placebo with respect to mean change from baseline in MRI of cartilage thickness (Femur Region) at Week 26.

A linear mixed model based on the mITT population was used. The model included fixed factors for treatment, time (measured in weeks), the interaction for treatment-by-time, baseline analgesic (Yes/No) and random effect for clinical site. Baseline WOMAC Pain score was included as a covariate for adjustment.

An unstructured covariance matrix was used to model the covariance pattern in the mixed effects model.

p-values reported are unadjusted p-values for tests of significance for the lower one-tailed alternative hypothesis Ha: Reduction in WOMAC Pain score is higher in the active treatment arm compared to placebo.

One model is fit for all comparison groups (MIV-711 200 mg, MIV-711 100 mg and placebo). This analysis reports the contrast that compares 100 mg versus placebo with respect to mean change from baseline in WOMAC Pain score at Week 26.

A linear mixed model based on the mITT population was used. The model included fixed factors for treatment, time (measured in weeks), the interaction for treatment-by-time, baseline analgesic (Yes/No) and random effect for clinical site. Baseline WOMAC difficulty score was included as a covariate for adjustment.

An unstructured covariance matrix was used to model the covariance pattern in the mixed effects model.

p-values reported are unadjusted p-values for tests of significance for the lower one-tailed alternative hypothesis Ha: Reduction in WOMAC Difficulty score is higher in the active treatment arm compared to placebo.

One model is fit for all comparison groups (MIV-711 200 mg, MIV-711 100 mg and placebo). This analysis reports the contrast that compares 100 mg versus placebo with respect to mean change from baseline in WOMAC difficulty score at Week 26.

A linear mixed model based on the mITT population was used. The model included fixed factors for treatment, time (measured in weeks), the interaction for treatment-by-time, baseline analgesic user (Yes/No), and random effect for clinical site. Baseline WOMAC stiffness score was included as a covariate for adjustment.

An unstructured covariance matrix was used to model the covariance pattern in the mixed effects model.

p-values reported are unadjusted p-values for tests of significance for the lower one-tailed alternative hypothesis Ha: Reduction in WOMAC Stiffness score is higher in the active treatment arm compared to placebo.

One model is fit for all comparison groups (MIV-711 200 mg, MIV-711 100 mg and placebo). This analysis reports the contrast that compares 100 mg versus placebo with respect to mean change from baseline in WOMAC stiffness score at Week 26.

A linear mixed model based on the mITT population was used. The model included fixed factors for treatment, time (measured in weeks), the interaction for treatment-by-time, baseline analgesic user (Yes/No), and random effect for clinical site. Baseline CTX-I score was included as a covariate for adjustment.

An unstructured covariance matrix was used to model the covariance pattern in the mixed effects model.

p-values reported are unadjusted p-values for tests of significance for the upper one-tailed alternative hypothesis Ha: CTX-I score is lower in the active treatment arm compared to placebo.

One model is fit for all comparison groups (MIV-711 200 mg, MIV-711 100 mg and placebo). This analysis reports the contrast that compares 100 mg versus placebo with respect to mean change from baseline in CTX-I score at Week 26.

A linear mixed model based on the mITT population was used. The model included fixed factors for treatment, time (measured in weeks), the interaction for treatment-by- time, baseline analgesic user (Yes/No), and random effect for clinical site. Baseline CTX-II score was included as a covariate for adjustment.

An unstructured covariance matrix was used to model the covariance pattern in the mixed effects model.

p-values reported are unadjusted p-values for tests of significance for the upper one-tailed alternative hypothesis Ha: CTX-II score is lower in the active treatment arm compared to placebo.

One model is fit for all comparison groups (MIV-711 200 mg, MIV-711 100 mg and placebo). This analysis reports the contrast that compares 100 mg versus placebo with respect to mean change from baseline in CTX-II score at Week 26.