Osteoarthritis
Conditions
Brief summary
This study is a phase 2, 52-week international, multi-regional, multi-center, randomized, double-blind, placebo-controlled dose-ranging study for the treatment of osteoarthritis.
Interventions
DRUGGLPG1972
Film-coated tablets of GLPG1972 for oral use.
DRUGPlacebo
Film-coated tablets of matching placebo for oral use.
Sponsors
Institut de Recherches Internationales Servier
Galapagos NV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male participants or female participants of non-childbearing potential and not breastfeeding. * Body weight \> 40 kg, body mass index (BMI) \< 40 kg/m\^2. * Diagnosed for knee osteoarthritis based on clinical and radiological criteria of the American College of Rheumatology. * History of knee pain for at least 6 months and on the majority of days (\> 50%) during the preceding month. * Symptom severity defined by a pain ≥ 40 mm and ≤ 90 mm on visual analogue scale (VAS, 100 mm) at screening and inclusion visits. * Documented need for symptomatic as needed-treatment for osteoarthritis (OA) in the target knee with systemic non-steroidal anti-inflammatory drugs (NSAIDs) and/or other analgesics
Exclusion criteria
* Severe clinical knee malalignment according to the investigator. * Knee prosthesis already implanted (\< 1 year) or not well-tolerated (contralateral side). * Knee prosthesis already foreseen within the study period (whichever side). * Hip prosthesis recently implanted (\< 1 year) or foreseen within the study period (whichever side). * Previous osteotomy on the inferior limbs (whichever side). * Surgical operation on the target knee within the 12 months prior to the screening visit or planned during the study. * Diagnostic arthroscopy of the target knee within the 6 months prior to the screening visit or planned during the study. * Other pathologies affecting the target knee. * Any contraindication to magnetic resonance imaging (MRI) including the inability to undergo a knee MRI exam because of inability to fit in the scanner or knee coil.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Cartilage Thickness of the cMTFC as Assessed by qMRI on the Target Knee to Week 52 | Baseline, Week 52 | Reduction in cartilage loss was assessed by cartilage thickness as measured in the medial cMTFC of the target knee using qMRI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Baseline, Week 52 | Western Ontario and McMaster Universities Osteoarthritis Index is a questionnaire designed to assess health status and health outcomes in participants with OA of the knee. The questionnaire contains 24 questions targeting areas of pain, stiffness, and physical function. Pain subscale includes 5 items rated on a Likert scale of 0 (none) to 4 (extreme) with a total range of 0-20 with higher scores indicating worse symptoms and function. Stiffness subscale includes 2 items rated on a Likert scale of 0 (none) to 4 (extreme) with a total range of 0-8 with higher scores indicating worse symptoms and function. Physical function subscale includes 17 items rated on a Likert scale of 0 (none) to 4 (extreme) with a total range of 0-68 with higher scores indicating worse symptoms and function. The total score is the sum of all subscales (range: 0 to 96) with higher scores indicating worse symptoms and function. |
| Change From Baseline in Pain Assessment in the Target Knee as Measured by Visual Analog Scale (VAS) to Week 52 | Baseline, Week 52 | The participant was asked how would you rate the pain felt in the selected knee within the last 48 hours?. The participants rated the pain by marking the level of pain on a 100-mm VAS, with 0 being no pain and 100 being extreme pain. Higher score indicated higher pain intensity. |
| Change From Baseline in Patient Global Assessment (PGA) of Disease Activity as Measured by VAS to Week 52 | Baseline, Week 52 | The participant was asked Considering all the ways in which your knee osteoarthritis affects you, please rate on this 100 mm scale how well you are doing today. The participants rated the disease activity by marking on a 100-mm VAS, with 0 being no pain and 100 being extreme pain. Higher score indicated higher disease activity. |
| Number of Participants Who Were Responders Based on the Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Criteria | Week 52 | OMERACT-OARSI criteria involves improvement based on WOMAC pain and function subscales and PGA. The responders according to OMERACT-OARSI criteria were participants who had: * A high improvement in pain or in function ≥ 50% and absolute change ≥ 20, OR * Improvement in at least 2 of the 3 following: * Pain ≥ 20% and absolute change ≥ 10 * Function ≥ 20% and absolute change ≥ 10 * Patient's global assessment ≥ 20% and absolute change ≥ 10. WOMAC pain subscale score: range of 0 to 20, higher scores indicating more pain, WOMAC physical function subscale score: range of 0 to 68, higher scores indicating worse physical function), PGA: The participant was asked Considering all the ways in which your knee osteoarthritis affects you, please rate on this 100 mm scale how well you are doing today. The participants rated disease activity by marking on a 100-mm VAS, with 0 being no pain and 100 being extreme pain. Higher score indicated higher disease activity. |
| Change From Baseline in Cartilage Thickness of the Total Tibiofemoral Compartment (tTFC) of the Target Knee by qMRI to Week 52 | Baseline, Week 52 | Reduction of cartilage loss was measured by cartilage thickness of the tTFC of the target knee using qMRI. |
| Number of Participants Who Were Osteoarthritis (OA) Structural Progressors Based on Cartilage Thickness in the cMTFC Assessed by qMRI on the Target Knee | Week 52 | A structural progressor was defined as a participant who had an 8% cartilage loss in cMTFC. Number of participants who met the criteria of structural progressor at Week 52 are provided. |
| Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 52 | Baseline, Week 52 | — |
| Change From Baseline in Joint Space Width (JSW) of the Target Knee to Week 52 | Baseline, Week 52 | The JSW is the space measured between the 2 bones in the knee joint and this is assessed by x-ray. |
| Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Baseline up to Week 52 | Systemic analgesics included anti-inflammatory and anti-rheumatic products; analgesics; anti-diarrheals, intestinal, anti-inflammatory/anti-infective agents; and drugs for functional gastrointestinal disorders. |
| Plasma Concentrations of GLPG1972 | Pre-dose at Weeks 4, 12, and 52; Pre-dose and one post-dose sample (2-4 hours interval) at Week 28; one post dose sample (interval 4-8 hours) at Week 40 | — |
| Number of Participants With Treatment-emergent Adverse Event (TEAE) | Baseline up to 2-weeks after last dose of IMP (up to Week 54) | TEAEs were defined as all adverse events (AEs) that occurred: * between first IMP intake date (included) and last visit of participant, or * before first IMP intake date and that worsened (in terms of intensity) or became serious according to investigator opinion between first IMP intake date (included) and last visit of participant. Number of participants with at least 1 TEAE (serious or non-serious) are reported. |
| Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 28 | Baseline, Week 28 | — |
Countries
United States
Participant flow
Recruitment details
The first participant was screened on 14 August 2018. The last study visit occurred on 14 July 2020. Due to the exceptional circumstances in relation to the COVID-19 pandemic, the Sponsor decided in accordance with competent regulatory authorities' guidelines to implement some precautionary measures in order to mitigate the risk of infection.
Pre-assignment details
A total of 3319 participants were screened and 932 participants were randomized and 931 participants were treated.
Participants by arm
| Arm | Count |
|---|---|
| GLPG1972 75 mg Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks. | 234 |
| GLPG1972 150 mg Participants received 2 film-coated tablets of GLPG1972 75 mg (total dose 150 mg) and 2 GLPG1972 matching placebo tablets, orally once daily for 52 weeks. | 231 |
| GLPG1972 300 mg Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks. | 233 |
| Placebo Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks. | 234 |
| Total | 932 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 16 | 17 | 20 | 8 |
| Overall Study | Lost to Follow-up | 6 | 4 | 5 | 6 |
| Overall Study | Miscellaneous | 7 | 5 | 10 | 6 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 2 |
| Overall Study | Protocol Violation | 2 | 0 | 6 | 2 |
| Overall Study | Withdrawal by Subject | 12 | 14 | 14 | 10 |
Baseline characteristics
| Characteristic | GLPG1972 75 mg | GLPG1972 150 mg | GLPG1972 300 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 62.9 Years STANDARD_DEVIATION 7.5 | 63.2 Years STANDARD_DEVIATION 7.2 | 62.1 Years STANDARD_DEVIATION 7.4 | 63.3 Years STANDARD_DEVIATION 7.1 | 62.9 Years STANDARD_DEVIATION 7.3 |
| Cartilage Thickness of the Central Medial Tibiofemoral Compartment (cMTFC) of the Target Knee | 3.25316 mm STANDARD_DEVIATION 0.75857 | 3.23101 mm STANDARD_DEVIATION 0.75531 | 3.33075 mm STANDARD_DEVIATION 0.79839 | 3.18554 mm STANDARD_DEVIATION 0.81513 | 3.24996 mm STANDARD_DEVIATION 0.78289 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 52 Participants | 52 Participants | 36 Participants | 53 Participants | 193 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 182 Participants | 179 Participants | 197 Participants | 181 Participants | 739 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 31 Participants | 28 Participants | 30 Participants | 32 Participants | 121 Participants |
| Race (NIH/OMB) Black or African American | 27 Participants | 19 Participants | 25 Participants | 25 Participants | 96 Participants |
| Race (NIH/OMB) More than one race | 8 Participants | 6 Participants | 8 Participants | 6 Participants | 28 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 167 Participants | 177 Participants | 168 Participants | 171 Participants | 683 Participants |
| Sex: Female, Male Female | 164 Participants | 165 Participants | 154 Participants | 163 Participants | 646 Participants |
| Sex: Female, Male Male | 70 Participants | 66 Participants | 79 Participants | 71 Participants | 286 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 234 | 1 / 231 | 0 / 232 | 0 / 234 |
| other Total, other adverse events | 114 / 234 | 124 / 231 | 105 / 232 | 130 / 234 |
| serious Total, serious adverse events | 17 / 234 | 17 / 231 | 18 / 232 | 18 / 234 |
Outcome results
Primary
Change From Baseline in Cartilage Thickness of the cMTFC as Assessed by qMRI on the Target Knee to Week 52
Reduction in cartilage loss was assessed by cartilage thickness as measured in the medial cMTFC of the target knee using qMRI.
Time frame: Baseline, Week 52
Population: Analysis was based on the mRS. Overall number of participants analyzed included participants with available data of cartilage thickness in the cMTFC at baseline and Week 52.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GLPG1972 75 mg | Change From Baseline in Cartilage Thickness of the cMTFC as Assessed by qMRI on the Target Knee to Week 52 | -0.06791 mm | Standard Deviation 0.20169 |
| GLPG1972 150 mg | Change From Baseline in Cartilage Thickness of the cMTFC as Assessed by qMRI on the Target Knee to Week 52 | -0.09693 mm | Standard Deviation 0.26839 |
| GLPG1972 300 mg | Change From Baseline in Cartilage Thickness of the cMTFC as Assessed by qMRI on the Target Knee to Week 52 | -0.08545 mm | Standard Deviation 0.21697 |
| Placebo | Change From Baseline in Cartilage Thickness of the cMTFC as Assessed by qMRI on the Target Knee to Week 52 | -0.11562 mm | Standard Deviation 0.27275 |
Comparison: Estimate (Standard Error) of adjusted difference from baseline to last post baseline value between treatment groups means: GLPG1972 dose minus placebo using mixed-effects model for repeated measures (MMRM) including fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as continuous, fixed covariates of baseline and time-by-baseline interaction preceded by multiple imputation step for participants without post baseline valuep-value: 0.16595% CI: [-0.00317, 0.09345]Mixed Models Analysis
Comparison: Estimate (Standard Error) of adjusted difference from baseline to last post baseline value between treatment groups means: GLPG1972 dose minus placebo using MMRM including fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as continuous, fixed covariates of baseline and time-by-baseline interaction preceded by multiple imputation step for participants without post baseline value.p-value: 0.93995% CI: [-0.03868, 0.06267]Mixed Models Analysis
Comparison: Estimate (Standard Error) of adjusted difference from baseline to last post baseline value between treatment groups means: GLPG1972 dose minus placebo using MMRM including fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as continuous, fixed covariates of baseline and time-by-baseline interaction preceded by multiple imputation step for participants without post baseline value.p-value: 0.68295% CI: [-0.02641, 0.073]Mixed Models Analysis
Secondary
Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 28
Time frame: Baseline, Week 28
Population: Analysis was based on mRS. Overall number of participants analyzed included participants with available data of bone area of the medial femoral condyle surface of the target knee at baseline. Number of participants analyzed for change from baseline to Week 28 included participants with available data of bone area of the medial femoral condyle surface of the target knee at baseline and Week 28.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GLPG1972 75 mg | Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 28 | Baseline | 2343.32026 mm^2 | Standard Deviation 371.23246 |
| GLPG1972 75 mg | Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 28 | Change from baseline to Week 28 | 8.21893 mm^2 | Standard Deviation 31.81812 |
| GLPG1972 150 mg | Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 28 | Change from baseline to Week 28 | 11.11178 mm^2 | Standard Deviation 33.14557 |
| GLPG1972 150 mg | Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 28 | Baseline | 2346.17547 mm^2 | Standard Deviation 373.46086 |
| GLPG1972 300 mg | Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 28 | Baseline | 2354.77368 mm^2 | Standard Deviation 385.91599 |
| GLPG1972 300 mg | Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 28 | Change from baseline to Week 28 | 7.63991 mm^2 | Standard Deviation 33.60899 |
| Placebo | Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 28 | Baseline | 2333.67525 mm^2 | Standard Deviation 362.46041 |
| Placebo | Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 28 | Change from baseline to Week 28 | 11.43549 mm^2 | Standard Deviation 29.6081 |
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: Placebo minus GLPG1972 dose regimen using an analysis of covariance (ANCOVA) including the factors treatment and region with baseline as covariate and no interaction, after a Multiple Imputation for missing data.p-value: 0.62795% CI: [-3.02464, 9.27252]ANCOVA
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: Placebo minus GLPG1972 dose regimen using an ANCOVA including the factors treatment and region with baseline as covariate and no interaction, after a Multiple Imputation for missing data.p-value: 0.99895% CI: [-5.82659, 6.76343]ANCOVA
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: Placebo minus GLPG1972 dose regimen using an ANCOVA including the factors treatment and region with baseline as covariate and no interaction, after a Multiple Imputation for missing data.p-value: 0.44995% CI: [-2.30536, 10.54049]ANCOVA
Secondary
Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 52
Time frame: Baseline, Week 52
Population: Analysis was based on mRS. Overall number of participants analyzed included participants with available data of bone area of the medial femoral condyle surface of the target knee at baseline. Number of participants analyzed for change from baseline to Week 52 included participants with available data of bone area of the medial femoral condyle surface of the target knee at baseline and Week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GLPG1972 75 mg | Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 52 | Baseline | 2343.32026 mm^2 | Standard Deviation 371.23246 |
| GLPG1972 75 mg | Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 52 | Change from baseline to Week 52 | 15.45592 mm^2 | Standard Deviation 31.22629 |
| GLPG1972 150 mg | Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 52 | Change from baseline to Week 52 | 22.06801 mm^2 | Standard Deviation 42.85848 |
| GLPG1972 150 mg | Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 52 | Baseline | 2346.17547 mm^2 | Standard Deviation 373.46086 |
| GLPG1972 300 mg | Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 52 | Baseline | 2354.77368 mm^2 | Standard Deviation 385.91599 |
| GLPG1972 300 mg | Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 52 | Change from baseline to Week 52 | 20.78279 mm^2 | Standard Deviation 34.96462 |
| Placebo | Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 52 | Baseline | 2333.67525 mm^2 | Standard Deviation 362.46041 |
| Placebo | Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 52 | Change from baseline to Week 52 | 18.08990 mm^2 | Standard Deviation 35.9365 |
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose regimen using a MMRM including the fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as the continuous, fixed covariates of baseline and time-by-baseline interaction preceded by a Multiple Imputation step for participants without post-baseline measurement.p-value: 0.78995% CI: [-4.51643, 10.21205]Mixed Models Analysis
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose regimen using a MMRM including the fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as the continuous, fixed covariates of baseline and time-by-baseline interaction preceded by a Multiple Imputation step for participants without post-baseline measurement.p-value: 0.66195% CI: [-11.19071, 3.89553]Mixed Models Analysis
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose regimen using a MMRM including the fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as the continuous, fixed covariates of baseline and time-by-baseline interaction preceded by a Multiple Imputation step for participants without post-baseline measurement.p-value: 0.84395% CI: [-10.04053, 4.93701]Mixed Models Analysis
Secondary
Change From Baseline in Cartilage Thickness of the Total Tibiofemoral Compartment (tTFC) of the Target Knee by qMRI to Week 52
Reduction of cartilage loss was measured by cartilage thickness of the tTFC of the target knee using qMRI.
Time frame: Baseline, Week 52
Population: Analysis was based on mRS. Overall number of participants analyzed included participants with available data of cartilage thickness of the tTFC of the target knee at baseline. Number of participants analyzed for change from baseline to Week 52 included participants with available data of cartilage thickness of the tTFC of the target knee at baseline and Week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GLPG1972 75 mg | Change From Baseline in Cartilage Thickness of the Total Tibiofemoral Compartment (tTFC) of the Target Knee by qMRI to Week 52 | Baseline | 6.49218 mm | Standard Deviation 1.02749 |
| GLPG1972 75 mg | Change From Baseline in Cartilage Thickness of the Total Tibiofemoral Compartment (tTFC) of the Target Knee by qMRI to Week 52 | Change from baseline to Week 52 | -0.03572 mm | Standard Deviation 0.17673 |
| GLPG1972 150 mg | Change From Baseline in Cartilage Thickness of the Total Tibiofemoral Compartment (tTFC) of the Target Knee by qMRI to Week 52 | Change from baseline to Week 52 | -0.02401 mm | Standard Deviation 0.20766 |
| GLPG1972 150 mg | Change From Baseline in Cartilage Thickness of the Total Tibiofemoral Compartment (tTFC) of the Target Knee by qMRI to Week 52 | Baseline | 6.57424 mm | Standard Deviation 1.02706 |
| GLPG1972 300 mg | Change From Baseline in Cartilage Thickness of the Total Tibiofemoral Compartment (tTFC) of the Target Knee by qMRI to Week 52 | Baseline | 6.51256 mm | Standard Deviation 0.97704 |
| GLPG1972 300 mg | Change From Baseline in Cartilage Thickness of the Total Tibiofemoral Compartment (tTFC) of the Target Knee by qMRI to Week 52 | Change from baseline to Week 52 | -0.01678 mm | Standard Deviation 0.20934 |
| Placebo | Change From Baseline in Cartilage Thickness of the Total Tibiofemoral Compartment (tTFC) of the Target Knee by qMRI to Week 52 | Baseline | 6.45879 mm | Standard Deviation 1.01774 |
| Placebo | Change From Baseline in Cartilage Thickness of the Total Tibiofemoral Compartment (tTFC) of the Target Knee by qMRI to Week 52 | Change from baseline to Week 52 | -0.06447 mm | Standard Deviation 0.2348 |
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose regimen using a MMRM including the fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as the continuous, fixed covariates of baseline and time-by-baseline interaction preceded by a Multiple Imputation step for participants without post-baseline measurement.p-value: 0.19395% CI: [-0.00448, 0.08005]Mixed Models Analysis
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose regimen using a MMRM including the fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as the continuous, fixed covariates of baseline and time-by-baseline interaction preceded by a Multiple Imputation step for participants without post-baseline measurement.p-value: 0.25695% CI: [-0.00801, 0.07962]Mixed Models Analysis
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose regimen using a MMRM including the fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as the continuous, fixed covariates of baseline and time-by-baseline interaction preceded by a Multiple Imputation step for participants without post-baseline measurement.p-value: 0.20195% CI: [-0.00514, 0.08281]Mixed Models Analysis
Secondary
Change From Baseline in Joint Space Width (JSW) of the Target Knee to Week 52
The JSW is the space measured between the 2 bones in the knee joint and this is assessed by x-ray.
Time frame: Baseline, Week 52
Population: Analysis was based on mRS. Overall number of participants analyzed included participants with available data of JSW at baseline. Number of participants analyzed for change from baseline to Week 52 included participants with available data of JSW at baseline and Week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GLPG1972 75 mg | Change From Baseline in Joint Space Width (JSW) of the Target Knee to Week 52 | Baseline | 2.504 mm | Standard Deviation 0.779 |
| GLPG1972 75 mg | Change From Baseline in Joint Space Width (JSW) of the Target Knee to Week 52 | Change from baseline to Week 52 | -0.087 mm | Standard Deviation 0.397 |
| GLPG1972 150 mg | Change From Baseline in Joint Space Width (JSW) of the Target Knee to Week 52 | Change from baseline to Week 52 | -0.167 mm | Standard Deviation 0.506 |
| GLPG1972 150 mg | Change From Baseline in Joint Space Width (JSW) of the Target Knee to Week 52 | Baseline | 2.500 mm | Standard Deviation 0.783 |
| GLPG1972 300 mg | Change From Baseline in Joint Space Width (JSW) of the Target Knee to Week 52 | Baseline | 2.577 mm | Standard Deviation 0.84 |
| GLPG1972 300 mg | Change From Baseline in Joint Space Width (JSW) of the Target Knee to Week 52 | Change from baseline to Week 52 | -0.113 mm | Standard Deviation 0.464 |
| Placebo | Change From Baseline in Joint Space Width (JSW) of the Target Knee to Week 52 | Baseline | 2.483 mm | Standard Deviation 0.859 |
| Placebo | Change From Baseline in Joint Space Width (JSW) of the Target Knee to Week 52 | Change from baseline to Week 52 | -0.174 mm | Standard Deviation 0.47 |
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: GLPG1972 dose regimen minus placebo using an ANCOVA including the factors treatment and region with baseline as covariate and no interaction, after a Multiple Imputation for missing data.p-value: 0.14195% CI: [-0.0028, 0.1929]ANCOVA
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: GLPG1972 dose regimen minus placebo using an ANCOVA including the factors treatment and region with baseline as covariate and no interaction, after a Multiple Imputation for missing data.p-value: 0.98195% CI: [-0.0861, 0.1177]ANCOVA
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: GLPG1972 dose regimen minus placebo using an ANCOVA including the factors treatment and region with baseline as covariate and no interaction, after a Multiple Imputation for missing data.p-value: 0.34995% CI: [-0.0286, 0.1792]ANCOVA
Secondary
Change From Baseline in Pain Assessment in the Target Knee as Measured by Visual Analog Scale (VAS) to Week 52
The participant was asked how would you rate the pain felt in the selected knee within the last 48 hours?. The participants rated the pain by marking the level of pain on a 100-mm VAS, with 0 being no pain and 100 being extreme pain. Higher score indicated higher pain intensity.
Time frame: Baseline, Week 52
Population: Analysis was based on mRS. Overall number of participants analyzed included participants with available data of VAS at baseline. Number of participants analyzed for change from baseline to Week 52 included participants with available data of VAS at baseline and Week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GLPG1972 75 mg | Change From Baseline in Pain Assessment in the Target Knee as Measured by Visual Analog Scale (VAS) to Week 52 | Baseline | 63.3 mm | Standard Deviation 11.4 |
| GLPG1972 75 mg | Change From Baseline in Pain Assessment in the Target Knee as Measured by Visual Analog Scale (VAS) to Week 52 | Change from baseline to Week 52 | -27.2 mm | Standard Deviation 24.3 |
| GLPG1972 150 mg | Change From Baseline in Pain Assessment in the Target Knee as Measured by Visual Analog Scale (VAS) to Week 52 | Change from baseline to Week 52 | -25.6 mm | Standard Deviation 26.9 |
| GLPG1972 150 mg | Change From Baseline in Pain Assessment in the Target Knee as Measured by Visual Analog Scale (VAS) to Week 52 | Baseline | 63.8 mm | Standard Deviation 11.5 |
| GLPG1972 300 mg | Change From Baseline in Pain Assessment in the Target Knee as Measured by Visual Analog Scale (VAS) to Week 52 | Baseline | 63.3 mm | Standard Deviation 12.1 |
| GLPG1972 300 mg | Change From Baseline in Pain Assessment in the Target Knee as Measured by Visual Analog Scale (VAS) to Week 52 | Change from baseline to Week 52 | -28.2 mm | Standard Deviation 27.1 |
| Placebo | Change From Baseline in Pain Assessment in the Target Knee as Measured by Visual Analog Scale (VAS) to Week 52 | Baseline | 63.5 mm | Standard Deviation 11 |
| Placebo | Change From Baseline in Pain Assessment in the Target Knee as Measured by Visual Analog Scale (VAS) to Week 52 | Change from baseline to Week 52 | -28.9 mm | Standard Deviation 25 |
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose regimen using a MMRM including the fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as the continuous, fixed covariates of baseline and time-by-baseline interaction preceded by a Multiple Imputation step for participants without post-baseline measurement.p-value: 0.70595% CI: [-7.1, 2.7]Mixed Models Analysis
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose regimen using a MMRM including the fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as the continuous, fixed covariates of baseline and time-by-baseline interaction preceded by a Multiple Imputation step for participants without post-baseline measurement.p-value: 0.24395% CI: [-9, 0.8]Mixed Models Analysis
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose regimen using a MMRM including the fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as the continuous, fixed covariates of baseline and time-by-baseline interaction preceded by a Multiple Imputation step for participants without post-baseline measurement.p-value: 0.94995% CI: [-6.1, 3.9]Mixed Models Analysis
Secondary
Change From Baseline in Patient Global Assessment (PGA) of Disease Activity as Measured by VAS to Week 52
The participant was asked Considering all the ways in which your knee osteoarthritis affects you, please rate on this 100 mm scale how well you are doing today. The participants rated the disease activity by marking on a 100-mm VAS, with 0 being no pain and 100 being extreme pain. Higher score indicated higher disease activity.
Time frame: Baseline, Week 52
Population: Analysis was based on mRS. Overall number of participants analyzed included participants with available data of PGA score at baseline. Number of participants analyzed for change from baseline to Week 52 included participants with available data of PGA score at baseline and Week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GLPG1972 75 mg | Change From Baseline in Patient Global Assessment (PGA) of Disease Activity as Measured by VAS to Week 52 | Baseline | 47.1 mm | Standard Deviation 18.3 |
| GLPG1972 75 mg | Change From Baseline in Patient Global Assessment (PGA) of Disease Activity as Measured by VAS to Week 52 | Change from baseline to Week 52 | 19.4 mm | Standard Deviation 30 |
| GLPG1972 150 mg | Change From Baseline in Patient Global Assessment (PGA) of Disease Activity as Measured by VAS to Week 52 | Change from baseline to Week 52 | 14.3 mm | Standard Deviation 30.7 |
| GLPG1972 150 mg | Change From Baseline in Patient Global Assessment (PGA) of Disease Activity as Measured by VAS to Week 52 | Baseline | 47.9 mm | Standard Deviation 19 |
| GLPG1972 300 mg | Change From Baseline in Patient Global Assessment (PGA) of Disease Activity as Measured by VAS to Week 52 | Baseline | 49.4 mm | Standard Deviation 17.5 |
| GLPG1972 300 mg | Change From Baseline in Patient Global Assessment (PGA) of Disease Activity as Measured by VAS to Week 52 | Change from baseline to Week 52 | 14.1 mm | Standard Deviation 28.4 |
| Placebo | Change From Baseline in Patient Global Assessment (PGA) of Disease Activity as Measured by VAS to Week 52 | Baseline | 50.4 mm | Standard Deviation 19.2 |
| Placebo | Change From Baseline in Patient Global Assessment (PGA) of Disease Activity as Measured by VAS to Week 52 | Change from baseline to Week 52 | 14.0 mm | Standard Deviation 31.3 |
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: GLPG1972 dose regimen minus placebo using a MMRM including the fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as the continuous, fixed covariates of baseline and time-by-baseline interaction preceded by a Multiple Imputation step for participants without post-baseline measurement.p-value: 0.8995% CI: [-3.4, 6.3]Mixed Models Analysis
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: GLPG1972 dose regimen minus placebo using a MMRM including the fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as the continuous, fixed covariates of baseline and time-by-baseline interaction preceded by a Multiple Imputation step for participants without post-baseline measurement.p-value: 0.68295% CI: [-7.1, 2.6]Mixed Models Analysis
Comparison: Estimate (Standard Error) of the adjusted difference from baseline to last post baseline value between treatment groups means: GLPG1972 dose regimen minus placebo using a MMRM including the fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as the continuous, fixed covariates of baseline and time-by-baseline interaction preceded by a Multiple Imputation step for participants without post-baseline measurement.p-value: 195% CI: [-4.8, 5]Mixed Models Analysis
Secondary
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52
Western Ontario and McMaster Universities Osteoarthritis Index is a questionnaire designed to assess health status and health outcomes in participants with OA of the knee. The questionnaire contains 24 questions targeting areas of pain, stiffness, and physical function. Pain subscale includes 5 items rated on a Likert scale of 0 (none) to 4 (extreme) with a total range of 0-20 with higher scores indicating worse symptoms and function. Stiffness subscale includes 2 items rated on a Likert scale of 0 (none) to 4 (extreme) with a total range of 0-8 with higher scores indicating worse symptoms and function. Physical function subscale includes 17 items rated on a Likert scale of 0 (none) to 4 (extreme) with a total range of 0-68 with higher scores indicating worse symptoms and function. The total score is the sum of all subscales (range: 0 to 96) with higher scores indicating worse symptoms and function.
Time frame: Baseline, Week 52
Population: Analysis was based on mRS. Overall number of participants analyzed included participants with available data of WOMAC score at baseline. Number of participants analyzed for change from baseline to Week 52 included participants with available data of WOMAC score at baseline and Week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GLPG1972 75 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Total score: Baseline | 48.0 score on a scale | Standard Deviation 15.2 |
| GLPG1972 75 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Total score: Change from baseline to Week 52 | -16.3 score on a scale | Standard Deviation 17.7 |
| GLPG1972 75 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Pain subscore: Baseline | 10.2 score on a scale | Standard Deviation 3.2 |
| GLPG1972 75 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Pain subscore: Change from baseline to Week 52 | -3.9 score on a scale | Standard Deviation 4.1 |
| GLPG1972 75 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Physical function subscore: Baseline | 33.8 score on a scale | Standard Deviation 11.2 |
| GLPG1972 75 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Physical function subscore: Change from baseline to Week 52 | -11.2 score on a scale | Standard Deviation 12.7 |
| GLPG1972 75 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Stiffness subscore: Baseline | 4.0 score on a scale | Standard Deviation 1.7 |
| GLPG1972 75 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Stiffness subscore: Change from baseline to Week 52 | -1.2 score on a scale | Standard Deviation 2.1 |
| GLPG1972 150 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Physical function subscore: Change from baseline to Week 52 | -11.9 score on a scale | Standard Deviation 13 |
| GLPG1972 150 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Physical function subscore: Baseline | 34.3 score on a scale | Standard Deviation 11.2 |
| GLPG1972 150 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Total score: Change from baseline to Week 52 | -16.9 score on a scale | Standard Deviation 17.7 |
| GLPG1972 150 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Stiffness subscore: Change from baseline to Week 52 | -1.3 score on a scale | Standard Deviation 2 |
| GLPG1972 150 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Stiffness subscore: Baseline | 4.3 score on a scale | Standard Deviation 1.7 |
| GLPG1972 150 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Pain subscore: Change from baseline to Week 52 | -3.7 score on a scale | Standard Deviation 4 |
| GLPG1972 150 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Pain subscore: Baseline | 10.0 score on a scale | Standard Deviation 3.1 |
| GLPG1972 150 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Total score: Baseline | 48.7 score on a scale | Standard Deviation 15 |
| GLPG1972 300 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Stiffness subscore: Baseline | 4.2 score on a scale | Standard Deviation 1.6 |
| GLPG1972 300 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Pain subscore: Baseline | 9.8 score on a scale | Standard Deviation 3.1 |
| GLPG1972 300 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Pain subscore: Change from baseline to Week 52 | -3.7 score on a scale | Standard Deviation 4.2 |
| GLPG1972 300 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Physical function subscore: Baseline | 33.0 score on a scale | Standard Deviation 11.6 |
| GLPG1972 300 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Physical function subscore: Change from baseline to Week 52 | -10.9 score on a scale | Standard Deviation 14.7 |
| GLPG1972 300 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Stiffness subscore: Change from baseline to Week 52 | -1.4 score on a scale | Standard Deviation 2 |
| GLPG1972 300 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Total score: Baseline | 47.0 score on a scale | Standard Deviation 15.2 |
| GLPG1972 300 mg | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Total score: Change from baseline to Week 52 | -16.1 score on a scale | Standard Deviation 19.8 |
| Placebo | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Pain subscore: Baseline | 10.0 score on a scale | Standard Deviation 3.2 |
| Placebo | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Pain subscore: Change from baseline to Week 52 | -4.1 score on a scale | Standard Deviation 4.1 |
| Placebo | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Total score: Change from baseline to Week 52 | -18.4 score on a scale | Standard Deviation 18.9 |
| Placebo | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Total score: Baseline | 48.3 score on a scale | Standard Deviation 14.5 |
| Placebo | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Physical function subscore: Baseline | 34.1 score on a scale | Standard Deviation 10.7 |
| Placebo | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Stiffness subscore: Change from baseline to Week 52 | -1.5 score on a scale | Standard Deviation 2 |
| Placebo | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Stiffness subscore: Baseline | 4.2 score on a scale | Standard Deviation 1.6 |
| Placebo | Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52 | Physical function subscore: Change from baseline to Week 52 | -12.7 score on a scale | Standard Deviation 13.9 |
Comparison: Total score: Estimate (Standard Error) of adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose using MMRM including fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as continuous, fixed covariates of baseline and time-by-baseline interaction preceded by multiple imputation step for participants without post baseline value.p-value: 0.46795% CI: [-5.6, 1.3]Mixed Models Analysis
Comparison: Total score: Estimate (Standard Error) of adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose using MMRM including fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as continuous, fixed covariates of baseline and time-by-baseline interaction preceded by multiple imputation step for participants without post baseline value.p-value: 0.55795% CI: [-5.4, 1.5]Mixed Models Analysis
Comparison: Total score: Estimate (Standard Error) of adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose using MMRM including fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as continuous, fixed covariates of baseline and time-by-baseline interaction preceded by multiple imputation step for participants without post baseline value.p-value: 0.59395% CI: [-5.3, 1.6]Mixed Models Analysis
Comparison: Pain subscore: Estimate (Standard Error) of adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose using MMRM including fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as continuous, fixed covariates of baseline and time-by-baseline interaction preceded by multiple imputation step for participants without post baseline value.p-value: 0.77695% CI: [-1, 0.4]Mixed Models Analysis
Comparison: Pain subscore: Estimate (Standard Error) of adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose using MMRM including fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as continuous, fixed covariates of baseline and time-by-baseline interaction preceded by multiple imputation step for participants without post baseline value.p-value: 0.44695% CI: [-1.2, 0.3]Mixed Models Analysis
Comparison: Pain subscore: Estimate (Standard Error) of adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose using MMRM including fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as continuous, fixed covariates of baseline and time-by-baseline interaction preceded by multiple imputation step for participants without post baseline value.p-value: 0.64995% CI: [-1.1, 0.4]Mixed Models Analysis
Comparison: Physical function subscore: Estimate (Standard Error) of adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose using MMRM including fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as continuous, fixed covariates of baseline and time-by-baseline interaction preceded by multiple imputation step for participants without post baseline value.p-value: 0.45295% CI: [-4.1, 0.9]Mixed Models Analysis
Comparison: Physical Function subscore: Estimate (Standard Error) of adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose using MMRM including fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as continuous, fixed covariates of baseline and time-by-baseline interaction preceded by multiple imputation step for participants without post baseline value.p-value: 0.66595% CI: [-3.7, 1.3]Mixed Models Analysis
Comparison: Physical Function subscore: Estimate (Standard Error) of adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose using MMRM including fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as continuous, fixed covariates of baseline and time-by-baseline interaction preceded by multiple imputation step for participants without post baseline value.p-value: 0.59895% CI: [-3.9, 1.2]Mixed Models Analysis
Comparison: Stiffness subscore: Estimate (Standard Error) of adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose using MMRM including fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as continuous, fixed covariates of baseline and time-by-baseline interaction preceded by multiple imputation step for participants without post baseline value.p-value: 0.495% CI: [-0.6, 0.1]Mixed Models Analysis
Comparison: Stiffness subscore: Estimate (Standard Error) of adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose using MMRM including fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as continuous, fixed covariates of baseline and time-by-baseline interaction preceded by multiple imputation step for participants without post baseline value.p-value: 0.39395% CI: [-0.6, 0.1]Mixed Models Analysis
Comparison: Stiffness subscore: Estimate (Standard Error) of adjusted difference from baseline to last post baseline value between treatment groups means: placebo minus GLPG1972 dose using MMRM including fixed, categorical effects of treatment, region (Asia and Rest of the World), time and treatment-by-time interaction, as well as continuous, fixed covariates of baseline and time-by-baseline interaction preceded by multiple imputation step for participants without post baseline value.p-value: 0.85895% CI: [-0.5, 0.2]Mixed Models Analysis
Secondary
Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study
Systemic analgesics included anti-inflammatory and anti-rheumatic products; analgesics; anti-diarrheals, intestinal, anti-inflammatory/anti-infective agents; and drugs for functional gastrointestinal disorders.
Time frame: Baseline up to Week 52
Population: Analysis was based on mRS.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GLPG1972 75 mg | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Anti-diarrheals, intestinal anti-inflammatory/anti-infective agents | 0 Participants |
| GLPG1972 75 mg | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Anti-inflammatory and anti-rheumatic products | 173 Participants |
| GLPG1972 75 mg | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Drugs for functional gastrointestinal disorders | 1 Participants |
| GLPG1972 75 mg | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Analgesics | 127 Participants |
| GLPG1972 75 mg | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Participants with at least one treatment | 216 Participants |
| GLPG1972 150 mg | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Analgesics | 135 Participants |
| GLPG1972 150 mg | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Anti-diarrheals, intestinal anti-inflammatory/anti-infective agents | 1 Participants |
| GLPG1972 150 mg | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Drugs for functional gastrointestinal disorders | 0 Participants |
| GLPG1972 150 mg | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Anti-inflammatory and anti-rheumatic products | 167 Participants |
| GLPG1972 150 mg | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Participants with at least one treatment | 213 Participants |
| GLPG1972 300 mg | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Analgesics | 118 Participants |
| GLPG1972 300 mg | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Participants with at least one treatment | 211 Participants |
| GLPG1972 300 mg | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Anti-inflammatory and anti-rheumatic products | 180 Participants |
| GLPG1972 300 mg | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Anti-diarrheals, intestinal anti-inflammatory/anti-infective agents | 1 Participants |
| GLPG1972 300 mg | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Drugs for functional gastrointestinal disorders | 0 Participants |
| Placebo | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Anti-diarrheals, intestinal anti-inflammatory/anti-infective agents | 1 Participants |
| Placebo | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Anti-inflammatory and anti-rheumatic products | 178 Participants |
| Placebo | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Participants with at least one treatment | 212 Participants |
| Placebo | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Analgesics | 128 Participants |
| Placebo | Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study | Drugs for functional gastrointestinal disorders | 0 Participants |
Secondary
Number of Participants Who Were Osteoarthritis (OA) Structural Progressors Based on Cartilage Thickness in the cMTFC Assessed by qMRI on the Target Knee
A structural progressor was defined as a participant who had an 8% cartilage loss in cMTFC. Number of participants who met the criteria of structural progressor at Week 52 are provided.
Time frame: Week 52
Population: Analysis was based on the mRS. Overall number of participants analyzed included participants with available data of cartilage thickness in the cMTFC at Week 52.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GLPG1972 75 mg | Number of Participants Who Were Osteoarthritis (OA) Structural Progressors Based on Cartilage Thickness in the cMTFC Assessed by qMRI on the Target Knee | 22 Participants |
| GLPG1972 150 mg | Number of Participants Who Were Osteoarthritis (OA) Structural Progressors Based on Cartilage Thickness in the cMTFC Assessed by qMRI on the Target Knee | 34 Participants |
| GLPG1972 300 mg | Number of Participants Who Were Osteoarthritis (OA) Structural Progressors Based on Cartilage Thickness in the cMTFC Assessed by qMRI on the Target Knee | 25 Participants |
| Placebo | Number of Participants Who Were Osteoarthritis (OA) Structural Progressors Based on Cartilage Thickness in the cMTFC Assessed by qMRI on the Target Knee | 35 Participants |
Comparison: Estimate (Standard Error of log \[estimate\]) of the adjusted odds ratio between GLPG1972 dose regimen and placebo: between the proportions of participants with response: placebo versus GLPG1972 dose regimenp-value: 0.39695% CI: [0.84, 2.58]Logistic Model
Comparison: Estimate (Standard Error of log \[estimate\]) of the adjusted odds ratio between GLPG1972 dose regimen and placebo: between the proportions of participants with response: placebo versus GLPG1972 dose regimenp-value: 0.95195% CI: [0.53, 1.5]Logistic Model
Comparison: Estimate (Standard Error of log \[estimate\]) of the adjusted odds ratio between GLPG1972 dose regimen and placebo: between the proportions of participants with response: placebo versus GLPG1972 dose regimenp-value: 0.98595% CI: [0.64, 1.83]Logistic Model
Secondary
Number of Participants Who Were Responders Based on the Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Criteria
OMERACT-OARSI criteria involves improvement based on WOMAC pain and function subscales and PGA. The responders according to OMERACT-OARSI criteria were participants who had: * A high improvement in pain or in function ≥ 50% and absolute change ≥ 20, OR * Improvement in at least 2 of the 3 following: * Pain ≥ 20% and absolute change ≥ 10 * Function ≥ 20% and absolute change ≥ 10 * Patient's global assessment ≥ 20% and absolute change ≥ 10. WOMAC pain subscale score: range of 0 to 20, higher scores indicating more pain, WOMAC physical function subscale score: range of 0 to 68, higher scores indicating worse physical function), PGA: The participant was asked Considering all the ways in which your knee osteoarthritis affects you, please rate on this 100 mm scale how well you are doing today. The participants rated disease activity by marking on a 100-mm VAS, with 0 being no pain and 100 being extreme pain. Higher score indicated higher disease activity.
Time frame: Week 52
Population: Analysis was based on the mRS. Overall number of participants analyzed included participants with available data of WOMAC pain and function subscales and PGA at Week 52.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GLPG1972 75 mg | Number of Participants Who Were Responders Based on the Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Criteria | 125 Participants |
| GLPG1972 150 mg | Number of Participants Who Were Responders Based on the Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Criteria | 119 Participants |
| GLPG1972 300 mg | Number of Participants Who Were Responders Based on the Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Criteria | 103 Participants |
| Placebo | Number of Participants Who Were Responders Based on the Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Criteria | 127 Participants |
Comparison: Estimate (Standard Error of log \[estimate\]) of the adjusted odds ratio between GLPG1972 dose regimen and placebo: between the proportions of participants with response: placebo versus GLPG1972 dose regimen.p-value: 0.99195% CI: [0.7, 1.58]Logistic Model
Comparison: Estimate (Standard Error of log \[estimate\]) of the adjusted odds ratio between GLPG1972 dose regimen and placebo: between the proportions of participants with response: placebo versus GLPG1972 dose regimen.p-value: 0.99295% CI: [0.64, 1.43]Logistic Model
Comparison: Estimate (Standard Error of log \[estimate\]) of the adjusted odds ratio between GLPG1972 dose regimen and placebo: between the proportions of participants with response: placebo versus GLPG1972 dose regimen.p-value: 0.65395% CI: [0.55, 1.23]Logistic Model
Secondary
Number of Participants With Treatment-emergent Adverse Event (TEAE)
TEAEs were defined as all adverse events (AEs) that occurred: * between first IMP intake date (included) and last visit of participant, or * before first IMP intake date and that worsened (in terms of intensity) or became serious according to investigator opinion between first IMP intake date (included) and last visit of participant. Number of participants with at least 1 TEAE (serious or non-serious) are reported.
Time frame: Baseline up to 2-weeks after last dose of IMP (up to Week 54)
Population: Safety Set: All participants having taken at least one dose of IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GLPG1972 75 mg | Number of Participants With Treatment-emergent Adverse Event (TEAE) | 174 Participants |
| GLPG1972 150 mg | Number of Participants With Treatment-emergent Adverse Event (TEAE) | 177 Participants |
| GLPG1972 300 mg | Number of Participants With Treatment-emergent Adverse Event (TEAE) | 174 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Event (TEAE) | 174 Participants |
Secondary
Plasma Concentrations of GLPG1972
Time frame: Pre-dose at Weeks 4, 12, and 52; Pre-dose and one post-dose sample (2-4 hours interval) at Week 28; one post dose sample (interval 4-8 hours) at Week 40
Population: Overall number of participants included participants with available data for plasma concentrations of GLPG1972. Number of participants analyzed included participants with available data for plasma concentrations of GLPG1972 at individual timepoints. As participants in the placebo arm did not receive GLPG1972, measurement of plasma concentrations of GLPG1972 for placebo arm is not applicable.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GLPG1972 75 mg | Plasma Concentrations of GLPG1972 | Week 4: Pre-dose | 0.445 μg/mL | Standard Deviation 0.319 |
| GLPG1972 75 mg | Plasma Concentrations of GLPG1972 | Week 12: Pre-dose | 0.474 μg/mL | Standard Deviation 0.685 |
| GLPG1972 75 mg | Plasma Concentrations of GLPG1972 | Week 28: Pre-dose | 0.457 μg/mL | Standard Deviation 0.409 |
| GLPG1972 75 mg | Plasma Concentrations of GLPG1972 | Week 28: 2-4 hours post-dose | 1.399 μg/mL | Standard Deviation 0.668 |
| GLPG1972 75 mg | Plasma Concentrations of GLPG1972 | Week 40: 4-8 hours post-dose | 1.54 μg/mL | Standard Deviation 0.678 |
| GLPG1972 75 mg | Plasma Concentrations of GLPG1972 | Week 52: Pre-dose | 0.603 μg/mL | Standard Deviation 0.6 |
| GLPG1972 150 mg | Plasma Concentrations of GLPG1972 | Week 52: Pre-dose | 1.12 μg/mL | Standard Deviation 1.048 |
| GLPG1972 150 mg | Plasma Concentrations of GLPG1972 | Week 4: Pre-dose | 1 μg/mL | Standard Deviation 0.946 |
| GLPG1972 150 mg | Plasma Concentrations of GLPG1972 | Week 28: 2-4 hours post-dose | 2.609 μg/mL | Standard Deviation 1.022 |
| GLPG1972 150 mg | Plasma Concentrations of GLPG1972 | Week 40: 4-8 hours post-dose | 3.13 μg/mL | Standard Deviation 1.2 |
| GLPG1972 150 mg | Plasma Concentrations of GLPG1972 | Week 12: Pre-dose | 0.952 μg/mL | Standard Deviation 0.794 |
| GLPG1972 150 mg | Plasma Concentrations of GLPG1972 | Week 28: Pre-dose | 0.857 μg/mL | Standard Deviation 0.696 |
| GLPG1972 300 mg | Plasma Concentrations of GLPG1972 | Week 12: Pre-dose | 1.788 μg/mL | Standard Deviation 1.51 |
| GLPG1972 300 mg | Plasma Concentrations of GLPG1972 | Week 28: Pre-dose | 1.714 μg/mL | Standard Deviation 1.206 |
| GLPG1972 300 mg | Plasma Concentrations of GLPG1972 | Week 52: Pre-dose | 2.132 μg/mL | Standard Deviation 1.597 |
| GLPG1972 300 mg | Plasma Concentrations of GLPG1972 | Week 28: 2-4 hours post-dose | 4.764 μg/mL | Standard Deviation 1.912 |
| GLPG1972 300 mg | Plasma Concentrations of GLPG1972 | Week 4: Pre-dose | 2.013 μg/mL | Standard Deviation 1.468 |
| GLPG1972 300 mg | Plasma Concentrations of GLPG1972 | Week 40: 4-8 hours post-dose | 5.664 μg/mL | Standard Deviation 2.425 |