Roccella: A Study to Assess Efficacy and Safety of GLPG1972/S201086 in Participants With Knee Osteoarthritis

• Sponsor: Galapagos NV (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03595618
• Collaborator: Institut de Recherches Internationales Servier (Other)
• Enrollment: 932
• Locations: 44
• Arms: 4
• Actual Duration (Months): 23
• Patients Per Site: 21.2
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis	Drug: GLPG1972; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 932 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of 3 Doses of S201086/GLPG1972 Administered Orally Once Daily in Patients With Knee Osteoarthritis. A 52-week International, Multi-regional, Multi-center, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study
• Actual Study Start Date: Aug 14, 2018
• Actual Primary Completion Date: Jul 14, 2020
• Actual Study Completion Date: Jul 14, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: GLPG1972; Film-coated tablets of GLPG1972 for oral use.; Drug: Placebo; Film-coated tablets of matching placebo for oral use.
Experimental: 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.	Drug: GLPG1972; Film-coated tablets of GLPG1972 for oral use.; Drug: Placebo; Film-coated tablets of matching placebo for oral use.
Experimental: GLPG1972 300 mg Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Drug: GLPG1972; Film-coated tablets of GLPG1972 for oral use.
Placebo Comparator: Placebo Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.	Drug: Placebo; Film-coated tablets of matching placebo for oral use.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 28 [Baseline, Week 28]

8. Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 52 [Baseline, Week 52]

9. 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.

10. 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.

11. 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]

12. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Research Associates, Inc.	Birmingham	Alabama	United States	35205
2	Achieve Clinical Research, LLC	Birmingham	Alabama	United States	35216
3	Elite Clinical Studies	Phoenix	Arizona	United States	85018
4	Hope Research Institute, LLC - Arizona	Phoenix	Arizona	United States	85018
5	Arizona Research Center	Phoenix	Arizona	United States	85053
6	Clinical Research Consortium Arizona	Tempe	Arizona	United States	85283
7	Samy Metyas MD, Inc - Covina Arthritis Clinic	Covina	California	United States	91723
8	TriWest Research Associates, LLC	El Cajon	California	United States	92020
9	BioSolutions Clinical Research Center	La Mesa	California	United States	91942
10	The Helm Center for Pain Management	Laguna Hills	California	United States	92637
11	Stanford University	Palo Alto	California	United States	94304
12	Artemis Institute for Clinical Research - San Diego	San Diego	California	United States	92103
13	Artemis Institute for Clinical Research - San Marcos	San Marcos	California	United States	92078
14	Encompass Clinical Research	Spring Valley	California	United States	91978
15	Center for Musculoskeletal Care - Yale Medicine	New Haven	Connecticut	United States	06519
16	Avail Clinical Research, LLC	DeLand	Florida	United States	32720
17	Clinical Physiology Associates Clinical Study Center	Fort Myers	Florida	United States	33912
18	Health Awareness, Inc	Jupiter	Florida	United States	33458
19	Bioclinica Research	Orlando	Florida	United States	32806
20	Stedman Clinical Trials, LLC	Tampa	Florida	United States	33613
21	Compass Research, LLC	The Villages	Florida	United States	32162
22	Injury Care Research, LLC	Boise	Idaho	United States	83713
23	Millennium Pain Center - Bloomington	Bloomington	Illinois	United States	61704
24	Northwestern University	Chicago	Illinois	United States	60611
25	Medisphere Medical Research Center	Evansville	Indiana	United States	47714
26	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
27	Phoenix Medical Reasearch	Prairie Village	Kansas	United States	66208
28	Central Kentucky Research Associates, Inc.	Lexington	Kentucky	United States	40509
29	Medpharmics	Metairie	Louisiana	United States	70006
30	The Center for Rheumatology and Bone Research	Wheaton	Maryland	United States	20902
31	Tufts Medical Center	Boston	Massachusetts	United States	02111
32	Clinical Research Consortium Nevada	Las Vegas	Nevada	United States	89119
33	NY Scientific	Brooklyn	New York	United States	11235
34	Rochester Clinical Research, Inc.	Rochester	New York	United States	14609
35	Upstate Clinical Research Associates	Williamsville	New York	United States	14221
36	Lillestol Research, LCC	Fargo	North Dakota	United States	58103
37	Optimed Research, LTD	Columbus	Ohio	United States	43235
38	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
39	Pioneer Research Solutions Inc.	Houston	Texas	United States	77099
40	Diagnostics Research Group	San Antonio	Texas	United States	78229
41	Advanced Clinical Research	West Jordan	Utah	United States	84088
42	Charlottesville Medical Research Center, LCC	Charlottesville	Virginia	United States	22911
43	Health Research of Hampton Roads, Inc. - Newport News	Newport News	Virginia	United States	23606
44	Clinical Research Associates of Tidewater	Norfolk	Virginia	United States	23507

Sponsors and Collaborators

• Galapagos NV
• Institut de Recherches Internationales Servier

Investigators

• Study Director: Galapagos Study Director, Galapagos NV

Study Documents (Full-Text)

• Study Protocol - Dec 9, 2019
• Statistical Analysis Plan - Sep 29, 2020

More Information

Publications

None provided.

• Responsible Party: Galapagos NV
• ClinicalTrials.gov Identifier: NCT03595618
• Other Study ID Numbers: GLPG1972-CL-201; 2017-004581-10; U1111-1205-0321
• First Posted: Jul 23, 2018
• Last Update Posted: Jul 28, 2021
• Last Verified: Jul 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee

Study Results

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 Detail	A total of 3319 participants were screened and 932 participants were randomized and 931 participants were treated.

Arm/Group Title	GLPG1972 75 mg	GLPG1972 150 mg	GLPG1972 300 mg	Placebo
Arm/Group Description	Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	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.	Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Period Title: Overall Study
STARTED	234	231	233	234
Treated	234	231	232	234
COMPLETED	191	191	177	200
NOT COMPLETED	43	40	56	34

Baseline Characteristics

Arm/Group Title	GLPG1972 75 mg	GLPG1972 150 mg	GLPG1972 300 mg	Placebo	Total
Arm/Group Description	Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	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.	Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.	Total of all reporting groups
Overall Participants	234	231	233	234	932
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.9 (7.5)	63.2 (7.2)	62.1 (7.4)	63.3 (7.1)	62.9 (7.3)
Sex: Female, Male (Count of Participants)
Female	164 70.1%	165 71.4%	154 66.1%	163 69.7%	646 69.3%
Male	70 29.9%	66 28.6%	79 33.9%	71 30.3%	286 30.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	52 22.2%	52 22.5%	36 15.5%	53 22.6%	193 20.7%
Not Hispanic or Latino	182 77.8%	179 77.5%	197 84.5%	181 77.4%	739 79.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.4%	0 0%	2 0.9%	0 0%	3 0.3%
Asian	31 13.2%	28 12.1%	30 12.9%	32 13.7%	121 13%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.4%	0 0%	0 0%	1 0.1%
Black or African American	27 11.5%	19 8.2%	25 10.7%	25 10.7%	96 10.3%
White	167 71.4%	177 76.6%	168 72.1%	171 73.1%	683 73.3%
More than one race	8 3.4%	6 2.6%	8 3.4%	6 2.6%	28 3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Cartilage Thickness of the Central Medial Tibiofemoral Compartment (cMTFC) of the Target Knee (mm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm]	3.25316 (0.75857)	3.23101 (0.75531)	3.33075 (0.79839)	3.18554 (0.81513)	3.24996 (0.78289)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Cartilage Thickness of the cMTFC as Assessed by qMRI on the Target Knee to Week 52
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GLPG1972 75 mg	GLPG1972 150 mg	GLPG1972 300 mg	Placebo
Arm/Group Description	Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	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.	Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Measure Participants	162	158	151	172
Mean (Standard Deviation) [mm]	-0.06791 (0.20169)	-0.09693 (0.26839)	-0.08545 (0.21697)	-0.11562 (0.27275)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 75 mg, Placebo
	Comments	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 value
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.165
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.04514
	Confidence Interval	(2-Sided) 95%; -0.00317 to 0.09345
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.02465
	Estimation Comments	Two-sided 95% confidence interval of the estimate without Dunnett adjustment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 150 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.939
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.01200
	Confidence Interval	(2-Sided) 95%; -0.03868 to 0.06267
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.02585
	Estimation Comments	Two-sided 95% confidence interval of the estimate without Dunnett adjustment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 300 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.682
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.02329
	Confidence Interval	(2-Sided) 95%; -0.02641 to 0.07300
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.02536
	Estimation Comments	Two-sided 95% confidence interval of the estimate without Dunnett adjustment.

2. Secondary Outcome

Title	Number of Participants Who Were Osteoarthritis (OA) Structural Progressors Based on Cartilage Thickness in the cMTFC Assessed by qMRI on the Target Knee
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GLPG1972 75 mg	GLPG1972 150 mg	GLPG1972 300 mg	Placebo
Arm/Group Description	Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	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.	Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Measure Participants	162	158	151	172
Count of Participants [Participants]	22 9.4%	34 14.7%	25 10.7%	35 15%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 75 mg, Placebo
	Comments	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
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.396
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05)
	Method	Logistic Model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.47
	Confidence Interval	(2-Sided) 95%; 0.84 to 2.58
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.29
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 150 mg, Placebo
	Comments	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
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.951
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05)
	Method	Logistic Model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.53 to 1.50
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.26
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 300 mg, Placebo
	Comments	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
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.985
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05)
	Method	Logistic Model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.64 to 1.83
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment

3. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GLPG1972 75 mg	GLPG1972 150 mg	GLPG1972 300 mg	Placebo
Arm/Group Description	Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	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.	Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Measure Participants	233	230	231	234
Total score: Baseline	48.0 (15.2)	48.7 (15.0)	47.0 (15.2)	48.3 (14.5)
Total score: Change from baseline to Week 52	-16.3 (17.7)	-16.9 (17.7)	-16.1 (19.8)	-18.4 (18.9)
Pain subscore: Baseline	10.2 (3.2)	10.0 (3.1)	9.8 (3.1)	10.0 (3.2)
Pain subscore: Change from baseline to Week 52	-3.9 (4.1)	-3.7 (4.0)	-3.7 (4.2)	-4.1 (4.1)
Physical function subscore: Baseline	33.8 (11.2)	34.3 (11.2)	33.0 (11.6)	34.1 (10.7)
Physical function subscore: Change from baseline to Week 52	-11.2 (12.7)	-11.9 (13.0)	-10.9 (14.7)	-12.7 (13.9)
Stiffness subscore: Baseline	4.0 (1.7)	4.3 (1.7)	4.2 (1.6)	4.2 (1.6)
Stiffness subscore: Change from baseline to Week 52	-1.2 (2.1)	-1.3 (2.0)	-1.4 (2.0)	-1.5 (2.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 75 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.467
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -5.6 to 1.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.7
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 150 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.557
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05)
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 95%; -5.4 to 1.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.8
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 300 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.593
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 95%; -5.3 to 1.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.8
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 75 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.776
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 150 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.446
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 300 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.649
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -1.1 to 0.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.4
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 75 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.452
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -4.1 to 0.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.3
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 150 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.665
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -3.7 to 1.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.3
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 300 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.598
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -3.9 to 1.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.3
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 75 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.400
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05)
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 150 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.393
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05)
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 300 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.858
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05)
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment

4. Secondary Outcome

Title	Change From Baseline in Pain Assessment in the Target Knee as Measured by Visual Analog Scale (VAS) to Week 52
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GLPG1972 75 mg	GLPG1972 150 mg	GLPG1972 300 mg	Placebo
Arm/Group Description	Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	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.	Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Measure Participants	234	231	233	234
Baseline	63.3 (11.4)	63.8 (11.5)	63.3 (12.1)	63.5 (11.0)
Change from baseline to Week 52	-27.2 (24.3)	-25.6 (26.9)	-28.2 (27.1)	-28.9 (25.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 75 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.705
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.2
	Confidence Interval	(2-Sided) 95%; -7.1 to 2.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.5
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 150 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.243
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-4.1
	Confidence Interval	(2-Sided) 95%; -9.0 to 0.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.5
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 300 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.949
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 95%; -6.1 to 3.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.5
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

5. Secondary Outcome

Title	Change From Baseline in Patient Global Assessment (PGA) of Disease Activity as Measured by VAS to Week 52
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GLPG1972 75 mg	GLPG1972 150 mg	GLPG1972 300 mg	Placebo
Arm/Group Description	Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	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.	Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Measure Participants	232	230	232	233
Baseline	47.1 (18.3)	47.9 (19.0)	49.4 (17.5)	50.4 (19.2)
Change from baseline to Week 52	19.4 (30.0)	14.3 (30.7)	14.1 (28.4)	14.0 (31.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 75 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.890
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; -3.4 to 6.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.5
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 150 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.682
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -7.1 to 2.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.5
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 300 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -4.8 to 5.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.5
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

6. Secondary Outcome

Title	Number of Participants Who Were Responders Based on the Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Criteria
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GLPG1972 75 mg	GLPG1972 150 mg	GLPG1972 300 mg	Placebo
Arm/Group Description	Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	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.	Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Measure Participants	189	187	176	200
Count of Participants [Participants]	125 53.4%	119 51.5%	103 44.2%	127 54.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 75 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.991
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Logistic Model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.58
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.21
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 150 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.992
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Logistic Model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.64 to 1.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.21
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 300 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.653
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Logistic Model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95%; 0.55 to 1.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.21
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

7. Secondary Outcome

Title	Change From Baseline in Cartilage Thickness of the Total Tibiofemoral Compartment (tTFC) of the Target Knee by qMRI to Week 52
Description	Reduction of cartilage loss was measured by cartilage thickness of the tTFC of the target knee using qMRI.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

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/Group Title	GLPG1972 75 mg	GLPG1972 150 mg	GLPG1972 300 mg	Placebo
Arm/Group Description	Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	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.	Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Measure Participants	232	229	231	234
Baseline	6.49218 (1.02749)	6.57424 (1.02706)	6.51256 (0.97704)	6.45879 (1.01774)
Change from baseline to Week 52	-0.03572 (0.17673)	-0.02401 (0.20766)	-0.01678 (0.20934)	-0.06447 (0.23480)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 75 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.193
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.03779
	Confidence Interval	(2-Sided) 95%; -0.00448 to 0.08005
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.02156
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 150 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.256
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.03580
	Confidence Interval	(2-Sided) 95%; -0.00801 to 0.07962
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.02235
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 300 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.201
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.03884
	Confidence Interval	(2-Sided) 95%; -0.00514 to 0.08281
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.02243
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

8. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GLPG1972 75 mg	GLPG1972 150 mg	GLPG1972 300 mg	Placebo
Arm/Group Description	Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	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.	Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Measure Participants	234	229	232	234
Baseline	2343.32026 (371.23246)	2346.17547 (373.46086)	2354.77368 (385.91599)	2333.67525 (362.46041)
Change from baseline to Week 28	8.21893 (31.81812)	11.11178 (33.14557)	7.63991 (33.60899)	11.43549 (29.60810)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 75 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.627
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	3.12394
	Confidence Interval	(2-Sided) 95%; -3.02464 to 9.27252
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.13671
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 150 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.998
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.46842
	Confidence Interval	(2-Sided) 95%; -5.82659 to 6.76343
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.21111
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 300 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.449
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	4.11756
	Confidence Interval	(2-Sided) 95%; -2.30536 to 10.54049
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.27590
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

9. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GLPG1972 75 mg	GLPG1972 150 mg	GLPG1972 300 mg	Placebo
Arm/Group Description	Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	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.	Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Measure Participants	234	229	232	234
Baseline	2343.32026 (371.23246)	2346.17547 (373.46086)	2354.77368 (385.91599)	2333.67525 (362.46041)
Change from baseline to Week 52	15.45592 (31.22629)	22.06801 (42.85848)	20.78279 (34.96462)	18.08990 (35.93650)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 75 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.789
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05)
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	2.84781
	Confidence Interval	(2-Sided) 95%; -4.51643 to 10.21205
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.75674
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 150 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.661
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-3.64759
	Confidence Interval	(2-Sided) 95%; -11.19071 to 3.89553
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.84747
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 300 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.843
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	-2.55176
	Confidence Interval	(2-Sided) 95%; -10.04053 to 4.93701
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.81987
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

10. Secondary Outcome

Title	Change From Baseline in Joint Space Width (JSW) of the Target Knee to Week 52
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GLPG1972 75 mg	GLPG1972 150 mg	GLPG1972 300 mg	Placebo
Arm/Group Description	Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	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.	Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Measure Participants	234	230	232	233
Baseline	2.504 (0.779)	2.500 (0.783)	2.577 (0.840)	2.483 (0.859)
Change from baseline to Week 52	-0.087 (0.397)	-0.167 (0.506)	-0.113 (0.464)	-0.174 (0.470)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 75 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.141
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.0951
	Confidence Interval	(2-Sided) 95%; -0.0028 to 0.1929
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0499
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 150 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.981
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.0158
	Confidence Interval	(2-Sided) 95%; -0.0861 to 0.1177
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0519
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GLPG1972 300 mg, Placebo
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.349
	Comments	Two-sided adjusted p-value taking into account Dunnett adjustment (to be compared to 0.05).
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted mean difference
	Estimated Value	0.0753
	Confidence Interval	(2-Sided) 95%; -0.0286 to 0.1792
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0529
	Estimation Comments	Two-sided 95% Confidence Interval of the estimate without Dunnett adjustment.

11. Secondary Outcome

Title	Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study
Description	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

Outcome Measure Data

Analysis Population Description

Analysis was based on mRS.

Arm/Group Title	GLPG1972 75 mg	GLPG1972 150 mg	GLPG1972 300 mg	Placebo
Arm/Group Description	Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	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.	Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Measure Participants	234	231	233	234
Participants with at least one treatment	216 92.3%	213 92.2%	211 90.6%	212 90.6%
Anti-inflammatory and anti-rheumatic products	173 73.9%	167 72.3%	180 77.3%	178 76.1%
Analgesics	127 54.3%	135 58.4%	118 50.6%	128 54.7%
Anti-diarrheals, intestinal anti-inflammatory/anti-infective agents	0 0%	1 0.4%	1 0.4%	1 0.4%
Drugs for functional gastrointestinal disorders	1 0.4%	0 0%	0 0%	0 0%

12. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GLPG1972 75 mg	GLPG1972 150 mg	GLPG1972 300 mg
Arm/Group Description	Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	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.	Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.
Measure Participants	217	210	194
Week 4: Pre-dose	0.445 (0.319)	1 (0.946)	2.013 (1.468)
Week 12: Pre-dose	0.474 (0.685)	0.952 (0.794)	1.788 (1.51)
Week 28: Pre-dose	0.457 (0.409)	0.857 (0.696)	1.714 (1.206)
Week 28: 2-4 hours post-dose	1.399 (0.668)	2.609 (1.022)	4.764 (1.912)
Week 40: 4-8 hours post-dose	1.54 (0.678)	3.13 (1.2)	5.664 (2.425)
Week 52: Pre-dose	0.603 (0.6)	1.12 (1.048)	2.132 (1.597)

13. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Event (TEAE)
Description	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)

Outcome Measure Data

Analysis Population Description

Safety Set: All participants having taken at least one dose of IMP.

Arm/Group Title	GLPG1972 75 mg	GLPG1972 150 mg	GLPG1972 300 mg	Placebo
Arm/Group Description	Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	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.	Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Measure Participants	234	231	232	234
Count of Participants [Participants]	174 74.4%	177 76.6%	174 74.7%	174 74.4%

Adverse Events

Time Frame	Baseline up to 2-weeks after last dose of IMP (up to Week 54)
Adverse Event Reporting Description	TEAEs were defined as all 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. Analysis was based on the safety set. All serious AEs are reported, TEAEs are reported at a threshold of 3%.
Arm/Group Title	GLPG1972 75 mg		GLPG1972 150 mg		GLPG1972 300 mg		Placebo
Arm/Group Description	Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.		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.		Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.		Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
All Cause Mortality
	GLPG1972 75 mg		GLPG1972 150 mg		GLPG1972 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/234 (0%)		1/231 (0.4%)		0/232 (0%)		0/234 (0%)
Serious Adverse Events
	GLPG1972 75 mg		GLPG1972 150 mg		GLPG1972 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/234 (7.3%)		17/231 (7.4%)		18/232 (7.8%)		18/234 (7.7%)
Cardiac disorders
Atrial fibrillation	1/234 (0.4%)		1/231 (0.4%)		1/232 (0.4%)		0/234 (0%)
Myocarditis	0/234 (0%)		0/231 (0%)		1/232 (0.4%)		0/234 (0%)
Atrial flutter	1/234 (0.4%)		1/231 (0.4%)		0/232 (0%)		0/234 (0%)
Supraventricular tachycardia	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Acute myocardial infarction	0/234 (0%)		0/231 (0%)		0/232 (0%)		2/234 (0.9%)
Coronary artery occlusion	0/234 (0%)		0/231 (0%)		0/232 (0%)		1/234 (0.4%)
Coronary artery stenosis	0/234 (0%)		0/231 (0%)		0/232 (0%)		1/234 (0.4%)
Ear and labyrinth disorders
Vertigo	0/234 (0%)		1/231 (0.4%)		0/232 (0%)		0/234 (0%)
Eye disorders
Retinal detachment	0/234 (0%)		0/231 (0%)		1/232 (0.4%)		0/234 (0%)
Angle closure glaucoma	0/234 (0%)		0/231 (0%)		0/232 (0%)		1/234 (0.4%)
Macular degeneration	0/234 (0%)		0/231 (0%)		0/232 (0%)		1/234 (0.4%)
Gastrointestinal disorders
Food poisoning	0/234 (0%)		0/231 (0%)		1/232 (0.4%)		0/234 (0%)
Peritoneal cyst	0/234 (0%)		1/231 (0.4%)		0/232 (0%)		0/234 (0%)
Abdominal incarcerated hernia	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Intestinal obstruction	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Nausea	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
General disorders
Chills	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Non-cardiac chest pain	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Hepatobiliary disorders
Cholelithiasis	0/234 (0%)		1/231 (0.4%)		0/232 (0%)		0/234 (0%)
Cholecystitis acute	0/234 (0%)		0/231 (0%)		0/232 (0%)		2/234 (0.9%)
Bile duct stone	0/234 (0%)		0/231 (0%)		0/232 (0%)		1/234 (0.4%)
Drug-induced liver injury	0/234 (0%)		0/231 (0%)		0/232 (0%)		1/234 (0.4%)
Infections and infestations
COVID-19	0/234 (0%)		1/231 (0.4%)		1/232 (0.4%)		0/234 (0%)
Gastroenteritis	0/234 (0%)		0/231 (0%)		1/232 (0.4%)		0/234 (0%)
Pneumonia bacterial	0/234 (0%)		0/231 (0%)		1/232 (0.4%)		0/234 (0%)
Bronchitis	0/234 (0%)		1/231 (0.4%)		0/232 (0%)		0/234 (0%)
Pyelonephritis	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Urinary tract infection	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Appendiceal abscess	0/234 (0%)		0/231 (0%)		0/232 (0%)		1/234 (0.4%)
Burn infection	0/234 (0%)		0/231 (0%)		0/232 (0%)		1/234 (0.4%)
Injury, poisoning and procedural complications
Face injury	0/234 (0%)		0/231 (0%)		1/232 (0.4%)		0/234 (0%)
Procedural pain	0/234 (0%)		0/231 (0%)		1/232 (0.4%)		0/234 (0%)
Tendon rupture	0/234 (0%)		0/231 (0%)		1/232 (0.4%)		0/234 (0%)
Fall	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Femur fracture	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Wrist fracture	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Humerus fracture	0/234 (0%)		0/231 (0%)		0/232 (0%)		1/234 (0.4%)
Joint dislocation	0/234 (0%)		0/231 (0%)		0/232 (0%)		1/234 (0.4%)
Metabolism and nutrition disorders
Dehydration	0/234 (0%)		0/231 (0%)		1/232 (0.4%)		0/234 (0%)
Hypercalcaemia	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	2/234 (0.9%)		2/231 (0.9%)		3/232 (1.3%)		0/234 (0%)
Arthralgia	2/234 (0.9%)		1/231 (0.4%)		1/232 (0.4%)		0/234 (0%)
Back pain	0/234 (0%)		0/231 (0%)		1/232 (0.4%)		0/234 (0%)
Myopathy	0/234 (0%)		1/231 (0.4%)		0/232 (0%)		0/234 (0%)
Joint swelling	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer stage II	0/234 (0%)		0/231 (0%)		1/232 (0.4%)		0/234 (0%)
Invasive ductal breast carcinoma	0/234 (0%)		3/231 (1.3%)		0/232 (0%)		1/234 (0.4%)
Invasive papillary breast carcinoma	0/234 (0%)		1/231 (0.4%)		0/232 (0%)		0/234 (0%)
Endometrial adenocarcinoma	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Malignant melanoma in situ	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Basal cell carcinoma	0/234 (0%)		0/231 (0%)		0/232 (0%)		1/234 (0.4%)
Glottis carcinoma	0/234 (0%)		0/231 (0%)		0/232 (0%)		1/234 (0.4%)
Intraductal proliferative breast lesion	0/234 (0%)		0/231 (0%)		0/232 (0%)		1/234 (0.4%)
Nervous system disorders
Cervical cord compression	0/234 (0%)		0/231 (0%)		1/232 (0.4%)		0/234 (0%)
Sciatica	0/234 (0%)		0/231 (0%)		1/232 (0.4%)		0/234 (0%)
Ischaemic stroke	2/234 (0.9%)		1/231 (0.4%)		0/232 (0%)		1/234 (0.4%)
Cerebrovascular accident	0/234 (0%)		1/231 (0.4%)		0/232 (0%)		0/234 (0%)
Syncope	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		1/234 (0.4%)
Hypoaesthesia	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Psychiatric disorders
Depression suicidal	0/234 (0%)		0/231 (0%)		1/232 (0.4%)		0/234 (0%)
Renal and urinary disorders
Acute kidney injury	1/234 (0.4%)		0/231 (0%)		1/232 (0.4%)		0/234 (0%)
Ureterolithiasis	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Reproductive system and breast disorders
Ovarian cyst	0/234 (0%)		1/231 (0.4%)		0/232 (0%)		0/234 (0%)
Vaginal haemorrhage	1/234 (0.4%)		0/231 (0%)		0/232 (0%)		0/234 (0%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/234 (0%)		0/231 (0%)		1/232 (0.4%)		0/234 (0%)
Vascular disorders
Hypotension	0/234 (0%)		0/231 (0%)		1/232 (0.4%)		1/234 (0.4%)
Orthostatic hypotension	0/234 (0%)		0/231 (0%)		0/232 (0%)		1/234 (0.4%)
Other (Not Including Serious) Adverse Events
	GLPG1972 75 mg		GLPG1972 150 mg		GLPG1972 300 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	114/234 (48.7%)		124/231 (53.7%)		105/232 (45.3%)		130/234 (55.6%)
Gastrointestinal disorders
Nausea	3/234 (1.3%)		7/231 (3%)		11/232 (4.7%)		5/234 (2.1%)
Diarrhoea	3/234 (1.3%)		7/231 (3%)		4/232 (1.7%)		7/234 (3%)
General disorders
Oedema peripheral	6/234 (2.6%)		4/231 (1.7%)		2/232 (0.9%)		8/234 (3.4%)
Infections and infestations
Nasopharyngitis	21/234 (9%)		16/231 (6.9%)		22/232 (9.5%)		20/234 (8.5%)
Upper respiratory tract infection	7/234 (3%)		12/231 (5.2%)		6/232 (2.6%)		10/234 (4.3%)
Bronchitis	8/234 (3.4%)		7/231 (3%)		5/232 (2.2%)		6/234 (2.6%)
Urinary tract infection	6/234 (2.6%)		5/231 (2.2%)		4/232 (1.7%)		8/234 (3.4%)
Influenza	8/234 (3.4%)		4/231 (1.7%)		3/232 (1.3%)		7/234 (3%)
Injury, poisoning and procedural complications
Fall	14/234 (6%)		20/231 (8.7%)		16/232 (6.9%)		13/234 (5.6%)
Contusion	4/234 (1.7%)		7/231 (3%)		6/232 (2.6%)		6/234 (2.6%)
Investigations
Gamma-glutamyltransferase increased	3/234 (1.3%)		2/231 (0.9%)		16/232 (6.9%)		4/234 (1.7%)
Blood creatine phosphokinase increased	12/234 (5.1%)		7/231 (3%)		9/232 (3.9%)		8/234 (3.4%)
Alanine aminotransferase increased	4/234 (1.7%)		3/231 (1.3%)		10/232 (4.3%)		7/234 (3%)
Aspartate aminotransferase increased	4/234 (1.7%)		2/231 (0.9%)		10/232 (4.3%)		6/234 (2.6%)
C-reactive protein increased	1/234 (0.4%)		1/231 (0.4%)		9/232 (3.9%)		2/234 (0.9%)
Metabolism and nutrition disorders
Hypercholesterolaemia	3/234 (1.3%)		7/231 (3%)		4/232 (1.7%)		7/234 (3%)
Musculoskeletal and connective tissue disorders
Arthralgia	26/234 (11.1%)		34/231 (14.7%)		26/232 (11.2%)		19/234 (8.1%)
Back pain	11/234 (4.7%)		10/231 (4.3%)		6/232 (2.6%)		19/234 (8.1%)
Osteoarthritis	6/234 (2.6%)		10/231 (4.3%)		8/232 (3.4%)		10/234 (4.3%)
Pain in extremity	5/234 (2.1%)		7/231 (3%)		6/232 (2.6%)		4/234 (1.7%)
Musculoskeletal pain	3/234 (1.3%)		4/231 (1.7%)		8/232 (3.4%)		5/234 (2.1%)
Joint swelling	3/234 (1.3%)		7/231 (3%)		4/232 (1.7%)		4/234 (1.7%)
Nervous system disorders
Headache	15/234 (6.4%)		12/231 (5.2%)		11/232 (4.7%)		9/234 (3.8%)
Vascular disorders
Hypertension	6/234 (2.6%)		9/231 (3.9%)		12/232 (5.2%)		16/234 (6.8%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor must review and approve any results of the study or abstracts for professional meetings prepared by the investigator(s). Published data must not compromise the objectives of the study. Data from individual study centers in multicenter studies must not be published separately.