Trial Outcomes & Findings for A Study to Assess Efficacy and Safety of GLPG1972/S201086 in Participants With Knee Osteoarthritis (NCT NCT03595618)

Last Updated: 2021-07-28

Results Overview

Reduction in cartilage loss was assessed by cartilage thickness as measured in the medial cMTFC of the target knee using qMRI.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

932 participants

Primary outcome timeframe

Baseline, Week 52

Results posted on

2021-07-28

Participant Flow

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.

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

Participant milestones

Participant milestones
Measure	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.	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.	GLPG1972 300 mg Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Placebo Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Overall Study STARTED	234	231	233	234
Overall Study Treated	234	231	232	234
Overall Study COMPLETED	191	191	177	200
Overall Study NOT COMPLETED	43	40	56	34

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.	GLPG1972 300 mg Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Placebo Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Overall Study Adverse Event	16	17	20	8
Overall Study Withdrawal by Subject	12	14	14	10
Overall Study Lost to Follow-up	6	4	5	6
Overall Study Protocol Violation	2	0	6	2
Overall Study Physician Decision	0	0	1	2
Overall Study Miscellaneous	7	5	10	6

Baseline Characteristics

Number of participants analyzed included participants with available data of cartilage thickness in the cMTFC at baseline.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GLPG1972 75 mg n=234 Participants Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	GLPG1972 150 mg n=231 Participants 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.	GLPG1972 300 mg n=233 Participants Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Placebo n=234 Participants Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.	Total n=932 Participants Total of all reporting groups
Age, Continuous	62.9 Years STANDARD_DEVIATION 7.5 • n=234 Participants	63.2 Years STANDARD_DEVIATION 7.2 • n=231 Participants	62.1 Years STANDARD_DEVIATION 7.4 • n=233 Participants	63.3 Years STANDARD_DEVIATION 7.1 • n=234 Participants	62.9 Years STANDARD_DEVIATION 7.3 • n=932 Participants
Sex: Female, Male Female	164 Participants n=234 Participants	165 Participants n=231 Participants	154 Participants n=233 Participants	163 Participants n=234 Participants	646 Participants n=932 Participants
Sex: Female, Male Male	70 Participants n=234 Participants	66 Participants n=231 Participants	79 Participants n=233 Participants	71 Participants n=234 Participants	286 Participants n=932 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	52 Participants n=234 Participants	52 Participants n=231 Participants	36 Participants n=233 Participants	53 Participants n=234 Participants	193 Participants n=932 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	182 Participants n=234 Participants	179 Participants n=231 Participants	197 Participants n=233 Participants	181 Participants n=234 Participants	739 Participants n=932 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=234 Participants	0 Participants n=231 Participants	0 Participants n=233 Participants	0 Participants n=234 Participants	0 Participants n=932 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=234 Participants	0 Participants n=231 Participants	2 Participants n=233 Participants	0 Participants n=234 Participants	3 Participants n=932 Participants
Race (NIH/OMB) Asian	31 Participants n=234 Participants	28 Participants n=231 Participants	30 Participants n=233 Participants	32 Participants n=234 Participants	121 Participants n=932 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=234 Participants	1 Participants n=231 Participants	0 Participants n=233 Participants	0 Participants n=234 Participants	1 Participants n=932 Participants
Race (NIH/OMB) Black or African American	27 Participants n=234 Participants	19 Participants n=231 Participants	25 Participants n=233 Participants	25 Participants n=234 Participants	96 Participants n=932 Participants
Race (NIH/OMB) White	167 Participants n=234 Participants	177 Participants n=231 Participants	168 Participants n=233 Participants	171 Participants n=234 Participants	683 Participants n=932 Participants
Race (NIH/OMB) More than one race	8 Participants n=234 Participants	6 Participants n=231 Participants	8 Participants n=233 Participants	6 Participants n=234 Participants	28 Participants n=932 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=234 Participants	0 Participants n=231 Participants	0 Participants n=233 Participants	0 Participants n=234 Participants	0 Participants n=932 Participants
Cartilage Thickness of the Central Medial Tibiofemoral Compartment (cMTFC) of the Target Knee	3.25316 mm STANDARD_DEVIATION 0.75857 • n=233 Participants • Number of participants analyzed included participants with available data of cartilage thickness in the cMTFC at baseline.	3.23101 mm STANDARD_DEVIATION 0.75531 • n=229 Participants • Number of participants analyzed included participants with available data of cartilage thickness in the cMTFC at baseline.	3.33075 mm STANDARD_DEVIATION 0.79839 • n=231 Participants • Number of participants analyzed included participants with available data of cartilage thickness in the cMTFC at baseline.	3.18554 mm STANDARD_DEVIATION 0.81513 • n=234 Participants • Number of participants analyzed included participants with available data of cartilage thickness in the cMTFC at baseline.	3.24996 mm STANDARD_DEVIATION 0.78289 • n=927 Participants • Number of participants analyzed included participants with available data of cartilage thickness in the cMTFC at baseline.

PRIMARY outcome

Timeframe: 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.

Reduction in cartilage loss was assessed by cartilage thickness as measured in the medial cMTFC of the target knee using qMRI.

Outcome measures

Outcome measures
Measure	GLPG1972 75 mg n=162 Participants Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	GLPG1972 150 mg n=158 Participants 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.	GLPG1972 300 mg n=151 Participants Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Placebo n=172 Participants Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
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	-0.09693 mm Standard Deviation 0.26839	-0.08545 mm Standard Deviation 0.21697	-0.11562 mm Standard Deviation 0.27275

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	GLPG1972 75 mg n=162 Participants Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	GLPG1972 150 mg n=158 Participants 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.	GLPG1972 300 mg n=151 Participants Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Placebo n=172 Participants Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
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	34 Participants	25 Participants	35 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	GLPG1972 75 mg n=233 Participants Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	GLPG1972 150 mg n=230 Participants 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.	GLPG1972 300 mg n=231 Participants Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Placebo n=234 Participants Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
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	48.7 score on a scale Standard Deviation 15.0	47.0 score on a scale Standard Deviation 15.2	48.3 score on a scale Standard Deviation 14.5
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	-16.9 score on a scale Standard Deviation 17.7	-16.1 score on a scale Standard Deviation 19.8	-18.4 score on a scale Standard Deviation 18.9
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	4.3 score on a scale Standard Deviation 1.7	4.2 score on a scale Standard Deviation 1.6	4.2 score on a scale Standard Deviation 1.6
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	-1.3 score on a scale Standard Deviation 2.0	-1.4 score on a scale Standard Deviation 2.0	-1.5 score on a scale Standard Deviation 2.0
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	10.0 score on a scale Standard Deviation 3.1	9.8 score on a scale Standard Deviation 3.1	10.0 score on a scale Standard Deviation 3.2
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 Pain subscore: Change from baseline to Week 52	-3.9 score on a scale Standard Deviation 4.1	-3.7 score on a scale Standard Deviation 4.0	-3.7 score on a scale Standard Deviation 4.2	-4.1 score on a scale Standard Deviation 4.1
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	34.3 score on a scale Standard Deviation 11.2	33.0 score on a scale Standard Deviation 11.6	34.1 score on a scale Standard Deviation 10.7
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	-11.9 score on a scale Standard Deviation 13.0	-10.9 score on a scale Standard Deviation 14.7	-12.7 score on a scale Standard Deviation 13.9

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	GLPG1972 75 mg n=234 Participants Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	GLPG1972 150 mg n=231 Participants 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.	GLPG1972 300 mg n=233 Participants Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Placebo n=234 Participants Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
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	-25.6 mm Standard Deviation 26.9	-28.2 mm Standard Deviation 27.1	-28.9 mm Standard Deviation 25.0
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	63.8 mm Standard Deviation 11.5	63.3 mm Standard Deviation 12.1	63.5 mm Standard Deviation 11.0

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	GLPG1972 75 mg n=232 Participants Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	GLPG1972 150 mg n=230 Participants 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.	GLPG1972 300 mg n=232 Participants Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Placebo n=233 Participants Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
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	47.9 mm Standard Deviation 19.0	49.4 mm Standard Deviation 17.5	50.4 mm Standard Deviation 19.2
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 30.0	14.3 mm Standard Deviation 30.7	14.1 mm Standard Deviation 28.4	14.0 mm Standard Deviation 31.3

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	GLPG1972 75 mg n=189 Participants Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	GLPG1972 150 mg n=187 Participants 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.	GLPG1972 300 mg n=176 Participants Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Placebo n=200 Participants Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Number of Participants Who Were Responders Based on the Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Criteria	125 Participants	119 Participants	103 Participants	127 Participants

SECONDARY outcome

Timeframe: 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.

Reduction of cartilage loss was measured by cartilage thickness of the tTFC of the target knee using qMRI.

Outcome measures

Outcome measures
Measure	GLPG1972 75 mg n=232 Participants Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	GLPG1972 150 mg n=229 Participants 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.	GLPG1972 300 mg n=231 Participants Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Placebo n=234 Participants Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
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	6.57424 mm Standard Deviation 1.02706	6.51256 mm Standard Deviation 0.97704	6.45879 mm Standard Deviation 1.01774
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	-0.02401 mm Standard Deviation 0.20766	-0.01678 mm Standard Deviation 0.20934	-0.06447 mm Standard Deviation 0.23480

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	GLPG1972 75 mg n=234 Participants Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	GLPG1972 150 mg n=229 Participants 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.	GLPG1972 300 mg n=232 Participants Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Placebo n=234 Participants Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
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	2346.17547 mm^2 Standard Deviation 373.46086	2354.77368 mm^2 Standard Deviation 385.91599	2333.67525 mm^2 Standard Deviation 362.46041
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	11.11178 mm^2 Standard Deviation 33.14557	7.63991 mm^2 Standard Deviation 33.60899	11.43549 mm^2 Standard Deviation 29.60810

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	GLPG1972 75 mg n=234 Participants Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	GLPG1972 150 mg n=229 Participants 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.	GLPG1972 300 mg n=232 Participants Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Placebo n=234 Participants Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
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	2346.17547 mm^2 Standard Deviation 373.46086	2354.77368 mm^2 Standard Deviation 385.91599	2333.67525 mm^2 Standard Deviation 362.46041
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	22.06801 mm^2 Standard Deviation 42.85848	20.78279 mm^2 Standard Deviation 34.96462	18.08990 mm^2 Standard Deviation 35.93650

SECONDARY outcome

Timeframe: 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.

The JSW is the space measured between the 2 bones in the knee joint and this is assessed by x-ray.

Outcome measures

Outcome measures
Measure	GLPG1972 75 mg n=234 Participants Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	GLPG1972 150 mg n=230 Participants 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.	GLPG1972 300 mg n=232 Participants Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Placebo n=233 Participants Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Change From Baseline in Joint Space Width (JSW) of the Target Knee to Week 52 Baseline	2.504 mm Standard Deviation 0.779	2.500 mm Standard Deviation 0.783	2.577 mm Standard Deviation 0.840	2.483 mm Standard Deviation 0.859
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	-0.167 mm Standard Deviation 0.506	-0.113 mm Standard Deviation 0.464	-0.174 mm Standard Deviation 0.470

SECONDARY outcome

Timeframe: Baseline up to Week 52

Population: Analysis was based on mRS.

Systemic analgesics included anti-inflammatory and anti-rheumatic products; analgesics; anti-diarrheals, intestinal, anti-inflammatory/anti-infective agents; and drugs for functional gastrointestinal disorders.

Outcome measures

Outcome measures
Measure	GLPG1972 75 mg n=234 Participants Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	GLPG1972 150 mg n=231 Participants 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.	GLPG1972 300 mg n=233 Participants Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Placebo n=234 Participants Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study Analgesics	127 Participants	135 Participants	118 Participants	128 Participants
Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study Anti-diarrheals, intestinal anti-inflammatory/anti-infective agents	0 Participants	1 Participants	1 Participants	1 Participants
Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study Drugs for functional gastrointestinal disorders	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study Participants with at least one treatment	216 Participants	213 Participants	211 Participants	212 Participants
Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study Anti-inflammatory and anti-rheumatic products	173 Participants	167 Participants	180 Participants	178 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

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

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	GLPG1972 75 mg n=234 Participants Participants received 1 film-coated tablet of GLPG1972 75 mg and 3 GLPG1972 matching placebo tablets, orally once daily for 52 weeks.	GLPG1972 150 mg n=231 Participants 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.	GLPG1972 300 mg n=232 Participants Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.	Placebo n=234 Participants Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
Number of Participants With Treatment-emergent Adverse Event (TEAE)	174 Participants	177 Participants	174 Participants	174 Participants

Adverse Events

GLPG1972 75 mg

Serious events: 17 serious events

Other events: 114 other events

Deaths: 0 deaths

GLPG1972 150 mg

Serious events: 17 serious events

Other events: 124 other events

Deaths: 1 deaths

GLPG1972 300 mg

Serious events: 18 serious events

Other events: 105 other events

Deaths: 0 deaths

Placebo

Serious events: 18 serious events

Other events: 130 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Galapagos Medical Information

Galapagos NV

Phone: +32 15342900

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER