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

Phase 2

Completed

• Conditions: Osteoarthritis
• Interventions: Drug: GLPG1972; Drug: Placebo

• Registration Number: NCT03595618
• Lead Sponsor: Galapagos NV

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-07-11
• Study First Submitted QC: 2018-07-20
• Study First Posted: 2018-07-23
• Study Start: 2018-08-14
• Primary Completion: 2020-07-14
• Study Completion: 2020-07-14
• Results First Submitted: 2021-04-20
• Results First Submitted QC: 2021-04-20
• Results First Posted: 2021-05-12
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-27
• Last Update Posted: 2021-07-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 932

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GLPG1972 300 mg	GLPG1972	Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.
Placebo	Placebo	Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
GLPG1972 75 mg	Placebo	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	Placebo	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 75 mg	GLPG1972	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	GLPG1972	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Plasma Concentrations of GLPG1972	Pre-dose at Weeks 4, 12, and 52; Pre-dose and one post-dose sample (2-4 hours interval) at Week 28; one post dose sample (interval 4-8 hours) at Week 40
Number of Participants With Treatment-emergent Adverse Event (TEAE)	Baseline up to 2-weeks after last dose of IMP (up to Week 54)	TEAEs were defined as all adverse events (AEs) that occurred: * between first IMP intake date (included) and last visit of participant, or; * before first IMP intake date and that worsened (in terms of intensity) or became serious according to investigator opinion between first IMP intake date (included) and last visit of participant.; Number of participants with at least 1 TEAE (serious or non-serious) are reported.
Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 28	Baseline, Week 28
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.
Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 52	Baseline, Week 52
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.
Number of Participants Who Were Osteoarthritis (OA) Structural Progressors Based on Cartilage Thickness in the cMTFC Assessed by qMRI on the Target Knee	Week 52	A "structural progressor" was defined as a participant who had an 8% cartilage loss in cMTFC. Number of participants who met the criteria of "structural progressor" at Week 52 are provided.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52	Baseline, Week 52	Western Ontario and McMaster Universities Osteoarthritis Index is a questionnaire designed to assess health status and health outcomes in participants with OA of the knee. The questionnaire contains 24 questions targeting areas of pain, stiffness, and physical function. Pain subscale includes 5 items rated on a Likert scale of 0 (none) to 4 (extreme) with a total range of 0-20 with higher scores indicating worse symptoms and function. Stiffness subscale includes 2 items rated on a Likert scale of 0 (none) to 4 (extreme) with a total range of 0-8 with higher scores indicating worse symptoms and function. Physical function subscale includes 17 items rated on a Likert scale of 0 (none) to 4 (extreme) with a total range of 0-68 with higher scores indicating worse symptoms and function. The total score is the sum of all subscales (range: 0 to 96) with higher scores indicating worse symptoms and function.
Change From Baseline in Pain Assessment in the Target Knee as Measured by Visual Analog Scale (VAS) to Week 52	Baseline, Week 52	The participant was asked "how would you rate the pain felt in the selected knee within the last 48 hours?". The participants rated the pain by marking the level of pain on a 100-mm VAS, with 0 being no pain and 100 being extreme pain. Higher score indicated higher pain intensity.
Change From Baseline in Patient Global Assessment (PGA) of Disease Activity as Measured by VAS to Week 52	Baseline, Week 52	The participant was asked "Considering all the ways in which your knee osteoarthritis affects you, please rate on this 100 mm scale how well you are doing today". The participants rated the disease activity by marking on a 100-mm VAS, with 0 being no pain and 100 being extreme pain. Higher score indicated higher disease activity.
Number of Participants Who Were Responders Based on the Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Criteria	Week 52	OMERACT-OARSI criteria involves improvement based on WOMAC pain and function subscales and PGA. The responders according to OMERACT-OARSI criteria were participants who had: * A high improvement in pain or in function ≥ 50% and absolute change ≥ 20, OR; * Improvement in at least 2 of the 3 following: * Pain ≥ 20% and absolute change ≥ 10; * Function ≥ 20% and absolute change ≥ 10; * Patient's global assessment ≥ 20% and absolute change ≥ 10.; WOMAC pain subscale score: range of 0 to 20, higher scores indicating more pain,; WOMAC physical function subscale score: range of 0 to 68, higher scores indicating worse physical function),; PGA: The participant was asked "Considering all the ways in which your knee osteoarthritis affects you, please rate on this 100 mm scale how well you are doing today". The participants rated disease activity by marking on a 100-mm VAS, with 0 being no pain and 100 being extreme pain. Higher score indicated higher disease activity.
Change From Baseline in Cartilage Thickness of the Total Tibiofemoral Compartment (tTFC) of the Target Knee by qMRI to Week 52	Baseline, Week 52	Reduction of cartilage loss was measured by cartilage thickness of the tTFC of the target knee using qMRI.

Trial Locations

Locations (44)

Central Research Associates, Inc.; 🇺🇸 Birmingham, Alabama, United States

Achieve Clinical Research, LLC; 🇺🇸 Birmingham, Alabama, United States

Elite Clinical Studies; 🇺🇸 Phoenix, Arizona, United States

Hope Research Institute, LLC - Arizona; 🇺🇸 Phoenix, Arizona, United States

Arizona Research Center; 🇺🇸 Phoenix, Arizona, United States

Clinical Research Consortium Arizona; 🇺🇸 Tempe, Arizona, United States

Samy Metyas MD, Inc - Covina Arthritis Clinic; 🇺🇸 Covina, California, United States

TriWest Research Associates, LLC; 🇺🇸 El Cajon, California, United States

BioSolutions Clinical Research Center; 🇺🇸 La Mesa, California, United States

The Helm Center for Pain Management; 🇺🇸 Laguna Hills, California, United States

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