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

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

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.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis
• Intervention / Treatment: Drug: GLPG1972; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 932
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC
    • Birmingham, Alabama, United States, 35205
      • Central Research Associates, Inc.
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Arizona Research Center
    • Phoenix, Arizona, United States, 85018
      • Elite Clinical Studies
    • Phoenix, Arizona, United States, 85018
      • Hope Research Institute, LLC - Arizona
    • Tempe, Arizona, United States, 85283
      • Clinical Research Consortium Arizona
  • California
    • Covina, California, United States, 91723
      • Samy Metyas MD, Inc - Covina Arthritis Clinic
    • El Cajon, California, United States, 92020
      • TriWest Research Associates, LLC
    • La Mesa, California, United States, 91942
      • Biosolutions Clinical Research Center
    • Laguna Hills, California, United States, 92637
      • The Helm Center for Pain Management
    • Palo Alto, California, United States, 94304
      • Stanford University
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research - San Diego
    • San Marcos, California, United States, 92078
      • Artemis Institute for Clinical Research - San Marcos
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Center for Musculoskeletal Care - Yale Medicine
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Fort Myers, Florida, United States, 33912
      • Clinical Physiology Associates Clinical Study Center
    • Jupiter, Florida, United States, 33458
      • Health Awareness, Inc
    • Orlando, Florida, United States, 32806
      • Bioclinica Research
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials, LLC
    • The Villages, Florida, United States, 32162
      • Compass Research, LLC
  • Idaho
    • Boise, Idaho, United States, 83713
      • Injury Care Research, LLC
  • Illinois
    • Bloomington, Illinois, United States, 61704
      • Millennium Pain Center - Bloomington
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Medisphere Medical Research Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Prairie Village, Kansas, United States, 66208
      • Phoenix Medical Reasearch
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research Associates, Inc.
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • MedPharmics
  • Maryland
    • Wheaton, Maryland, United States, 20902
      • The Center for Rheumatology and Bone Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Clinical Research Consortium Nevada
  • New York
    • Brooklyn, New York, United States, 11235
      • NY Scientific
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc.
    • Williamsville, New York, United States, 14221
      • Upstate Clinical Research Associates
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Lillestol Research, LCC
  • Ohio
    • Columbus, Ohio, United States, 43235
      • Optimed Research, LTD
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • Texas
    • Houston, Texas, United States, 77099
      • Pioneer Research Solutions Inc.
    • San Antonio, Texas, United States, 78229
      • Diagnostics Research Group
  • Utah
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research Center, LCC
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads, Inc. - Newport News
    • Norfolk, Virginia, United States, 23507
      • Clinical Research Associates of Tidewater

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Cartilage Thickness of the cMTFC as Assessed by qMRI on the Target Knee to Week 52	Reduction in cartilage loss was assessed by cartilage thickness as measured in the medial cMTFC of the target knee using qMRI.	Baseline, Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Were Osteoarthritis (OA) Structural Progressors Based on Cartilage Thickness in the cMTFC Assessed by qMRI on the Target Knee	A "structural progressor" was defined as a participant who had an 8% cartilage loss in cMTFC. Number of participants who met the criteria of "structural progressor" at Week 52 are provided.	Week 52
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Total Score and Subscales Scores for Pain, Function, and Stiffness to Week 52	Western Ontario and McMaster Universities Osteoarthritis Index is a questionnaire designed to assess health status and health outcomes in participants with OA of the knee. The questionnaire contains 24 questions targeting areas of pain, stiffness, and physical function. Pain subscale includes 5 items rated on a Likert scale of 0 (none) to 4 (extreme) with a total range of 0-20 with higher scores indicating worse symptoms and function. Stiffness subscale includes 2 items rated on a Likert scale of 0 (none) to 4 (extreme) with a total range of 0-8 with higher scores indicating worse symptoms and function. Physical function subscale includes 17 items rated on a Likert scale of 0 (none) to 4 (extreme) with a total range of 0-68 with higher scores indicating worse symptoms and function. The total score is the sum of all subscales (range: 0 to 96) with higher scores indicating worse symptoms and function.	Baseline, Week 52
Change From Baseline in Pain Assessment in the Target Knee as Measured by Visual Analog Scale (VAS) to Week 52	The participant was asked "how would you rate the pain felt in the selected knee within the last 48 hours?". The participants rated the pain by marking the level of pain on a 100-mm VAS, with 0 being no pain and 100 being extreme pain. Higher score indicated higher pain intensity.	Baseline, Week 52
Change From Baseline in Patient Global Assessment (PGA) of Disease Activity as Measured by VAS to Week 52	The participant was asked "Considering all the ways in which your knee osteoarthritis affects you, please rate on this 100 mm scale how well you are doing today". The participants rated the disease activity by marking on a 100-mm VAS, with 0 being no pain and 100 being extreme pain. Higher score indicated higher disease activity.	Baseline, Week 52
Number of Participants Who Were Responders Based on the Outcome Measures in Rheumatology - Osteoarthritis Research Society International (OMERACT-OARSI) Criteria	OMERACT-OARSI criteria involves improvement based on WOMAC pain and function subscales and PGA. The responders according to OMERACT-OARSI criteria were participants who had: A high improvement in pain or in function ≥ 50% and absolute change ≥ 20, OR; Improvement in at least 2 of the 3 following:Pain ≥ 20% and absolute change ≥ 10Function ≥ 20% and absolute change ≥ 10Patient'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.	Week 52
Change From Baseline in Cartilage Thickness of the Total Tibiofemoral Compartment (tTFC) of the Target Knee by qMRI to Week 52	Reduction of cartilage loss was measured by cartilage thickness of the tTFC of the target knee using qMRI.	Baseline, Week 52
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 Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI to Week 52		Baseline, Week 52
Change From Baseline in Joint Space Width (JSW) of the Target Knee to Week 52	The JSW is the space measured between the 2 bones in the knee joint and this is assessed by x-ray.	Baseline, Week 52
Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study	Systemic analgesics included anti-inflammatory and anti-rheumatic products; analgesics; anti-diarrheals, intestinal, anti-inflammatory/anti-infective agents; and drugs for functional gastrointestinal disorders.	Baseline up to Week 52
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)	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.	Baseline up to 2-weeks after last dose of IMP (up to Week 54)

Collaborators and Investigators

• Sponsor: Galapagos NV
• Collaborators: Institut de Recherches Internationales Servier

Publications and helpful links

General Publications

• Brebion F, Gosmini R, Deprez P, Varin M, Peixoto C, Alvey L, Jary H, Bienvenu N, Triballeau N, Blanque R, Cottereaux C, Christophe T, Vandervoort N, Mollat P, Touitou R, Leonard P, De Ceuninck F, Botez I, Monjardet A, van der Aar E, Amantini D. Discovery of GLPG1972/S201086, a Potent, Selective, and Orally Bioavailable ADAMTS-5 Inhibitor for the Treatment of Osteoarthritis. J Med Chem. 2021 Mar 25;64(6):2937-2952. doi: 10.1021/acs.jmedchem.0c02008. Epub 2021 Mar 15.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 14, 2018
• Primary Completion (ACTUAL): July 14, 2020
• Study Completion (ACTUAL): July 14, 2020

Study Registration Dates

• First Submitted: July 11, 2018
• First Submitted That Met QC Criteria: July 20, 2018
• First Posted (ACTUAL): July 23, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 28, 2021
• Last Update Submitted That Met QC Criteria: July 27, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: GLPG1972-CL-201; 2017-004581-10 (EUDRACT_NUMBER); U1111-1205-0321 (OTHER: Universal Trial Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No