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

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ClinicalTrials.gov Identifier: NCT03595618
Recruitment Status : Completed
First Posted : July 23, 2018
Results First Posted : May 12, 2021
Last Update Posted : May 12, 2021
Sponsor:
Collaborator:
Institut de Recherches Internationales Servier
Information provided by (Responsible Party):
Galapagos NV

Tracking Information
First Submitted Date  ICMJE July 11, 2018
First Posted Date  ICMJE July 23, 2018
Results First Submitted Date  ICMJE April 20, 2021
Results First Posted Date  ICMJE May 12, 2021
Last Update Posted Date May 12, 2021
Actual Study Start Date  ICMJE August 14, 2018
Actual Primary Completion Date July 14, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 20, 2021)
Change From Baseline in Cartilage Thickness of the cMTFC as Assessed by qMRI on the Target Knee at Week 52 [ Time Frame: Baseline, Week 52 ]
Reduction in cartilage loss was assessed by cartilage thickness as measured in the medial cMTFC of the target knee using qMRI.
Original Primary Outcome Measures  ICMJE
 (submitted: July 20, 2018)
Change from baseline in cartilage thickness of the central medial tibiofemoral compartment (cMTFC) assessed by quantitative MRI on the target knee. [ Time Frame: Between Week 0 and Week 52 ]
To demonstrate the efficacy of at least one dose (among 3 doses) of S201086/GLPG1972 compared to placebo in reducing cartilage loss measured by cartilage thickness of the cMTFC of the target knee.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 20, 2021)
  • Number of Participants Who Were Osteoarthritis (OA) Structural Progressors Based on Cartilage Thickness in the cMTFC Assessed by qMRI on the Target Knee [ Time Frame: 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 at Week 52 [ Time Frame: 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) at Week 52 [ Time Frame: 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 at Week 52 [ Time Frame: 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 [ Time Frame: 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 at Week 52 [ Time Frame: Baseline, Week 52 ]
    Reduction of cartilage loss was measured by cartilage thickness of the tTFC of the target knee using qMRI.
  • Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI at Week 28 [ Time Frame: Baseline, Week 28 ]
  • Change From Baseline in Bone Area of the Medial Femoral Condyle Surface of the Target Knee by qMRI at Week 52 [ Time Frame: Baseline, Week 52 ]
  • Change From Baseline in Joint Space Width (JSW) of the Target Knee at Week 52 [ Time Frame: Baseline, Week 52 ]
    The JSW is the space measured between the 2 bones in the knee joint and this is assessed by x-ray.
  • Number of Participants Who Have Used at Least 1 Systemic Analgesic During the Study [ Time Frame: Baseline up to Week 52 ]
    Systemic analgesics included antiinflammatory and antirheumatic products; analgesics; antidiarrheals, intestinal, antiinflammatory/antiinfective agents; and drugs for functional gastrointestinal disorders.
  • 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 ]
  • Number of Participants With Treatment-emergent Adverse Event (TEAE) [ Time Frame: Baseline up to 2-weeks after last dose of IMP (up to Week 54) ]
    Treatment-emergent adverse events were defined as all adverse events:
    • which occurred between the first IMP intake date (included) and the last visit of the participant, or
    • which occur before the first IMP intake date and which worsen (in terms of intensity) or become serious according to the investigator opinion between the first IMP intake date (included) and the last visit of the participant.
    Number of participants with at least 1 treatment-emergent adverse event (serious or non-serious) are reported.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2018)
  • Proportion of OA structural progressors based on cartilage thickness in the central medial tibiofemoral compartment (cMTFC) assessed by quantitative MRI on the target knee. [ Time Frame: 52 weeks ]
    To assess efficacy of 3 doses of S201086/GLPG1972 versus placebo after 52 weeks of treatment on the proportion of structural progressors based on cartilage thickness in the CMTFC assessed of the target knee. A structural progressor is defined as a patient who had at least 8% cartilage loss in the cMTFC between baseline and Week 52.
  • Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscales scores for pain, function, and stiffness. [ Time Frame: Between Week 0 and Week 52 ]
    To assess efficacy of 3 doses of S201086/GLPG1972 versus placebo after 52 weeks on iso of pain, function, and stiffness measured with WOMAC.
  • Change from baseline in pain in the target knee measured with a 100-mm visual analog scale (VAS). [ Time Frame: Between Week 0 and Week 52 ]
    To assess efficacy of 3 doses of S201086/GLPG1972 versus placebo after 52 weeks of treatment on pain measured with a 100-mm visual analog scale (VAS).
  • Change from baseline in patient global assessment (PGA) of disease activity measured with 100-mm visual analog scale (VAS). [ Time Frame: Between Week 0 and Week 52 ]
    To assess efficacy of 3 doses of S201086/GLPG1972 versus placebo after 52 weeks of treatment on patient PGA of disease activity measured with 100-mm VAS.
  • Proportion of OMERACT-OARSI responders. [ Time Frame: Week 52 ]
    Based on OMERACT-OARSI Initiative: Osteoarthritis Research Society International set of responder criteria for OA clinical trials revisited Pham et al. 2004. A responder is defined according to WOMAC and PGA as a patient 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.
  • Change from baseline in cartilage thickness of the total tibiofemoral compartment (tTFC) of the target knee by quantitative MRI. [ Time Frame: Between Week 0 and Week 52. ]
    To assess efficacy of 3 doses of S201086/GLPG1972 versus placebo after 52 weeks of treatment on reduction of cartilage loss measured by cartilage thickness using quantitative MRI of the total tibiofemoral compartment (tTFC) of the target knee.
  • Change from baseline in bone area of the medial femoral condyle surface of the target knee by quantitative MRI. [ Time Frame: Between Week 0 and Week 28 ]
    To assess efficacy of 3 doses of S201086/GLPG1972 versus placebo on the bone area of the target knee using quantitative MRI of the medial femoral condyle surface.
  • Change from baseline in bone area of the medial femoral condyle surface of the target knee by quantitative MRI. [ Time Frame: Between Week 0 and Week 52 ]
    To assess efficacy of 3 doses of S201086/GLPG1972 versus placebo on the bone area of the target knee using quantitative MRI of the medial femoral condyle surface.
  • The change from baseline in Joint Space Width (JSW) of the target knee measured by X-Ray. [ Time Frame: Between Week 0 and Week 52. ]
    To assess efficacy of 3 doses of S201086/GLPG1972 versus placebo after 52 weeks of treatment on the target knee using X-ray.
  • Pain: analgesic consumption throughout the study. [ Time Frame: Between Week 0 and Week 52. ]
    To assess efficacy of 3 doses of S201086/GLPG1972 versus placebo after 52 weeks of treatment on analgesic consumption.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess Efficacy and Safety of GLPG1972/S201086 in Participants With Knee Osteoarthritis
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Osteoarthritis
Intervention  ICMJE
  • Drug: GLPG1972
    Film-coated tablets of GLPG1972 for oral use.
  • Drug: Placebo
    Film-coated tablets of matching placebo for oral use.
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: GLPG1972
    • Drug: Placebo
  • 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.
    Interventions:
    • Drug: GLPG1972
    • Drug: Placebo
  • Experimental: GLPG1972 300 mg
    Participants received 4 film-coated tablets of GLPG1972 75 mg (total dose 300 mg), orally once daily for 52 weeks.
    Intervention: Drug: GLPG1972
  • Placebo Comparator: Placebo
    Participants received 4 film-coated tablets of GLPG1972 matching placebo, orally once daily for 52 weeks.
    Intervention: Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 20, 2021)
932
Original Estimated Enrollment  ICMJE
 (submitted: July 20, 2018)
852
Actual Study Completion Date  ICMJE July 14, 2020
Actual Primary Completion Date July 14, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03595618
Other Study ID Numbers  ICMJE GLPG1972-CL-201
2017-004581-10 ( EudraCT Number )
U1111-1205-0321 ( Other Identifier: Universal Trial Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Galapagos NV
Study Sponsor  ICMJE Galapagos NV
Collaborators  ICMJE Institut de Recherches Internationales Servier
Investigators  ICMJE
Study Director: Galapagos Study Director Galapagos NV
PRS Account Galapagos NV
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP