A Study to Assess the Analgesic Efficacy of ASP7962 in Patients With Pain Due to Osteoarthritis of the Knee

NCT02611466 | Completed Phase 2 DMC

• 2 other identifiers: 7962-CL-00222014-004996-22
• Study Type: interventional
• Target: 215
• Locations: 6 countries
• Sites: 34

Brief Summary

The purpose of the study is to evaluate the analgesic efficacy of ASP7962 relative to placebo. This study will also evaluate the efficacy of ASP7962 relative to placebo on pain on walking, function and stiffness; the time course of efficacy of ASP7962 relative to placebo; the improvement in overall patient status of ASP7962 relative to placebo as well as the safety and tolerability of ASP7962 relative to placebo.

Conditions

Osteoarthritis of the Knee; Chronic Lower Back Pain

Keywords

Osteoarthritis; ASP7962

Outcome Measures

Primary Outcomes (1)

• Change from Baseline to Week 4 in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Subscale Score

  WOMAC is a tri-dimensional, self-administered, patient-centered health status questionnaire designed to capture the elements of pain, stiffness and physical function in participants with OA of the knee and/or hip joints. The questionnaire consists of 24 questions, which are divided into three subscales: pain (5 questions), stiffness (2 questions) and physical function (17 questions). Each question is scored using 11-point NRS scale ranging from 0 (none) to 10 (extreme). The pain subscale contains five questions that ask about pain during the last 48 hours caused by arthritis in the index knee. A negative change indicates a reduction/improvement from baseline.

  Baseline and Week 4

Secondary Outcomes (19)

• Change from Baseline to End of Treatment (EOT) in WOMAC Pain Subscale Score

  Baseline and EOT (up to 4 weeks)

• Change from Baseline to EOT in WOMAC Physical Function Subscale Score

  Baseline and EOT (up to 4 weeks)

• Change from Baseline to EOT in WOMAC Stiffness Subscale Score

  Baseline and EOT (up to 4 weeks)

• Change from Baseline to EOT in WOMAC Total Score

  Baseline and EOT (up to 4 weeks)

• Change from Baseline to EOT in WOMAC Walking Pain Score

  Baseline and EOT (up to 4 weeks)

Study Arms (3)

ASP7962

EXPERIMENTAL

Participants receive 100 mg of ASP7962 orally twice daily for 4 weeks.

Drug: ASP7962

Naproxen

ACTIVE COMPARATOR

Participants receive 500 mg of naproxen orally twice daily for 4 weeks.

Drug: Naproxen

Placebo

PLACEBO COMPARATOR

Participants receive placebo orally twice daily for a period of 4 weeks.

Drug: Placebo

Interventions

ASP7962 DRUG

Participants receive ASP7962 100 mg orally twice daily, in the morning and evening with or without food (approximately 12 hours).

ASP7962

Naproxen DRUG

Participants receive naproxen 500 mg orally twice daily, in the morning and evening with or without food (approximately 12 hours).

Naproxen

Placebo DRUG

Participants receive matching placebo orally twice daily, in the morning and evening with or without food (approximately 12 hours).

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has a primary diagnosis of OA of the index knee with symptoms for at least 6 months prior to screening and patient meets American College of Rheumatology clinical classification criteria for OA of the knee, defined by the following:
• Knee pain and at least 3 of the following 6:
• Age \> 50 years
• Morning stiffness \< 30 minutes
• Crepitus on active motion
• Bony tenderness
• Bony enlargement
• No palpable warmth of synovium
• Patient has a radiographic image of the index knee (according to the minimum quality criteria for radiographic image as set by the central radiology reader) showing evidence of OA with a Kellgren-Lawrence grade ≥2 at screening (based on central reading).
• Patient has moderate to severe index knee pain (pain due to OA of the knee at least 5 days per week for the last 3 months prior to screening, as determined by patient's medical history).
• Patient is ambulatory and the index knee must not contain any orthopedic and/or prosthetic device.
• WOMAC pain subscale score (with a 48-hour recall period) in the index knee ≥ 4 at baseline (visit 2 predose, mean of all questions on pain subscale).
• WOMAC physical function subscale score ≥ 4 at baseline (visit 2 predose, mean of all questions on physical function subscale with a 48-hour recall period).
• Patient is willing to discontinue all current pain medications during the baseline and treatment periods (until day 57) (except for allowed rescue medications). Low dose aspirin for cardioprophylaxis is allowed.
• Patient is compliant with daily pain recording. Compliance with diary completion will be defined as daily average pain ratings on at least 5 days of the baseline period, of which at least 3 days are in the last 4 days prior to visit 2.

You may not qualify if:

• Medical History / Clinical Status:
• Patient has a history of suicide attempt or suicidal behavior. Suicidal ideation within the last 12 months (a response of "yes" to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale \[C-SSRS\]), or who are at significant risk to commit suicide, as judged by the investigator at screening and at the time of randomization.
• Patient has current or prior psychosis, major depressive disorder or other clinically significant psychiatric disorder.
• Patient has any clinically significant uncontrolled musculoskeletal disorder (with the exception of OA), cardiovascular, gastrointestinal, endocrinologic (diabetes mellitus is allowed if controlled \[glycated hemoglobin (HbA1c) ≤ 8.0%\] and no peripheral neuropathy), hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, dermatologic, renal and/or other major disease.
• Patient has an active malignancy or a history of malignancy (except for treated nonmelanoma skin cancer) within the past 5 years.
• Patient has a history of inflammatory arthritis, (including rheumatoid arthritis or a history of RPOA, osteonecrosis or avascular necrosis of bone and/or joints), or has other diagnoses that may increase the risk of RPOA (e.g., pre-existing atrophic OA, subchondral insufficiency fracture), or severe knee malalignment or any other joint-related condition that makes the patient unsuitable for study participation (e.g., joint pain that is disproportionately severe, or which has atypical features for OA pain, should trigger further medical evaluation to rule out subchondral insufficiency fracture).
• Patient has findings suggestive of RPOA or increased risk for RPOA on screening radiographs of either index or non-index joints (based on central reading).
• Patient has a history of shoulder surgery, clinically significant trauma or current symptoms, including pain or impaired range of motion at shoulder joint.
• Patient has a coagulopathy, is receiving anticoagulants or has been diagnosed with thrombocytopenia or a functional platelet disorder.
• Patient has a history of paracetamol intolerance, or existence of medical condition or use of concomitant medication for which paracetamol is contraindicated.
• Patient has any contraindication to naproxen including but not limited to:
• Known hypersensitivity to tramadol (a patient with intolerance or hypersensitivity is allowed, if the patient accepts to limit rescue medication toparacetamol).
• Asthma, rhinitis, nasal polyps, urticarial or allergic-type reactions after taking aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs).
• Anticipated coronary artery bypass graft surgery during the study.
• Active or history of peptic ulceration.

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead

Study Sites (34)

Site BE32003

Leuven, 3000, Belgium

Location

Site BE32002

Merksem, 2170, Belgium

Location

Site BE32004

Yvoir, 5530, Belgium

Location

Site CZ42006

Hradec Králové, 50341, Czechia

Location

Site CZ42003

Kunovice, 686 04, Czechia

Location

Site CZ42002

Prague, 14000, Czechia

Location

Site CZ42005

Prague, 14059, Czechia

Location

Site DE49007

Bayern, 80639, Germany

Location

Site DE49006

Berlin, 10629, Germany

Location

Site DE49004

Deggingen, 73326, Germany

Location

Site DE49003

Leipzig, 4108, Germany

Location

Site DE49001

Magdeburg, 39120, Germany

Location

Site DE49005

Munich, 80809, Germany

Location

Site HU36002

Baja, 6500, Hungary

Location

Site HU36008

Balatonfüred, 8230, Hungary

Location

Site HU36005

Békéscsaba, 5600, Hungary

Location

Site HU36007

Budapest, 1027, Hungary

Location

Site HU36006

Debrecen, 4032, Hungary

Location

Site HU36001

Esztergom, 2500, Hungary

Location

Site HU36003

Komárom, 2900, Hungary

Location

Site HU36009

Szeged, 6722, Hungary

Location

Site HU36004

Veszprém, 8200, Hungary

Location

Site ES34002

A Coruña, 15006, Spain

Location

Site ES34001

Barakaldo, 48903, Spain

Location

Site ES34008

Barcelona, 8028, Spain

Location

Site ES34012

Barcelona, 8034, Spain

Location

Site ES34003

Bilbao, 48013, Spain

Location

Site ES34005

Madrid, 28046, Spain

Location

Site ES34004

Santiago de Compostela, 15702, Spain

Location

Site ES34010

Valencia, 46015, Spain

Location

Site GB44006

London, NW3 2QG, United Kingdom

Location

Site GB44011

North Shields, NE29 8NH, United Kingdom

Location

Site GB44010

Oxfordshire, OX3 7LD, United Kingdom

Location

Site GB44012

West Midlands, WS11 5XY, United Kingdom

Location

Related Publications (1)

• Watt FE, Blauwet MB, Fakhoury A, Jacobs H, Smulders R, Lane NE. Tropomyosin-related kinase A (TrkA) inhibition for the treatment of painful knee osteoarthritis: results from a randomized controlled phase 2a trial. Osteoarthritis Cartilage. 2019 Nov;27(11):1590-1598. doi: 10.1016/j.joca.2019.05.029. Epub 2019 Jul 26.

  PMID: 31356878 DERIVED

Related Links

• Link to results on the Astellas Clinical Study Results website

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Interventions

Naproxen

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Medical Officer

  Astellas Pharma Europe B.V.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2015
• First Posted: November 20, 2015
• Study Start: February 16, 2016
• Primary Completion: August 28, 2017
• Study Completion: September 29, 2017
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

GB (4); ES (8); HU (9); BE (3); DE (6); CZ (4)