Osteoarthritis of the knee MedDRA version: 13.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Name: RGH-478 Capsule
Product Code: RGH-478
Pharmaceutical Form: Capsule
Current Sponsor code: RGH-478
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
P
Sponsors
Gedeon Richter Plc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male or female = 40 years of age on the day of signing informed consent; Diagnosis of OA of the knee for = 6 months before signing informed consent according to American College of Rheumatology (ACR) criteria with X-ray confirmation of Kellgren-Lawrence grade 2 or 3 in the femoro-tibial compartment at screening and functional capacity class of I-III; Pain of the index knee joint on more than 50% of days over the last month prior to screening requiring analgesic and/or anti-inflammatory treatment; Currently receiving regular analgesics treatment (defined as drug intake for = 4 days per week) for pain at the index knee joint. Analgesic treatment may include non-steroidal anti-inflammatory drugs ([NSAIDs] including cyclooxygenase-2 [COX-2] inhibitors), paracetamol, and/or weak opioids (e.g. tramadol) given at recommended dose ranges; A Western Ontario & McMaster Universities Index of Osteoarthritis (WOMAC) VA3.1 pain visual analogue scale (VAS) score at Screening (Visit 1) = 30 mm and = 80 mm; Willingness to abstain from use of NSAIDs (oral and topical other than the one given as study drug), other topical pain therapies (e.g., capsaicin), corticosteroids (systemic and intra-articular), viscosupplementation, and other pharmacological pain treatments during the study; Willingness to abstain from the use of the permitted rescue medication (paracetamol) for 24 hours prior to all study visits8) Female patients of childbearing potential must have a negative serum pregnancy test (serum beta-human chorionic gonadotropin) at screening unless they are surgically sterile or have been post-menopausal for = 1 year (12 consecutive months without menses); Women of childbearing potential must use a medically acceptable means of birth control and agree to continue its use during the study and for at least 4 weeks after the last dose of study drug. Medically acceptable forms of birth control include oral contraceptives, injectable or implantable methods, intrauterine devices, tubal ligation (if performed > 1 year before screening), or double barrier contraception. Sexually active male patients should be surgically sterile or agree to use a medically acceptable means of birth control; Able to understand and willing to sign the informed consent prior to screening evaluations and agree to the schedule of assessments. A WOMAC VA3.1 pain VAS score at Baseline (Visit 2) = 50 mm, with an increase of = 10 mm from Screening; A Patient’s Global Assessment (PGA) of disease activity at Baseline of fair, poor, or very poor; and Patients need to have a minimum of 2 daily pain assessments via IVRS during the Screening Period. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: Surgery, including arthroscopy, of the index knee joint within 3 months of screening or any scheduled surgery or painful procedure of the index knee joint during the course of the study; Intra-articular corticosteroid to the index knee joint within 3 months prior to screening or to any other joint within 4 weeks prior to screening; Hyaluronic acid intra-articular injection to the index knee joint within 6 months prior to screening; Systemic corticosteroids (oral, intramuscular, or intravenous) within 4 weeks prior to screening; Physical therapy and other non-pharmacological pain therapy unless dose was stable for = 1 months prior to screening or planning the initiation of such therapy during the study; Nutritional supplementation for OA (unless dose was stable for = 1 months prior to screening or planning the initiation of such therapy during the study; Radiotherapy for chronic articular pain within 3 months prior to screening or planning the initiation of such therapy during the study; Initiation of the use of medications for treating chronic pain (including anticonvulsants, tricyclic antidepressants, unselective serotonin reuptake inhibitors, norepinephrine reuptake inhibitors etc.) within 2 weeks prior to screening or planning the initiation of any new anti-pain therapy or treatment during the study; Initiation of the use of hypnotics or change in the dosing regimen of current hypnotics including benzodiazepines and non-benzodiazepine hypnotics within 2 weeks prior to screening; Current use of anticoagulant drugs or antiaggregants (including low-dose acetylsalicylic acid); BMI 39 and/or body weight <40 kg at screening; Clinically relevant history of hypersensitivity or allergy to study drug, celecoxib, or paracetamol or any of their excipients as well as existence of a medical condition or use of concomitant medication for which the use of celecoxib or paracetamol is contraindicated; Known hypersensitivity to sulphonamides; Had previously failed treatment with or showed intolerance to NSAIDs, including COX-2 inhibitors; History of asthma, acute rhinitis, angioedema, urticaria or other allergic-type reactions after taking acetylsalicylic acid, ibuprofen, or other NSAIDs, including COX-2 inhibitors; Any medical conditions other than pain due to OA that could interfere with study evaluations, e.g., anatomical deformities, fibromyalgia, chronic pain syndrome or other arthritic conditions other than OA of the knee; Known or clinically suspected infection with human immunodeficiency virus, hepatitis C or B viruses; Congestive heart failure; history of clinically significant cardiovascular disease including, but not limited to, myocardial infarction, unstable angina, peripheral arterial disease, and stroke or transient ischemic attack; uncontrolled hypertension ; Active or history of recurrent peptic ulcer/hemorrhage or gastrointestinal perforation; history of gastrointestinal bleeding, history of inflammatory bowel disease; History of congenital QTc prolongation or QTc duration at the screening electrocardiogram (ECG) = 450 msec for men or = 470 msec for women; Severe renal or hepatic insufficiency; Any clinically significant condition or laboratory result that in the Investigator’s judgment may affect efficacy or safety assessments or may compromise the patient’s safety during study participation, ; History of malignancy within the past 5 years (except for b
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to preliminarily evaluate the efficacy of RGH-478 compared with placebo in patients with osteoarthritis. ;Secondary Objective: The secondary objectives of this study are to assess the safety and tolerability of RGH-478 in patients with osteoarthritis.;Primary end point(s): The primary efficacy endpoint will be the change from baseline to V5 (Week 4) in the WOMAC VA3.1 pain VAS subscale.;Timepoint(s) of evaluation of this end point: The primary end point will be evaluated after the study has been completed, no iterim analysis will be performed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change from baseline at V3 (Week 1), V4 (Week 2), and V5 (Week 4) in the average daily pain intensity score evaluated on a Numeric Rating Scale (NRS); WOMAC VA3.1 Pain VAS subscale change from baseline at V3 (Week 1) and V4 (Week 2); WOMAC VA3.1 Stiffness subscale change from baseline at V3 (Week 1), V4 (Week 2), and V5 (Week 4); WOMAC VA3.1 Physical function subscale change from baseline at V3 (Week 1), V4 (Week 2), and V5 (Week 4); WOMAC VA3.1 Global Score change from baseline at V3 (Week 1), V4 (Week 2), and V5 (Week 4); Changes from baseline in PGA of disease activity scores at V3 (Week 1), V4 (Week 2), and V5 (Week 4); Percent of responders according to OMERACT-OARSI criteria at V3 (Week 1), V4 (Week 2), and V5 (Week 4); Use of rescue medication; Exploratory evaluation of selected biomarkers of inflammation and joint/cartilage damage; Adverse events; Vital signs (supine heart rate and blood pressure [systolic and diastolic]); Physical examination; 12-lead ECG; and Clinical laboratory tests (hematology, blood chemistry, and urinalysis). ;Timepoint(s) of evaluation of this end point: The secondary end points will be evaluated after the study has been completed, no iterim analysis will be performed. | — |
Countries
Hungary
Contacts
Public ContactGedeon Richter Plc.
Gedeon Richter Plc.
Outcome results
None listed