Osteoarthritis of the knee MedDRA version: 20.0 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859
Conditions
Interventions
Product Name: PRX167700H
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PXR167700H
Current Sponsor code: PXR167700H
Other
Sponsors
Proximagen Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Participants who have symptomatic primary knee OA for at least 3 months prior to Screening. Participants must have had pain in the target knee for = 14 days per month in the 3 months preceding screening. 2. A diagnosis of knee OA based on American College of Rheumatology criteria with X-ray confirmation (a Kellgren-Lawrence X-ray grade of 2 3) in the target joint. X-rays taken within the last 12 months may be used for confirmation. One knee should be designated as the target joint. The pain in the target knee joint should exceed the pain experienced in other joints (including the contralateral knee joint and/or ipsilateral hip joint) and pain experienced from any concomitant medical condition. 3. Stable oral NSAID therapy for the treatment of knee OA for at least 5 of 7 days each week for the 4 weeks preceding the Screening visit (Visit 1). Stable therapy is considered to be use of the same dose of the same NSAID for the required number of days each week. 4. A moderate to severe pain score of = 8 and = 16 in the target knee joint evaluated by the WOMAC Pain Score at the Screening Visit (Visit 1), at the start of the Placebo Run-in (Visit 2), and at Baseline (Visit 3, Day 0). 5. The same or worse pain at Baseline (Visit 3, Day 0) compared to their WOMAC Pain Score at the start of the Placebo Run-in (Visit 2). 6. Body Mass Index (BMI) between 18 and 40 kg/m2, inclusive. 7. Male or female participants between 50 and 75 years of age, inclusive. 8. Female participants are eligible to participate in the study if they meet one of the following criteria: a. They are not of child-bearing potential (ie, physiologically incapable of becoming pregnant, including any female who is postmenopausal as defined in Appendix 5) b. They are of child bearing potential, are not pregnant or lactating, are sexually active, and have a negative pregnancy test at Screening (Visit 1, serum test from central lab), Visit 2 (urine dipstick method in the clinic), and Baseline (Visit 3, urine dipstick method in the clinic). WOCBP who are sexually active must agree to use an highly effective contraception method during the study. A highly effective contraception method is defined as: i. Established use of oral, injected or implanted hormonal methods of contraception. ii. Placement of an intrauterine device (IUD) or intrauterine system (IUS). iii. Sole male partner is vasectomised. iv. Bilateral tubal occlusion. c. They are of childbearing potential, are not pregnant or lactating, are sexually abstinent, and have a negative pregnancy test at Screening (Visit 1, serum test from central lab), Visit 2 (urine dipstick method in the clinic), and Baseline (Visit 3, urine dipstick method in the clinic). WOCBP who are sexually abstinent at the start of the study must agree to remain abstinent for the duration of the study. 9. Able to provide written informed consent to participate in the study and, in the opinion of the investigator, able to read, comprehend and record information as required by the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes
Exclusion criteria
Exclusion criteria: 1. Causes of secondary arthritis of the knee, including septic arthritis, autoimmune joint disease, crystalline diseases, gout, articular fracture, and inherited disorders 2. Pain relating to the target joint that has characteristics of neuropathic pain (eg.shooting or burning pain, pins and needles, allodynia, or reflex sympathetic dystrophy) 3. Disease of the spine or of lower extremity joints (other than OA) which contribute to the pain in the target joint 4. Lower extremity surgery (including arthroscopy) within 6 months prior to Screening (V1) or scheduled for surgery of any kind during the study. 5. Significant injury to the target joint within 12 months prior to Screening (V1) 7. Active autoimmune disease or conditions requiring chronic immunosuppressive therapy, including rheumatoid arthritis, systemic lupus erythematous, multiple sclerosis, and organ transplant recipient. Note: abnormal laboratory values for autoimmunity markers in the absence of other signs and symptoms of autoimmune disease are not exclusionary 8. Known history of hypersensitivity or intolerance to paracetamol or NSAIDs 9. Known or current history of clinically relevant gastrointestinal bleeding or symptoms within the last 3 months consistent with silent or symptomatic gastrointestinal 10. Clinically significant illness other than OA within 3 months prior to Screening (V1) which might interfere with the conduct of the trial 11. History of malignancy within past 5 years (except for basal cell carcinoma or carcinoma-in-situ of the cervix treated with curative intent) 13. Poorly controlled hypertension at Screening (V1) defined as systolic blood pressure (SBP) > 160 mmHg and/or diastolic blood pressure (DBP) > 100 mmHg measured after 5 minutes rest in the supine position. A repeat measure is allowed for the increased blood pressure if judged by the investigator to be white coat syndrome. Initiation of anti-hypertensive medication(s) is permitted prior to study entry. Blood pressure must be re-assessed on 2 occasions separated by at least one hour. Mean SBP/DBP values must be < or =160/100 for eligibility at screening 15. Substantial renal dysfunction, defined as creatinine clearance calculated using Cockroft Gault equation < 60 mL/min 20. Participants with any active medical condition or previous major abdominal surgery or procedure that might, in the investigator's opinion, have a significant effect on drug absorption, distribution, metabolism, or excretion 22. Use of analgesics other than NSAIDs for the treatment of knee OA for at least 25 days out of 30 days preceding the Screening visit (V1). This includes, paracetamol, tramadol, opioid-containing preparations, gabapentin, and pregabalin (other preparations may be considered on a case-by-case basis) 23. For 14 days prior to first dose of study treatment(s) treatment, taking any agent with high risk to prolong the QTc interval or to cause Torsades de Pointes (TdP) 24. Corticosteroid injections before Screening (V1): Intra-articular into the target joint within 3 months Intra-articular into any site other than the target joint within 1 month Intra-muscular within 3 months 25
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): •WOMAC Pain Score change from baseline (Day 0) to End of Treatment (Day 42);Timepoint(s) of evaluation of this end point: Day 42;Main Objective: •To assess the effect of PRX167700 treatment, on a background of stable oral NSAID therapy, on knee pain, in participants with moderate to severe pain caused by OA; Secondary Objective: - To assess the safety of PRX167700 when used in combination with oral NSAIDs - To assess additional measures of efficacy at Day 42 for PRX167700 when used in combination with oral NSAIDs for 6 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Incidence and severity of treatment emergent adverse events (TEAEs) throughout the dosing period •Incidence of TEAEs leading to withdrawal •Change in physical examination findings throughout the dosing period •Incidence of clinically significant changes on triplicate 12 lead electrocardiograms (ECGs) throughout the dosing period •Incidence and severity of treatment emergent changes in laboratory values •Change from Baseline in vital signs throughout the dosing period •Change from Baseline to Day 42 in the WOMAC Total Score •Change from Baseline to Day 42 in the WOMAC Stiffness Score •Change from Baseline to Day 42 in the WOMAC Function Score •Change from Baseline to Day 42 in the Patient Global Assessment (PGA) •Clinical Global Impression of Change (CGI C) at Day 42 •Proportion of participants with a response at Day 42 as defined by the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trial Response Criteria Initiative (OMERACT OARSI) Response Criteria •Proportion of participants with a reduction in the WOMAC Pain Score of = 50% at Day 42 •Withdrawal for lack of efficacy •Rescue medication use ;Timepoint(s) of evaluation of this end point: Day 7, 14, 28, 35 and 42 | — |
Countries
Czech Republic, Hungary, Poland, Spain, United Kingdom
Contacts
Public ContactClinical Trial Information
Proximagen Ltd.
Outcome results
None listed