Osteoarthritis of the knee MedDRA version: 21.1 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Code: LEVI-04
Pharmaceutical Form: Solution for infusion
Current Sponsor code: LEVI-04
Other descriptive name: LEVI-04
Concentration unit: g/ml gram(s)/millilitre
Concentration type: equal
Con
Sponsors
Levicept Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed Informed Consent form (ICF). 2. Male or female participants between =40 and =80 years of age. 3. BMI =40 kg/m2. 4. The ability to utilize the eDiary device provided by study sites. 5. History of knee pain on most days for at least 3 months prior to Screening 6. Confirmation of OA of the knee a. Radiographs of both knees with a Posterior-Anterior, Fixed-flexion view taken during the Screening Period. b. American College of Rheumatology (ACR) clinical and radiographic diagnostic criteria. 7. Evidence of knee OA with a KL grade =2, determined through central reading. 8. Target Knee must have a score of =20 out of 50 on the WOMAC pain subscale during Screening and at Randomization 9. The Baseline (NRS) Pain score will be derived from the last seven days of the Diary Run-In Period and must meet following criteria: a. Completion of Average Daily (NRS) Pain score on at least 6 of the 7 days. b. Mean Average Daily (NRS) Pain score must be =4.0 and =9.0 c. Mean Average Daily (NRS) Pain variability must be =1.5 10. If female, not of childbearing potential defined as post-menopausal for at least 1 year, or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or practicing an agreed upon highly effective method of birth control throughout the study period. 11. If male and sexually active with partner of childbearing potential, willing to agree to practice a highly effective method of contraception from Visit 2 and at least 3 months after Visit 11 (week 20). 12. Willing to withdraw from any medication for Osteoarthritis including, but not limited to, Opioids (including semisynthetic opioids), Non-Steroidal Anti-inflammatories (NSAIDs), COX-2 inhibitors, Topical medication, and Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs e.g Duloxetine). 13. Participant agrees to take only the allowed Rescue Medications from the start of the Diary Run-In Period through study completion (maximum 4000 mg paracetamol per day). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 313 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 207
Exclusion criteria
Exclusion criteria: 1. Presence of OA of other major joints (including nontarget knee) that could interfere with assessment of pain due to OA of the target knee, in the opinion of the investigator. 2. Current comorbid condition, other than OA, affecting target knee or systemic illness known to be significantly associated with arthritis or joint pathology affecting any joint, including endocrinopathies or autoimmune disease with significant joint involvement (e.g.,Rheumatoid Arthritis); Seronegative Spondyloarthropathies (e.g. Ankylosing Spondylitis, Psoriasis arthritis, Reactive arthritis) 3. Pathological conditions significantly affecting joint and bone health, in the opinion of the Investigator should be excluded (including following findings on x-rays and/or MRI): known presence of Rapidly Progressive Osteoarthritis, osteonecrosis (including avascular necrosis), subchondral insufficiency fractures (major joint), fractures or stress reactions with radiographic signs of ongoing healing processes (including osteoporotic and pathological fractures) (major joint), excessive malalignment of the knee (anatomical axis angle greater than 10 degrees) (Target knee only), complete tear of the posterior meniscal root (either knee), large or extensive subchondral cysts (either knee), anserine or patellar bursitis (Target knee only), significant articular bone loss, articular bone fragmentation or collapse, primary or metastatic tumor, joint infection, paget's disease, osteochondritis dissecans 4. Hip dislocation and congenital hip dysplasia with degenerative joint disease should be excluded 5. History of gout, or pseudogout, unless on hypouricemic therapy (including allopurinol) and no episodes within the last 12 months 6. Presence of neuropathic pain deemed likely to interfere with trial endpoints, complex regional pain syndrome, or chronic widespread pain syndromes e.g., fibromyalgia 7. History of significant trauma or surgery (excluding injection therapies and arthroscopy) to a knee, hip, or shoulder within the previous 1 year or previous target knee alloplasty 8. Planned major surgery or other major invasive procedures while participating in the study 9. Surgery or stent placement for coronary artery disease in the six months prior to screening 10. Nondiagnostic arthroscopy performed on the target knee joint within 180 days prior to Screening; or diagnostic arthroscopy performed on the target knee joint within 90 days prior to Screening 11. Intraarticular injection therapies to the target knee joint within 12 weeks prior to Screening, or to any non-target major joint within 6 weeks prior to Screening 12. Participants likely to be deemed unfit for joint replacement surgery due to concomitant illness, in the investigator opinion 13. Opioid use, including Tramadol, of 4 or more instances per week over the month prior to Screening 14. Known history of hypersensitivity to monoclonal antibodies 15. Presence of any medical condition or unstable health status that, in the judgment of the investigator, might adversely impact the safety of the participant or efficacy results of the trial 16. Medical history and/or clinical findings (including ECG) of cardiac disease that in the opinion of the investigator are considered of clinical significance, including but not limited to established ischemic heart disease, peripheral arterial disease and /or cerebrovascular disease (unstable angina, myocardial infarction, cardiovascular thrombotic events, transient ischemic attacks,
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of LEVI-04 (multiple doses) compared to placebo in reducing pain due to knee OA.;Secondary Objective: 1) To evaluate the efficacy of LEVI-04 (multiple doses) compared to placebo in improving physical function. 2) To evaluate the efficacy of LEVI-04 (multiple doses) compared to placebo in improving joint stiffness. 3) To evaluate the efficacy of LEVI-04 (multiple doses) compared to placebo in Patient Global Assessment (PGA). 4) To evaluate the proportion of responders based on various levels of reduced pain in participants receiving LEVI-04 (multiple doses) compared to placebo. 5) To evaluate rescue medication use in the LEVI-04 group (multiple doses) compared to placebo.;Primary end point(s): Change in WOMAC Pain subscale from Randomization (Visit 3) to Visit 10 (week 17);Timepoint(s) of evaluation of this end point: Week 17 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Change in WOMAC Pain subscale from Randomization (Visit 3) to Visit 6 (week 5). 2) Change in WOMAC Physical function subscale from Randomization (Visit 3) to Visit 6 (week 5) and Visit 10 (week 17). 3) Change in WOMAC Stiffness subscale from Randomization (Visit 3) to Visit 6 (week 5) and Visit 10 (week 17). 4) Change in StEPP from Randomization (Visit 3) to Visit 6 (week 5) and Visit 10 (week 17). 5) Change in PGA from Visit 6 (week 5) to Visit 10 (week 17). 6) Proportion of participants achieving 30% and 50% reduction in WOMAC Pain subscale at week 5 and week 17 using a cumulative distribution function. 7) Rescue Medication usage during the trial. 8) Change in average weekly NRS score from Randomization (Visit 3) to Visit 6 (week 5) and Visit 10 (week 17). 9) Area under the curve of Average Daily NRS pain from Randomization (Visit 3) to Visit 11 (week 20).;Timepoint(s) of evaluation of this end point: 1) From rand. to week 5. 2) From rand. to week 5 and week 17. 3) From rand. to week 5 and week 17. 4) From rand. to week 5 and week 17. 5) From week 5 to week 17. 6) Week 5 and week 17. 7) End of trial. 8) From rand. to week 5 and week 17. 9) From rand. to week 20. | — |
Countries
Czechia, Czech Republic, Denmark, Hong Kong, Moldova, Republic of, Poland
Contacts
Public ContactRegulatory Affairs
NBCD A/S
Outcome results
None listed