Painful osteoarthritis of the knee MedDRA version: 20.0 Level: PT Classification code 10031161 Term: Osteoarthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Product Code: MEDI7352
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: MEDI7352
Current Sponsor code: MEDI7352
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Males or postmenopausal or surgically sterile females, 18 to 80 years of age Men who are biologically capable of having children must use an adequate form of contraception during the treatment period and for 3 months and 20 days after the last IP administration BMI = 39 kg/m2 OA of one knee (ACR criteria) Radiological features consistent with a diagnosis of OA Pain in the moderate-to-severe range and pain most days in the past 3 months Pain must exceed pain experienced in other joints and pain from any concurrent medical conditions History of inadequate pain relief from past or ongoing treatment with paracetamol and oral NSAIDs/COX 2 inhibitors unless contraindicated/not tolerated and opoids unless (a) there is no access to opoids as per local standards of care, (b) there is no access to opoids as per local standards of care, or (c) the patient is unwilling to take opoids. Mean pain intensity score = 5 in the target knee (11 point NRS) Willingness/ability to discontinue analgesic therapy for OA with NSAID or COX 2 inhibitors during the entire study 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 175 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 175
Exclusion criteria
Exclusion criteria: Treatment with another biologic therapeutic agent, DMARD or other immunosuppressants Previous treatment with any form of anti-NGF; received anti-TNFs or other biological DMARD in the past 12 months, or other immunosuppressants in the past 6 months Treatment with strong opioids RA History of gout Comorbid condition known to be associated with other forms of arthritis or joint pathology other than OA RPOA, primary osteonecrosis, subchondral insufficiency fractures, avascular necrosis, osteoporotic fractures, hip dislocation, pathological fractures or stress facture or reaction Significant trauma to a knee, hip, or shoulder within the previous year Candidates unsuitable for joint replacement surgery Neuropathic pain or chronic primary pain syndromes eg fibromyalgia OA of other major joints that could interfere with assessment of pain Clinically significant neuropathy Wheelchair required for mobility History or current diagnosis of severe major depression, psychotic disorders, somatoform disorders, bipolar disorders. suicidal attempts, hospital admission for depression within the past 5 years or any other of psychiatric illness likely to confound drug effect, pain assessment or ability to complete the study Significant cardiovascular disease Significant or chronic lung disease Diabetes complicated with retinopathy or nephropathy; HBA1c > 8.5 Known or suspected systemic infection, including HIV, HBV, HCV or TB History of an opportunistic infection or residence in areas with endemic fungal infections History or evidence of demyelinating disorder or epilepsy History of anaphylatic/severe hypersensitivity reactions, history of hypersensitivity to immunisations or immunoglobulins and/or biological therapies, ongoing hypersensitivity reactions Lifetime history of haematopoietic malignancies, history of other specified cancers within 5 years, or diagnosis of cancer between screening and randomisation TIA in the last 6 months, stroke in the past 12 months History of substance abuse within 2 years Current active infection, chronic or persistent systemic infection or serious or severe localised or systemic infection within 3 months prior to screening or between screening and randomisation or history of any underlying condition that predisposes to infection Any history of severe COVID 19 infection, or any prior COVID-19 infection with unresolved sequelae. Any acute COVID-19 infection, including asymptomatic, mild, or moderate that is not resolved 1 month prior to randomisation Current serious or unstable clinically important illness, including respiratory, CV, GI, endocrinologic, immunologic, haematologic, or neurological or other major disease likely to deteriorate or affect safety or ability to complete the study; liver cirrhosis Family history of long QT syndrome History of intolerability or contraindications to paracetamol Surgery to a knee, hip or shoulder within 1 year; non-diagnostic arthroscopy on the target knee joint within 180 days; diagnostic arthroscopy on the target knee within 90 days Corticosteroid or intra-articular hyaluronic acid injection on target knee within 12 weeks or corticosteroid injection on a nontarget joint within 12 weeks, or intra-articular hyaluronic acid injection on non target joint within 6 weeks prior to screening; for multiple injections within the year total dose of corticosteroid > 180 mg of triamcinolone, methylprednisolone, or their equivalent Intra-artciular platelet-rich plasma treatment on the target jo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of MEDI7352 compared to placebo on chronic pain in participants with painful OA of the knee;Secondary Objective: To assess the efficacy of MEDI7352 compared to placebo on additional measures of efficacy in participants with painful OA of the knee To assess the PK and immunogenicity of MEDI7352 in participants with painful OA of the knee To assess the safety and tolerability of MEDI7352 compared with placebo in participants with painful OA of the knee ;Primary end point(s): Change in the weekly average of daily NRS pain scores from baseline to Week 12;Timepoint(s) of evaluation of this end point: Week 12 (NRS pain scores recorded daily) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: Change in the WOMAC pain subscale from baseline to Week 12 Change in the WOMAC physical function subscale from baseline to Week 12 Change in the PGA of OA from baseline to Week 12 Serum concentration of MEDI7352 Presence of ADA to MEDI7352 ADA titre Safety and tolerability evaluated based on AEs, vital signs, and clinical laboratory assessments;Timepoint(s) of evaluation of this end point: Efficacy: Week 12 (assessed at Weeks 1, 2, 4, 6, 8, 10, 12,18) Safety and tolerability: Every study visit (Weeks 1, 2, 4, 6, 8, 10,11,12,15,18,21,24,28,32,36) Serum concentrations and ADA: Weeks 0, 1, 2, 4, 6, 8, 10, 11, 12, 18, 32 | — |
Countries
Denmark, Estonia, Germany, Poland, South Africa, Spain, United Kingdom
Contacts
Public ContactInformation Desk
AstraZeneca
Outcome results
None listed