A study of MEDI7352 in painful osteoarthritis of the knee

Phase 1

Conditions: MedDRA version: 20.0Level: PTClassification code 10031161Term: OsteoarthritisSystem Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Painful osteoarthritis of the knee
Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Registration Number: EUCTR2020-003797-51-DK

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 300

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 opioids unless (a) opioids are contraindicated/not tolerated, (b) there is no access to opioids as per local standards of care, or (c) the patient is unwilling to take opioids.
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 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 150

Exclusion Criteria

Treatment with another biologic therapeutic agent, DMARD or other immunosuppressants
Previous treatment with any form of anti-NGF; received anti-TNFs in the past 12 months, or other biological DMARDs 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 fracture 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 anaphylactic/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, or 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, irrespective of severity or symptomatology, including asymptomatic, mild, or moderate within the last 3 months prior to screening
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 joint 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 intraarticular hyaluronic acid injection on nontarget 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-articular pl

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of MEDI7352 compared to placebo on chronic pain<br>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<br><br>To assess the PK and immunogenicity of MEDI7352 in participants with painful OA of the knee<br><br>To assess the safety and tolerability of MEDI7352 compared with placebo in participants with painful OA of the knee<br>;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 Outcome Measures

Name	Time	Method
Secondary end point(s): Efficacy:<br>Change in the WOMAC pain subscale from baseline to Week 12<br>Change in the WOMAC physical function subscale from baseline to Week 12<br>Change in the PGA of OA from baseline to Week 12<br><br>Serum concentration of MEDI7352<br>Presence of ADA to MEDI7352 <br>ADA titre<br><br>Safety and tolerability evaluated based on AEs, vital signs, and clinical<br>laboratory assessments;Timepoint(s) of evaluation of this end point: Efficacy: Week 12 (assessed at Weeks 1, 2, 4, 6, 8, 10, 12,18)<br><br>Safety and tolerability: Every study visit (Weeks 1, 2, 4, 6, 8, 10,11,12,15,18,21,24,28,32, 36)<br><br>Serum concentrations and ADA: Weeks 0, 1, 2, 4, 6, 8, 10, 11, 12, 18, 32

Related Trials