A Study of MEDI7352 in Painful Osteoarthritis of the Knee

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, drug levels and effects on the body of MEDI7352, in subjects with painful osteoarthritis of the knee.

Detailed Description
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An interleaved SAD/MAD Study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of MEDI7352 in subjects with painful osteoarthritis of the knee.

Official Title
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A Randomised, Double-Blind, Placebo-Controlled, Single- and Multiple-Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MEDI7352 in Subjects With Painful Osteoarthritis of the Knee

Conditions
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Chronic Pain

Intervention / Treatment
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* Biological: MEDI7352 for IV infusion
* Biological: Placebo for IV infusion
* Biological: MEDI7352 for Subcutaneous Injection
* Biological: Placebo for Subcutaneous Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects with painful osteoarthritis (OA) of the knee. Female subjects must be postmenopausal or surgically sterile. Body weight between 50kg and 145kg Willing and able to comply with the requirements of the protocol Exclusion Criteria: Current treatment with another biologic therapeutic agent Current of historical diagnosis of RA Current diagnosis of an immunological condition that is associated with another form of arthritis in addition to OA, including traumatic arthritis or a seronegative spondyloarthropathy At risk of destructive arthropathy, including Rapidly Progressive Osteoarthritis (RPOA), osteonecrosis, spontaneous osteonecrosis of the knee, subchondral insufficiency fractures, hip dislocation and pathological fracture Presence of clinically significant neuropathy or other clinically significant disorder involving abnormal peripheral sensation. Current serious or unstable clinically important illness.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI7352 IV<br>Up to 11 cohorts of subjects are planned to be dosed by IV infusion, with single and multiple ascending doses. | Biological: MEDI7352 for IV infusion<br>* MEDI7352 for IV infusion<br>|
| Placebo Comparator: IV Placebo<br>Up to 11 cohorts of subjects are planned to be dosed by IV infusion, with single and multiple ascending doses. | Biological: Placebo for IV infusion<br>* IV Placebo infusion<br>|
| Experimental: MEDI7352 Subcutaneous Injection<br>1 cohort of subjects is planned to be dosed by subcutaneous injection, one single ascending dose cohort. | Biological: MEDI7352 for Subcutaneous Injection<br>* MEDI7352 for subcutaneous injection<br>|
| Placebo Comparator: Subcutaneous Placebo<br>1 cohort of subjects is planned to be dosed by subcutaneous injection, one single ascending dose cohort. | Biological: Placebo for Subcutaneous Injection<br>* Subcutaneous Placebo Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352 | Adverse events, serious adverse events, | All visits from screening up to 56 days post single dose/84 days post multiple dose | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352 | Clinical laboratory assessments (serum chemistry, hematology, urinalysis) | All visits from screening up to 56 days post single dose/84 days post multiple dose | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352 | 12 Lead electrocardiogram (including QTc, QRS, PR intervals and ventricular rate) | All visits from screening up to 56 days post single dose/84 days post multiple dose | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352 | Vital signs (systolic and diastolic BP), heart rate | All visits from screening up to 56 days post single dose/84 days post multiple dose | 
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability of MEDI7352 | MRI | At screening and at follow up visit. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma drug concentration versus time curves for MEDI7352 | Area under the plasma drug concentration versus time curves from zero to infinity and to last observation (AUC 0-inf; AUC 0-t). | All visits from screening up to 56 days post single dose/84 days post multiple dose | 
| Maximum observed plasma drug concentration (Cmax) of MEDI7352 | Maximum observed plasma drug concentration (Cmax). | All visits from screening up to 56 days post single dose/84 days post multiple dose | 
| Time to maximum observed plasma drug concentration (Tmax) of MEDI7352 | Time to maximum observed plasma drug concentration (Tmax). | All visits from screening up to 56 days post single dose/84 days post multiple dose | 
| Terminal plasma elimination half-life (t1/2) of MEDI7352 | Terminal plasma elimination half-life (t1/2). | All visits from screening up to 56 days post single dose/84 days post multiple dose | 
| Apparent clearance (CL/F). | Apparent clearance (CL/F). | All visits from screening up to 56 days post single dose/84 days post multiple dose | 
| The presence of anti-drug antibodies (ADAs) to MEDI7352 | The incidence of anti-drug antibodies (a measure of the body's immune response to the drug). | All visits from screening up to 56 days post single dose/84 days post multiple dose | 
| Pain Numerical Rating Scale (NRS) | Numerical Rating Scale (NRS) | All visits from screening up to 56 days post single dose/84 days post multiple dose | 
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, stiffness subscale and function subscale. | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale, stiffness subscale and function subscale. | All visits from screening up to 56 days post single dose/84 days post multiple dose | 
| Patients' Global Impression of Change Scale (PGIC) | Patients' Global Impression of Change Scale (PGIC) | All visits from screening up to 56 days post single dose/84 days post multiple dose |