A Study of the Efficacy and Safety of MEDI7352 in Subjects With Painful Osteoarthritis of the Knee

Study Overview
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Brief Summary
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This is a Phase 2b randomised, double-blind, placebo-controlled, dose-response study in subjects with painful osteoarthritis (OA) of the knee. The study will assess the safety and efficacy of multiple doses of MEDI7352 compared to placebo, as well as the pharmacokinetics, pharmacodynamics and immunogenicity of MEDI7352 in subjects with moderate to severe chronic pain persistent for 3 months or more not adequately controlled by standard of care treatments.

Official Title
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: A Randomised, Double-blind, Placebo-controlled, Dose-response Study of the Efficacy and Safety of MEDI7352 in Subjects With Painful Osteoarthritis of the Knee:

Conditions
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Painful Osteoarthritis of the Knee

Intervention / Treatment
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* Biological: MEDI7352
* Biological: MEDI7352
* Biological: MEDI7352
* Biological: MEDI7352
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must understand the nature of the study and must give signed and dated written informed consent prior to the initiation of any study procedures, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. For participants participating in the optional genetic research, a separate signed and dated optional genetic research ICF must be provided prior to collection of samples for optional genetic research that supports the Genomics Initiative. If a participant declines to participate in the genetic research, this will have no influence on the ability of a participant to participate in the study. The participant should be willing and able to understand and comply with all protocol-specified restrictions and procedures and be able to use an electronic patient-reported outcome (ePRO) device as judged by the investigator. The participant must be considered likely to comply with the study protocol and to have a high probability of completing the study, as judged by the investigator. The participant must be willing and able to discontinue all analgesic therapy with NSAID or COX-2 inhibitors from the start of the washout period until the end of the FU period. This includes over-the-counter (OTC) pain medications and topical analgesics that contain an NSAID or COX-2 inhibitor. Exclusion Criteria: Requires current treatment with another biologic therapeutic agent, DMARD, or other Immunosuppressants. Previously received any form of anti-NGF; received anti-TNFs including but not limited to golimumab, certolizumab, infliximab, adalimumab, etanercept, or rituximab within 12 months prior to screening, or other biological DMARDs (including but not limited to abatacept, tocilizumab, and tofacitinib), or other immunosuppressants within 6 months prior to screening (with the exception of inhaled or topical corticosteroids). Currently receiving strong opioids for any indication Participation in another clinical study with an IP or device within 60 days or 5 half-lives, whichever is longer, prior to screening Plasma donation within 28 days of screening or any blood donation or blood loss > 500 mL within 2 months of screening. Previous allogeneic bone marrow or stem cell transplant. Received nonleukocyte-depleted whole blood transfusion within 120 days of the genetic research sample collection, if participating in the optional genetic research. Involvement in the planning and/or conduct of the study.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a Phase IIb, multinational, multicentre, randomised, double-blind, placebo-controlled, dose-response study of MEDI7352 in participants 18 to 80 years of age (inclusive) with moderate-to-severe chronic pain of the knee. The study consists of a screening period of up to 45 days, a 12-week treatment period, and a 24-week follow-up (FU) period. Daily pain scores (as measured on an 11-point numerical rating scale [NRS]) recorded at the first screening visit and from Day -7 to Day -1 will be used be used to determine eligibility. Participants will be randomised to one of 4 doses of MEDI7352 or placebo. Each participant will receive 6 doses of MEDI7352 or placebo during the treatment period. After the end-of-treatment (EOT) visit at Week 12, participants will enter the FU period, which comprises 3 clinic visits (Weeks 18, 32, and 36) and 4 FU phone calls (Weeks 15, 21, 24, and 28). All participants who receive IP are expected to complete the FU period.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Dose A: MEDI7352 Q2W | Biological: MEDI7352<br>* Dose A: MEDI7352 Q2W<br>|
| Experimental: Cohort 2<br>Dose B: MEDI7352 Q2W | Biological: MEDI7352<br>* Dose B: MEDI7352 Q2W<br>|
| Experimental: Cohort 3<br>Dose C: MEDI7352 Q2W | Biological: MEDI7352<br>* Dose C: MEDI7352 Q2W<br>|
| Experimental: Cohort 4<br>Dose D: MEDI7352 Q2W | Biological: MEDI7352<br>* Dose D: MEDI7352 Q2W<br>|
| Placebo Comparator: Cohort 5:<br>Placebo to match MEDI7352 Q2W | Biological: Placebo<br>* Placebo to match MEDI7352 Q2W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numerical Rating Scale pain scores | Change in the weekly average of daily NRS pain scores from baseline to Week 12. Average daily pain scores in the target joint will be recorded from a scale of 0 = no pain to 10 = most severe pain imaginable over the previous 24 hours. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain subscale from | Change in the WOMAC pain subscale from baseline to Week 12. The WOMAC pain subscale consists of 5 questions assessing the participant's pain due to OA in the target knee. Each question is scored on an NRS scale from 0 to 10, and the WOMAC pain subscale score is calculated as the mean score from all 5 questions, where higher scores represent higher pain | 12 Weeks | 
| The Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical function | Change in the WOMAC physical function subscale from baseline to Week 12 The WOMAC physical function subscale consists of 17 questions assessing the participant's difficulty in performing activities of daily living due to OA in the target knee. Each question is scored on an NRS scale from 0 to 10, and the WOMAC pain subscale score is calculated as the mean score from all 17 questions, where higher scores represent worse function | 12 Weeks | 
| Physician Global Assesment (PGA of OA) | Change in the PGA of OA from baseline to Week 12. The PGA of OA is a 5-point scale used to assess symptoms and activity impairment due to OA of the knee. Participants are asked to identify a number from 1 = very good (asymptomatic and no limitation to normal activities) to 5 = very poor (very severe symptoms which are intolerable and inability to carry out all normal activities). | 12 Weeks | 
| ADA titre | Serum concentration of ADA titre | 12 weeks | 
| Adverse Events | Number of Participants with adverse events and serious adverse events | Through study completion, an average of 10 months | 
| Anti-drug Antibodies (ADA) | Presence of ADA to MEDI7352 | through study completion, an average of 10 months | 
| concentration of MEDI7352 | Serum concentration of MEDI7352 | through study completion, an average of 10 months | 
| Percentage of responders as measured by the OARSI responder index using the OMERACT-OARSI | Percentage of responders as measured by the OARSI responder index using the OMERACT-OARS (Outcome Measures in Rheumatology Clinical Trials -OMERACT and Osteoarthritis Research Society International OARSI) at Weeks 2, 4, 8, 12, and 18 | Weeks 2, 4, 8, 12, and 18 | 
| Vital Signs (Blood Pressure) in mmHg | Change from baseline supine and standing blood pressure in all participants | Through study completion, an average of 10 months | 
| Vital Signs (Heart Rate) in beats per minute | Change from baseline heart rate in all participants | Through study completion, an average of 10 months | 
| Vital Signs (Respiratory Rate) in breaths per minute | Change from baseline respiratory rate in all participants | Through study completion, an average of 10 months | 
| Vital Signs (Temperature) in °C | Change from baseline temperature measurements in all participants | Through study completion, an average of 10 months | 
| Clinical laboratory assessments | Number of Participants with abnormal laboratory values | Through study completion, an average of 10 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis