Efficacy and Safety of MEDI7352 in Subjects With Painful Diabetic Neuropathy

Study Overview
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Brief Summary
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This is a study investigating the effect of MEDI7352 on chronic pain in patients with painful diabetic neuropathy. The study incudes a screening period of up to 45 days and a 12-week treatment period during which MEDI7352 or placebo will be administered intravenously (IV) on 6 occasions, with each dose separated by 14 days. There will be a 6-week follow-up period. Subjects will randomly be assigned to double-blind treatment with one of 4 dose levels of MEDI7352 or placebo

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 Diabetic Neuropathy

Conditions
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Painful Diabetic Neuropathy

Intervention / Treatment
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* Biological: MEDI7352
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion criteria: Male, or postmenopausal or surgically sterile female, 18 to 80 years of age Body mass index of ≤42 kg/m2. Chronic PDN persistent for 6 months or longer, not adequately controlled by standard of care treatments. mean pain intensity score of ≥4, as measured on an 11-point (0-10) NRS willing and able to discontinue all NSAID or COX-2 analgesic therapy currently be taking medication for the treatment of PDN. Subjects should be taking at least one of the first-line medications (consistent with regional or local standard of care guidelines for PDN) Key Exclusion criteria: Presence of other clinically significant neuropathy (eg, hereditary neuropathy, inflammatory neuropathy) or other clinically significant disorder (eg, nerve compression injury) involving abnormal peripheral sensation, with an aetiology that is considered to be distinct from that of PDN, and that is likely to interfere with assessment of peripheral nerve function, as judged by the investigator. History of osteonecrosis, rapidly progressing OA, subchondral insufficiency fractures, neurogenic arthropathy, or analgesia-induced arthropathy. Diagnosis of clinically significant OA currently affecting a major joint in the upper extremity (shoulder, elbow, or wrist) or lower extremity (hip, knee, or ankle) or axial spine; or other degenerative disease affecting any joint in subjects for whom, in the opinion of the investigator, there is an identified risk of osteonecrosis, rapidly progressing OA, subchondral insufficiency fractures, neurogenic arthropathy, or analgesia-induced arthropathy. Chronic pain condition, other than PDN, that is likely to interfere with the evaluation of the subject's PDN pain, as judged by the investigator Haemoglobin A1C greater than 8.5% (>8.5%).

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Level 1<br>MEDI7352 | Biological: MEDI7352<br>* MEDI7352<br>|
| Experimental: Dose Level 2<br>MEDI7352 | Biological: MEDI7352<br>* MEDI7352<br>|
| Experimental: Dose Level 3<br>MEDI7352 | Biological: MEDI7352<br>* MEDI7352<br>|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* Placebo<br>|
| Experimental: Dose Level 4<br>MEDI7352 | Biological: MEDI7352<br>* MEDI7352<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the weekly average of the average daily pain scores | Change in the weekly average of the average daily pain scores from the baseline week to Week 12 of MEDI7352 compared to placebo, as measured on an 11-point (0-10) NRS. | from the baseline week to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the weekly average of the average daily pain scores | Change in the weekly average of the average daily pain score, as measured on an 11-point (0-10) NRS, from baseline to Weeks 2, 4, 6, 8, and 10 of treatment and the week before the follow-up visit (week 17). | Weeks 2, 4, 6, 8, and 10 of treatment and the week before the follow-up visit (week 17). | 
| Change in the weekly average of the average daily pain scores | Percentage of subjects who have achieved ≥30% and ≥50% reductions in the weekly average of the average daily pain score from baseline during Weeks 4, 8, and 12 of treatment and the week before follow-up (week 17). | from baseline during Weeks 4, 8, and 12 of treatment and the week before follow-up (week 17). | 
| Change in Galer Neuropathic Pain Scale (NPS) | Change in Galer Neuropathic Pain Scale (NPS) from baseline to Days 28, 56, and 84 of treatment and the follow-up visit (week 18). | from baseline to Days 28, 56, and 84 of treatment and the follow-up visit (week 18) | 
| Change in Daily Sleep Interference Scale (DSIS) | Change in Daily Sleep Interference Scale (DSIS) from baseline to Days 28, 56, and 84 of treatment and the follow-up visit (week 18). | from baseline to Days 28, 56, and 84 of treatment and the follow-up visit (week 18) | 
| Proportion of subjects who have 'improved', 'much improved,' or 'very much improved' relative to baseline on the Patient Global Impression of Change (PGIC) | Proportion of subjects who have 'improved', 'much improved,' or 'very much improved' relative to baseline on the Patient Global Impression of Change (PGIC) on Days 28, 56, and 84 of treatment and the follow-up visit (week 18). | on Days 28, 56, and 84 of treatment and the follow-up visit (week 18). | 
| Change in the 36-item Short-Form Health Survey (SF-36) | Change in the 36-item Short-Form Health Survey (SF-36) from baseline to Day 84 of treatment. | from baseline to Day 84 of treatment | 
| Change in the amount of rescue medication used (in terms of dosage/day) | Change in the amount of rescue medication used (in terms of dosage/day) from baseline to Week 12 of treatment. | from baseline to Week 12 of treatment | 
| incidence of AEs and SAEs |  | from baseline up to 18 weeks | 
| Area under the plasma concentration versus time curve of MEDI7352 |  | from baseline up to 18 weeks | 
| Peak Plasma Concentration (Cmax) of MEDI7352 |  | from baseline up to 18 weeks | 
| Summary of positive ADA against MEDI7352 |  | from baseline up to 18 weeks | 
| To characterise the dose-response relationship of MEDI7352 on chronic pain in subjects with PDN | Change in the weekly average of the average daily pain scores from the baseline week to Week 12, as measured on an 11-point (0-10) NRS, versus dose. | from baseline up to 12 weeks |