Efficacy and Safety of MEDI7352 in Participants With Painful Diabetic Neuropathy

Change from baseline to Weeks 2, 4, 6, 8, 10, and 18 in weekly average of average daily pain score is reported. Participants assessed their perceived daily average neuropathic pain over the previous 24 hours using an 11-point NRS, with 0 representing no pain and 10 representing the worst pain imaginable. Participants were instructed to assess their average daily pain at approximately the same time every morning, and to record the response in a subject diary (ePRO).

Percentage of participants with >= 30% and >= 50% decrease in weekly average of average daily pain score from baseline is reported. Participants assessed their perceived daily average neuropathic pain over the previous 24 hours using an 11-point NRS, with 0 representing no pain and 10 representing the worst pain imaginable. Participants were instructed to assess their average daily pain at approximately the same time every morning, and to record the response in a subject diary (ePRO).

Participants were assessed for their neuropathic pain using the Galer NPS, which included 2 descriptors of pain, including intensity and unpleasantness, and 8 descriptors that assessed specific qualities of neuropathic pain: sharp, hot, dull, cold, sensitive, itchy, deep, and surface pain. Each of these 10 dimensions had a 0 to 10 NRS in which 0 is equal to no pain and 10 equals most intense pain. Galer NPS total score (ranges from 0 to 100; with 0 and 100 representing the no and highest degree of neuropathic-like symptoms, respectively) is sum of pain intensity, pain unpleasantness, pain sharpness, pain hotness, pain dullness, pain coldness, pain sensitivity, pain itching, deep pain intensity, and surface pain intensity (all in an 11-point NRS). Change from baseline to Weeks 4, 8, 12, and 18 (follow-up) in Galer NPS total score is reported.

Participants were assessed for how their neuropathic pain interferes with their sleep using the DSIS. It has an 11 point Likert response scale (0-10) that asked participants to "select the number that best describes how much your pain has interfered with your sleep during the past 24 hours". Responses vary from 0 (did not interfere with sleep) to 10 (completely interfered with sleep-unable to sleep due to pain). The DSIS was completed by participants once a day (upon awakening) to accurately capture variability in sleep interference due to pain on a daily basis, thus minimizing recall bias. Change from baseline to Weeks 4, 8, 12, and 18 (follow-up) in DSIS is reported.

Participants rated their overall improvement in health status using the PGIC. The PGIC consisted of a 7-point scale where 1 = very much improved and 7 = very much worse. The participants were asked the following question: How would you rate your overall improvement with treatment during the clinical study?, where the response options included the following: Very Much Improved, Much Improved, Minimally Improved, No Change, Minimally Worse, Much Worse, and Very Much Worse.

Change from baseline to Week 12 in SF-36 is reported. The SF-36 assesses 8 health concepts: 1) limitations in physical activities because of health problems (physical functioning); 2) limitations in social activities because of physical or emotional problems (social functioning); 3) limitations in usual role activities because of physical health problems (role physical); 4) bodily pain; 5) general mental health; 6) limitations in usual role activities because of emotional problems (role emotional); 7) vitality; and 8) general health perceptions. The items use Likert-type scales with either 5 or 6 points, or 2 or 3 points. Higher SF-36 scores indicate a better state of health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

Percentage of participants taking any rescue medication are reported. Participants were asked to record all rescue medications they take for neuropathic pain in a paper diary.

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (body temperature, diastolic blood pressure, systolic blood pressure, heart [pulse] rate, and respiratory rate).

Number of participants with clinically significant abnormal ECGs are reported.

Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of hematology, clinical chemistry, coagulation, and urinalysis.

Number of participants with clinically significant findings in physical examination reported as TEAE are reported. A complete physical examination (excluding the genitourinary examination, unless warranted) was performed.

Number of participants with clinically significant findings in neurological examination is reported.

Number of participants with abnormal dorsiflexion strength is reported. Dorsiflexion strength is scored on 0-4 scale. The scale indicated 0 = normal power, 1 = mild weakness, 2 = moderate weakness, 3 = severe weakness, and 4 = paralysis.

Number of participants with abnormal deep tendon reflex are reported. Deep tendon reflex (knee and ankle) strength is scored on 0-4 scale. The scale indicated 0 = normal, 1 = ankle reflex reduced, 2 = ankle reflex absent, 3 = ankle reflex absent and knee reflex reduced, and 4 = all reflexes (both ankle and knee) absent. Participants within a specific row are not included in any other row in the data table below.

The TNSn, a semi-quantitative clinical assessment of peripheral nervous system function, was administered at baseline (Screening), Day 1, Weeks 2, 4, 6, 8, 10, 12 and Week 18/early termination. The TNSn provides for an assessment of motor symptom score, autonomic symptom score, pin sensibility score, and vibration sensibility score. Each neuropathy item is scored on a 0-4 scale. The scores are summed to obtain a total score ranging from 0 to 20. Higher total scores correlate with more severe neuropathy. Not all of the early terminated participants completed the 18 week assessment. Only 3 early terminated participants contributed data at the Week 18 assessment.

Motor and sensory nerve conduction studies were performed in relevant lower and upper limb nerves (sural, peroneal, median/ulnar, fibular, and tibial nerves) wherein amplitude, peak latency, conduction velocity, and duration of nerve action potentials were recorded.

Number of participants with at least one concomitant medication is reported. A concomitant medication is defined as any medication continuing or starting after first dose of study medication.

Number of participants with injection site reaction is reported.

Number of participants with infusion reaction is reported.

Serum concentrations of total NGF in ADA positive or negative participants are reported.

Number of participants with positive ADA to MEDI7352 are reported. Treatment-induced ADA positive is defined as ADA negative at baseline and positive at least 1 post-baseline assessment. Treatment-boosted ADA positive is defined as ADA positive at baseline with pre-existing titre boosted by 4-fold or greater during the study period. Persistent positive is defined as ADA negative at baseline and positive at least 2 post-baseline assessments (with >= 16 weeks between first and last positive) or ADA positive at last post-baseline assessment. Transiently positive is defined as ADA negative at baseline and at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.