Efficacy and Safety of MEDI7352 in Participants With Painful Diabetic Neuropathy

Phase 2TerminatedNCT03755934

AstraZeneca112 enrolled

Overview

This is a study investigating the effect of MEDI7352 on chronic pain in participants 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. Participants will randomly be assigned to double-blind treatment with one of 4 dose levels of MEDI7352 or placebo.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

112

Conditions

Painful Diabetic Neuropathy

Interventions

MEDI7352DRUG

Participants will receive IV infusion of MEDI7352 as stated in arm description.

PlaceboOTHER

Participants will receive IV infusion of placebo as stated in arm description.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Key Inclusion criteria: * Male, or postmenopausal or surgically sterile female, 18 to 80 years of age * Body mass index of ≤ 42 kg/m\^2. * Chronic painful diabetic neuropathy (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) numerical rating scale (NRS). * Willing and able to discontinue all non-steroidal anti-inflammatory drug (NSAID) or cyclooxygenase-2 (COX-2) analgesic therapy. * Currently be taking medication for the treatment of PDN. Participants 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 osteoarthritis (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 participants 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 participant's PDN pain, as judged by the investigator. * Haemoglobin A1C greater than 10.0% (\> 10.0%).

Locations (31)

Research Site

Gentofte Municipality, Denmark

Outcomes

Primary Outcomes

Change From Baseline in Weekly Average of Average Daily Pain Score to Week 12

Change from baseline to Week 12 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 numerical rating scale (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 (electronic patient-reported outcome \[ePRO\]).

Time frame: Baseline (Day -7 to Day -1, inclusive) through Week 12

Secondary Outcomes

Change From Baseline in Weekly Average of Average Daily Pain Score

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).

Time frame: Baseline (Day -7 to Day -1, inclusive), Weeks 2, 4, 6, 8, 10, and 18

Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score

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).

Time frame: Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up)

Change From Baseline in Galer Neuropathic Pain Scale (NPS)

Data from ClinicalTrials.gov

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Research Site

Balatonfüred, Hungary

Research Site

Budapest, Hungary

Research Site

Bydgoszcz, Poland

Research Site

Gdansk, Poland

Research Site

Katowice, Poland

Research Site

Katowice, Poland

Research Site

Krakow, Poland

Research Site

Lublin, Poland

Research Site

Lublin, Poland

...and 21 more locations

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.

Time frame: Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up)

Change From Baseline in Daily Sleep Interference Scale (DSIS)

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.

Time frame: Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up)

Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC)

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.

Time frame: Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up)

Change From Baseline in 36-item Short-Form Health Survey (SF-36)

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).

Time frame: Baseline (Day -7 to Day -1, inclusive) and Week 12

Percentage of Participants Taking Any Rescue Medication

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.

Time frame: Baseline (Day -7 to Day -1, inclusive) through Week 12

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

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.