Efficacy and Safety of MEDI7352 in Subjects With Painful Diabetic Neuropathy

A Randomised, Double-Blind, Placebo-Controlled, Dose-Response Study of the Efficacy and Safety of MEDI7352 in Subjects With Painful Diabetic Neuropathy

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

Study Overview

• Status: Completed
• Conditions: Painful Diabetic Neuropathy
• Intervention / Treatment: Other: Placebo; Biological: MEDI7352

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Gentofte, Denmark, 2820
    • Research Site
• Hungary
  • Balatonfüred, Hungary, 8230
    • Research Site
  • Budapest, Hungary, 1036
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-065
    • Research Site
  • Gdańsk, Poland, 80-382
    • Research Site
  • Katowice, Poland, 40-040
    • Research Site
  • Katowice, Poland, 40-282
    • Research Site
  • Kraków, Poland, 30-534
    • Research Site
  • Lublin, Poland, 20-093
    • Research Site
  • Lublin, Poland, 20064
    • Research Site
  • Olsztyn, Poland, 10117
    • Research Site
  • Poznań, Poland, 60-702
    • Research Site
  • Sochaczew, Poland, 96-500
    • Research Site
  • Toruń, Poland, 87100
    • Research Site
  • Warszawa, Poland, 01-192
    • Research Site
  • Warszawa, Poland, 01144
    • Research Site
  • Wrocław, Poland, 53-413
    • Research Site
• Romania
  • Bucuresti, Romania, 011025
    • Research Site
  • Calarasi, Romania, 917080
    • Research Site
  • Craiova, Romania, 200505
    • Research Site
  • Galati, Romania, 800291
    • Research Site
  • Targu-Mures, Romania, 540142
    • Research Site
• United Kingdom
  • Barnsley, United Kingdom, S75 3DL
    • Research Site
  • Blackpool, United Kingdom, FY2 0JH
    • Research Site
  • Cannock, United Kingdom, WS11 0BN
    • Research Site
  • Cardiff, United Kingdom, CF14 4XW
    • Research Site
  • Leeds, United Kingdom, LS10 1DU
    • Research Site
  • London, United Kingdom, NW10 7EW
    • Research Site
  • Manchester, United Kingdom, M13 9NQ
    • Research Site
  • Prescot, United Kingdom, L34 1BH
    • Research Site
  • Stockton-on-Tees, United Kingdom, TS17 6EW
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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%).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo
Experimental: Dose Level 1; MEDI7352	Biological: MEDI7352; MEDI7352
Experimental: Dose Level 2; MEDI7352	Biological: MEDI7352; MEDI7352
Experimental: Dose Level 3; MEDI7352	Biological: MEDI7352; MEDI7352
Experimental: Dose Level 4; MEDI7352	Biological: MEDI7352; MEDI7352

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2018
• Primary Completion (Actual): June 29, 2023
• Study Completion (Actual): June 29, 2023

Study Registration Dates

• First Submitted: October 31, 2018
• First Submitted That Met QC Criteria: November 26, 2018
• First Posted (Actual): November 28, 2018

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Pain; Diabetic Neuropathies
• Other Study ID Numbers: D5680C00002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes