Clinical trial NCT03755934: Efficacy and Safety of MEDI7352 in Participants With Painful Diabetic Neuropathy
Official title: A Randomised, Double-Blind, Placebo-Controlled, Dose-Response Study of the Efficacy and Safety of MEDI7352 in Subjects With Painful Diabetic Neuropathy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Painful Diabetic Neuropathy
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-11-28
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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%).

Primary outcomes:
measure: Change From Baseline in Weekly Average of Average Daily Pain Score to Week 12
timeFrame: Baseline (Day -7 to Day -1, inclusive) through Week 12
Secondary outcomes:
measure: Change From Baseline in Weekly Average of Average Daily Pain Score
timeFrame: Baseline (Day -7 to Day -1, inclusive), Weeks 2, 4, 6, 8, 10, and 18
measure: Percentage of Participants With >= 30% and >= 50% Reductions in Weekly Average of Average Daily Pain Score
timeFrame: Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up)
measure: Change From Baseline in Galer Neuropathic Pain Scale (NPS)
timeFrame: Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up)
measure: Change From Baseline in Daily Sleep Interference Scale (DSIS)
timeFrame: Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up)
measure: Percentage of Participants With 'Improved', 'Much Improved', or 'Very Much Improved' Status in Patient Global Impression of Change (PGIC)
timeFrame: Baseline (Day -7 to Day -1, inclusive), Weeks 4, 8, 12, and 18 (follow-up)
measure: Change From Baseline in 36-item Short-Form Health Survey (SF-36)
timeFrame: Baseline (Day -7 to Day -1, inclusive) and Week 12
measure: Percentage of Participants Taking Any Rescue Medication
timeFrame: Baseline (Day -7 to Day -1, inclusive) through Week 12
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 through 20.42 weeks (maximum observed duration)
measure: Number of Participants With Abnormal Vital Signs Reported as TEAEs
timeFrame: Day 1 through 20.42 weeks (maximum observed duration)
measure: Number of Participants With Clinically Significant Abnormal Electrocardiograms (ECGs)
timeFrame: Day 1 through 20.42 weeks (maximum observed duration)
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
timeFrame: Day 1 through 20.42 weeks (maximum observed duration)
measure: Number of Participants With Clinically Significant Findings in Physical Examination Reported as TEAEs
timeFrame: Day 1 through 20.42 weeks (maximum observed duration)
measure: Number of Participants With Clinically Significant Findings in Neurological Examination
timeFrame: Day 1 through 20.42 weeks (maximum observed duration)
measure: Number of Participants With Abnormal Dorsiflexion Strength
timeFrame: Day 1 through 20.42 weeks (maximum observed duration)
measure: Number of Participants With Abnormal Deep Tendon Reflex (Knee and Ankle)
timeFrame: Day 1 through 20.42 weeks (maximum observed duration)
measure: Change From Baseline in Total Neuropathy Score-Nurse (TNSn)
timeFrame: Baseline (Day -45 to -1), pre-dose on Day 1, Weeks 2, 4, 6, 8, 10, 12, and 18/early termination
measure: Number of Participants With Investigator Reported Significant Changes From Baseline in Motor and Sensory Nerve Conduction
timeFrame: Day 1 through 20.42 weeks (maximum observed duration)
measure: Number of Participants With at Least One Concomitant Medication
timeFrame: Day 1 through 20.42 weeks (maximum observed duration)
measure: Number of Participants With Injection Site Reaction
timeFrame: Day 1 through 20.42 weeks (maximum observed duration)
measure: Number of Participants With Infusion Reaction
timeFrame: Day 1 through 20.42 weeks (maximum observed duration)
measure: Serum Total Nerve Growth Factor (NGF) Concentrations
timeFrame: Day 1 (pre-dose; baseline), Weeks 2, 4, 6, 8, 10 (Day 70; pre-dose, immediately before end of infusion, 8 hours and 24 hours post Day 70 infusion [Day 71]), 11, and 12 (approximately same time of day as Week 10 infusion)
measure: Number of Participants With Positive Anti-Drug Antibodies (ADA) to MEDI7352
timeFrame: Pre-dose at baseline (Day -45 to -1) and Study Weeks 2, 4, 8, 10, 12, and 18 (follow-up)
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Research Site
city: Balatonfüred
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Sochaczew
country: Poland
facility: Research Site
city: Toruń
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wrocław
country: Poland
facility: Research Site
city: Bucuresti
country: Romania
facility: Research Site
city: Calarasi
country: Romania
facility: Research Site
city: Craiova
country: Romania
facility: Research Site
city: Galati
country: Romania
facility: Research Site
city: Targu-Mures
country: Romania
facility: Research Site
city: Barnsley
country: United Kingdom
facility: Research Site
city: Blackpool
country: United Kingdom
facility: Research Site
city: Cannock
country: United Kingdom
facility: Research Site
city: Cardiff
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Prescot
country: United Kingdom
facility: Research Site
city: Stockton-on-Tees
country: United Kingdom
facility: Research Site
Study officials:
References: