Chronic Pain Master Protocol (CPMP): A Study of LY3016859 in Participants With Diabetic Peripheral Neuropathic Pain

Randomized, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate LY3016859 for the Treatment of Diabetic Peripheral Neuropathic Pain

This study is being done to test the safety and efficacy of the study drug LY3016859 for the treatment of diabetic peripheral neuropathic pain. This trial is part of the chronic pain master protocol H0P-MC-CPMP (NCT05986292) which is a protocol to accelerate the development of new treatments for chronic pain.

Study Overview

• Status: Completed
• Conditions: Diabetic Peripheral Neuropathic Pain
• Intervention / Treatment: Drug: Placebo; Drug: LY3016859

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Latin Clinical Trial Center
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Simon Williamson Clinic
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Synexus - US
    • Glendale, Arizona, United States, 85306
      • Synexus Clinical Research - Glendale
  • California
    • Irvine, California, United States, 92614
      • Irvine Clinical Research Center
    • Riverside, California, United States, 92503
      • Artemis Institute for Clinical Research
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
  • Florida
    • Aventura, Florida, United States, 33180
      • VIN-Julie Schwartzbard
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida
    • Miami, Florida, United States, 33135
      • Suncoast Research Group
    • Ocala, Florida, United States, 34470
      • Renstar Medical Research
    • Orlando, Florida, United States, 32806
      • Synexus - US
    • Pinellas Park, Florida, United States, 33781
      • Synexus - US
    • Plantation, Florida, United States, 33317
      • Martin E. Hale M.D., P.A.
    • The Villages, Florida, United States, 32162
      • Synexus Clinical Research US, Inc - Orlando
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60602
      • Synexus Clinical Research
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Infusion Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices and Research
    • Waltham, Massachusetts, United States, 02451
      • MedVadis Research Corporation
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Great Lakes Research Group, Inc.
  • Missouri
    • Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research
  • Nebraska
    • Omaha, Nebraska, United States, 68144
      • Synexus - US
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Synexus - Cincinnati
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research
    • Columbus, Ohio, United States, 43213
      • Aventiv Research Inc
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
    • Wyomissing, Pennsylvania, United States, 19610
      • Clinical Research Center of Reading,LLC
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center
  • Texas
    • Dallas, Texas, United States, 75234
      • Synexus - US
    • San Antonio, Texas, United States, 78229
      • Synexus - US
  • Utah
    • Murray, Utah, United States, 84123
      • Synexus - US
  • Washington
    • Bellevue, Washington, United States, 98007-4209
      • Northwest Clinical Research Center
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Have a visual analog scale (VAS) pain value ≥40 and <95 during screening.
• Have a history of daily pain for at least 12 weeks based on participant report or medical history.
• Have a value of ≤30 on the pain catastrophizing scale.
• Have a body mass index <40 kilograms per meter squared (kg/m²) (inclusive).
• Are willing to maintain a consistent regimen of any ongoing nonpharmacologic pain-relieving therapies (for example, physical therapy) and will not start any new nonpharmacologic pain-relieving therapies during study participation.
• Are willing to discontinue all medications taken for chronic pain conditions for the duration of the study.
• Have daily symmetrical foot pain secondary to peripheral neuropathy present for at least 6 months and as diagnosed through use of the Michigan Neuropathy Screening Instrument Part B ≥3 (©University of Michigan).
• Have a history and current diagnosis of type 1 or type 2 diabetes mellitus.
• Have stable glycemic control as indicated by a glycated hemoglobin ≤11 at time of screening.
• Are men, or women able to abide by reproductive and contraceptive requirements.

Exclusion Criteria:

• Have second- or third-degree atrioventricular (AV) heart block or AV dissociation or history of ventricular tachycardia.
• Have had a procedure within the past 6 months intended to produce permanent sensory loss in the target area of interest (for example, ablation techniques).
• Have surgery planned during the study for any reason, related or not to the disease state under evaluation.
• Have, in the judgment of the investigator, an acute, serious, or unstable medical condition or a history or presence of any other medical illness that would preclude study participation.
• There is an inability to rule out other causative or confounding sources of pain in the primary condition under study.
• Have had cancer within 2 years of baseline, except for cutaneous basal cell or squamous cell carcinoma resolved by excision.
• Have a substance use disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders (5th edition; DSM-5; American Psychiatric Association).
• Have congenital QT prolongation or QT interval corrected for heart rate using Fridericia's formula (QTcF) interval measurement >450 milliseconds (msec) for male participants, >470 msec for female participants, or >480 msec for participants with bundle branch block.
• Have any clinically important abnormality at screening, as determined by investigator, in physical or neurological examination, vital signs, electrocardiogram (ECG), or clinical laboratory test results that could be detrimental to the participant or could compromise the study.
• Have a positive human immunodeficiency virus (HIV) test result at screening.
• Are, in the judgment of the investigator, actively suicidal and therefore deemed to be at significant risk for suicide.
• Have an intolerance to acetaminophen or paracetamol or any of its excipients.
• Have a history of alcohol, illicit drug, analgesic or narcotic use disorder within 2 years prior to screening.
• Have a current drug-induced neuropathy, for example, due to some types of chemotherapy, or other types of peripheral neuropathy.
• Have known hereditary motor, sensory or autonomic neuropathies.
• Have an estimated glomerular filtration rate (eGFR) of less than 70 milliliters/minute/1.73m² during screening.
• Have any clinically serious or unstable cardiovascular, musculoskeletal disorder, gastrointestinal, endocrinologic, hematologic, hepatic, metabolic, urologic, pulmonary, dermatologic, immunologic, or ophthalmologic disease within 3 months of baseline.
• Have megaloblastic anemia or combined degeneration of the spinal cord.
• Have received any antibodies against nerve growth factor (NGF), or antibodies against EGFR, or EGFR tyrosine kinase inhibitors.
• Have a history of allergic reactions to monoclonal antibodies, or clinically significant multiple or severe drug allergies, including but not limited to erythema multiforme major, linear immunoglobulin A dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis.
• Have a history or presence of uncontrolled asthma, eczema, significant atopy, significant hereditary angio-edema or common variable immune deficiency.
• Have fibromyalgia

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 750 Mg-500 mg LY3016859; Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg intravenous (IV) infusion for a total of 4 doses.	Drug: LY3016859; Administered IV
Placebo Comparator: Placebo; Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses.	Drug: Placebo; Administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Average Pain Intensity as Measured by the NRS	The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their average pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine. Posterior mean change from baseline, 95% credible interval (CrI) was derived using Bayesian mixed model repeated measures.	Baseline, up to Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Brief Pain Inventory-Short Form (BPI-SF) Total Interference Score	The BPI-SF is a numeric rating scale that assesses the severity of pain (severity scale), its impact on daily functioning (Interference scale), and other aspects of pain (for example, location of pain, relief from medications) in various disease states. BPI-SF score ranges from 0 = no pain to 10 = pain as bad as you can imagine. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.	Baseline, up to Week 8
Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change	Patients Global Impression of Change captured the participant's perspective of treatment apart from sub-aspects of the general improvement. This is a numeric scale from 1 to 7: 1 = very much better, and 7 = very much worse. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.	Baseline, up to Week 8
Change From Baseline for Worst Pain Intensity as Measured by NRS	The NRS was used during the preliminary data entry period and daily throughout the study to describe pain severity. Participants were asked to describe their worst pain over the past 24 hours, on a scale of 0 to 10: 0 = no pain, and 10 = pain as bad as you can imagine. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.	Baseline, up to Week 8
Change From Baseline on the Visual Analog Scale (VAS) for Pain	VAS was a graphic, single-item scale where participants were asked to describe their pain intensity over the past week, on a scale of 0 to 100: 0 = no pain, and 100 = worst imaginable pain. Participants completed the VAS by placing a line perpendicular to the VAS line at a point that described their pain intensity. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.	Baseline, up to Week 8
Change From Baseline Assessment to Endpoint on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale)	The MOS Sleep Scale consists of 12 questions addressing the past week. Participants reported how often each sleep symptom or problem was present on a 5-point categorical scale ranging from 'all of the time' to 'none of the time.' It includes 12 questions with the first question assessing how long it takes the subject to fall asleep. The second question asks how many hours each night the subject slept. The remaining 10 questions have a range of 6 responses from 1="all of the time" to 6="none of the time". MOS Sleep scale scores range from 0 (min) to 100 (max). The original survey items are converted to a 0 to 100 range (by Converting 1 to 0, 2 to 25, 3 to 50, 4 to 75, and 5 to 100). Higher scores represent worse outcomes. Posterior mean change from baseline, 95% CrI was derived using Bayesian longitudinal model.	Baseline, up to Week 8
Total Amount of Rescue Medication Use as Measured by Average Dosage Per Week	Total Amount of Rescue Medication Use as Measured by Average Dosage per Week. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.	Baseline up to Week 8
Change From Baseline on the EuroQol-5D 5 Level Questionnaire (EQ-5D-5L) (United States)	The EQ-5D-5L assessed quality of life based on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participant was asked to 'check the ONE box that best describes your health TODAY,' choosing from 5 options (no problems, slight problems, moderate problems, severe problems, extreme problems) provided under each dimension. The scores in the 5 dimensions were summarized into a health state index score. The health state index value is a single value on a scale from less than 0 to 1 (negative values are valued as worse than death) with higher scores indicating better health: 0 = a health state equivalent to death, and 1 = perfect health. Posterior mean change from baseline, 95% CrI was derived using Bayesian mixed model repeated measures.	Baseline, up to Week 8

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM -5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of LY3016859 in Participants With Diabetic Peripheral Neuropathic Pain

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2020
• Primary Completion (Actual): July 8, 2021
• Study Completion (Actual): November 11, 2021

Study Registration Dates

• First Submitted: July 15, 2020
• First Submitted That Met QC Criteria: July 15, 2020
• First Posted (Actual): July 17, 2020

Study Record Updates

• Last Update Posted (Estimated): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 10, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neuralgia; Diabetic Neuropathies
• Other Study ID Numbers: 17535; H0P-MC-NP01 (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No