Diabetic Peripheral Neuropathic PainPhase 2NCT04476108
Chronic Pain Master Protocol (CPMP): A Study of LY3016859 in Participants With Diabetic Peripheral Neuropathic Pain
A Phase 2 study testing LY3016859 in people with Diabetic Peripheral Neuropathic Pain, run by Eli Lilly and Company at 36 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diabetic Peripheral Neuropathic Pain
- What is being tested?
- LY3016859
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 125 participants
- Where
- 36 sitesin 2 countries
- Study dates
- 15 Jul 2020to 11 Nov 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
36 sites in 2 countries.
36 sites in 2 countries
United States35 sites
VIN-Julie Schwartzbard
Aventura, Florida, 33180
Great Lakes Research Group, Inc.
Bay City, Michigan, 48706
Northwest Clinical Research Center
Bellevue, Washington, 98007-4209
Simon Williamson Clinic
Birmingham, Alabama, 35211
Boston Clinical Trials
Boston, Massachusetts, 02131
Synexus - US
Chandler, Arizona, 85224
Synexus Clinical Research
Chicago, Illinois, 60602
Northwestern University
Chicago, Illinois, 60611
Synexus - Cincinnati
Cincinnati, Ohio, 45236
StudyMetrix Research
City of Saint Peters, Missouri, 63303
Rapid Medical Research
Cleveland, Ohio, 44122
Aventiv Research Inc
Columbus, Ohio, 43213
Clinical Research of South Florida
Coral Gables, Florida, 33134
Synexus - US
Dallas, Texas, 75234
Altoona Center For Clinical Research
Duncansville, Pennsylvania, 16635
Synexus Clinical Research - Glendale
Glendale, Arizona, 85306
PharmQuest
Greensboro, North Carolina, 27408
Irvine Clinical Research Center
Irvine, California, 92614
ActivMed Practices and Research
Methuen, Massachusetts, 01844
Suncoast Research Group
Miami, Florida, 33135
Synexus - US
Murray, Utah, 84123
Coastal Carolina Research Center
North Charleston, South Carolina, 29405
Renstar Medical Research
Ocala, Florida, 34470
Synexus - US
Omaha, Nebraska, 68144
Synexus - US
Orlando, Florida, 32806
Synexus - US
Pinellas Park, Florida, 33781
Martin E. Hale M.D., P.A.
Plantation, Florida, 33317
Rainier Clinical Research Center
Renton, Washington, 98057
Artemis Institute for Clinical Research
Riverside, California, 92503
Synexus - US
San Antonio, Texas, 78229
Artemis Institute for Clinical Research
San Diego, California, 92103
Synexus Clinical Research US, Inc - Orlando
The Villages, Florida, 32162
Cotton O'Neil Infusion Center
Topeka, Kansas, 66606
MedVadis Research Corporation
Waltham, Massachusetts, 02451
Clinical Research Center of Reading,LLC
Wyomissing, Pennsylvania, 19610
About this study
Official title: 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.
- Conditions
- Diabetic Peripheral Neuropathic Pain
- Being tested
- LY3016859, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY3016859Drug
Administered IV
PlaceboDrug
Administered IV
| Study group | Role | What they receive |
|---|---|---|
| 750 Mg-500 mg LY3016859 | Experimental | 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. Receives: Drug: LY3016859 |
| Placebo | Placebo comparator | Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, up to Week 8
Secondary outcomes (7)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, up to Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2020
- Study start15 Jul 2020
- Primary completion8 Jul 2021
- Study completion11 Nov 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetic Peripheral Neuropathic PainStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 125 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04476108
- Sponsor's protocol ID
- 17535
- Other IDs
- H0P-MC-NP01
- Status last verified
- Nov 2023
- First submitted
- 15 Jul 2020
- Last updated
- 14 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
James DE, Bailey J, van der Walt JS, Winkler J, Schoemaker R. Population Pharmacokinetics and Pharmacodynamics of Fepixnebart (LY3016859) and Epiregulin in Patients with Chronic Pain. Clin Pharmacokinet. 2025 May;64(5):757-767. doi: 10.1007/s40262-025-01506-3. Epub 2025 Apr 23.
PubMed 40266472
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Placebo-Controlled, Phase 2 Clinical Trial to Evaluate LY3016859 for the Treatment of Diabetic Peripheral Neuropathic Pain
- ClinicalTrials.gov ID
- NCT04476108
- Acronym / sponsor ID
- 17535
- Conditions
- Diabetic Peripheral Neuropathic Pain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 125 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- 15 Jul 2020 (actual)
- Primary completion
- 8 Jul 2021 (actual)
- Study completion
- 11 Nov 2021 (actual)
- First posted
- 17 Jul 2020 (actual)
- Results
- Posted 3 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 750 Mg-500 mg LY3016859 | Experimental | Drug: LY3016859Participants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg intravenous (IV) infusion for a total of 4 doses. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants received LY3016859 every 2 weeks with 750 mg as starting dose followed by 500 mg IV infusion for a total of 4 doses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LY3016859Administered IV | Drug | 750 Mg-500 mg LY3016859 |
| PlaceboAdministered IV | Drug | Placebo |
Primary outcome
Change From Baseline in Average Pain Intensity as Measured by the NRS
Time frame: Baseline, up to Week 8
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.
7 secondary outcomes
Change From Baseline in the Brief Pain Inventory-Short Form (BPI-SF) Total Interference Score
Time frame: Baseline, up to Week 8
Change From Baseline for Overall Improvement as Measured by Patient's Global Impression of Change
Time frame: Baseline, up to Week 8
Change From Baseline for Worst Pain Intensity as Measured by NRS
Time frame: Baseline, up to Week 8
Change From Baseline on the Visual Analog Scale (VAS) for Pain
Time frame: Baseline, up to Week 8
Change From Baseline Assessment to Endpoint on the Sleep Scale From the Medical Outcomes Study (MOS Sleep Scale)
Time frame: Baseline, up to Week 8
Total Amount of Rescue Medication Use as Measured by Average Dosage Per Week
Time frame: Baseline up to Week 8
Change From Baseline on the EuroQol-5D 5 Level Questionnaire (EQ-5D-5L) (United States)
Time frame: Baseline, up to Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40266472James DE, Bailey J, van der Walt JS, Winkler J, Schoemaker R. Population Pharmacokinetics and Pharmacodynamics of Fepixnebart (LY3016859) and Epiregulin in Patients with Chronic Pain. Clin Pharmacokinet. 2025 May;64(5):757-767. doi: 10.1007/s40262-025-01506-3. Epub 2025 Apr 23.
- A Study of LY3016859 in Participants With Diabetic Peripheral Neuropathic PainLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
36 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LY3016859 in people with Diabetic Peripheral Neuropathic Pain, run by Eli Lilly and Company at 36 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Average Pain Intensity as Measured by the NRS (time frame: Baseline, up to Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04476108, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2023.