A Study to Evaluate Efficacy and Safety of GSK3858279 in Diabetic Peripheral Neuropathic Pain (NEPTUNE-17)

A Multicenter Randomized, Double-blind, Placebo-controlled Phase 2 Study to Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics and Target Engagement of GSK3858279 in Adult Participants With Chronic Diabetic Peripheral Neuropathic Pain (DPNP) /NEPTUNE-17

This is a multicenter randomized, double-blind, placebo-controlled phase 2 study to evaluate efficacy, safety, tolerability, pharmacokinetics, and target engagement of GSK3858279 in adult participants with chronic Diabetic Peripheral Neuropathic Pain (DPNP). The primary objective of the study is to assess the efficacy of GSK3858279 in participants with DPNP who have been unable to sufficiently manage their pain.

Study Overview

• Status: Terminated
• Conditions: Pain
• Intervention / Treatment: Drug: GSK3858279; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L 3W4
      • GSK Investigational Site
    • Vancouver, British Columbia, Canada, V5Y 3W2
      • GSK Investigational Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3C 0N2
      • GSK Investigational Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • GSK Investigational Site
    • Toronto, Ontario, Canada, L6S 0C6
      • GSK Investigational Site
• China
  • Beijing, China, 100032
    • GSK Investigational Site
  • Guangzhou, China, 510000
    • GSK Investigational Site
  • Harbin, China, 150001
    • GSK Investigational Site
  • Luoyang, China, 471003
    • GSK Investigational Site
  • Shanghai, China, 200032
    • GSK Investigational Site
  • Wuhan, China, 430030
    • GSK Investigational Site
  • Yueyang, China, 414000
    • GSK Investigational Site
• France
  • Corbeil-Essonnes, France, 91100
    • GSK Investigational Site
  • Mulhouse, France, 68100
    • GSK Investigational Site
• Germany
  • Bad Homburg, Germany, 61348
    • GSK Investigational Site
  • Mainz, Germany, 55128
    • GSK Investigational Site
  • Münster, Germany, 48145
    • GSK Investigational Site
  • Wallerfing, Germany, 94574
    • GSK Investigational Site
• Japan
  • Chiba, Japan, 260-0804
    • GSK Investigational Site
  • Fukuoka, Japan, 807-8556
    • GSK Investigational Site
  • Gunma, Japan, 370-3573
    • GSK Investigational Site
  • Hokkaido, Japan, 060-0061
    • GSK Investigational Site
  • Ibaraki, Japan, 300-0028
    • GSK Investigational Site
  • Kanagawa, Japan, 211-8533
    • GSK Investigational Site
  • Osaka, Japan, 565-0853
    • GSK Investigational Site
  • Tochigi, Japan, 321-0204
    • GSK Investigational Site
  • Tochigi, Japan, 321-0974
    • GSK Investigational Site
  • Tochigi, Japan, 322-8550
    • GSK Investigational Site
  • Tokyo, Japan, 103-0027
    • GSK Investigational Site
  • Tokyo, Japan, 104-0031
    • GSK Investigational Site
  • Tokyo, Japan, 143-0015
    • GSK Investigational Site
  • Tokyo, Japan, 160-0008
    • GSK Investigational Site
• Poland
  • Częstochowa, Poland, 42-217
    • GSK Investigational Site
  • Gdynia, Poland, 81-338
    • GSK Investigational Site
  • Katowice, Poland, 40-282
    • GSK Investigational Site
  • Katowice, Poland, 40-648
    • GSK Investigational Site
  • Katowice, Poland, 40-081
    • GSK Investigational Site
  • Katowice, Poland, 40-749
    • GSK Investigational Site
  • Skorzewo, Poland, 60-185
    • GSK Investigational Site
  • Sochaczew, Poland, 96-500
    • GSK Investigational Site
  • Warsaw, Poland, 02-117
    • GSK Investigational Site
• South Africa
  • Cape Town, South Africa, 7530
    • GSK Investigational Site
  • Johannesburg, South Africa, 2196
    • GSK Investigational Site
  • KwaDukuza, South Africa, 4450
    • GSK Investigational Site
  • Pretoria, South Africa, 0184
    • GSK Investigational Site
  • Somerset West, South Africa, 7130
    • GSK Investigational Site
• South Korea
  • Bucheon-si, South Korea, 422711
    • GSK Investigational Site
  • Daejeon, South Korea, 35233
    • GSK Investigational Site
  • Seoul, South Korea, 120-752
    • GSK Investigational Site
  • Seoul, South Korea, 136-705
    • GSK Investigational Site
  • Seoul, South Korea, 137-701
    • GSK Investigational Site
  • Seoul, South Korea
    • GSK Investigational Site
• Spain
  • A Coruña, Spain, 15006
    • GSK Investigational Site
  • Barcelona, Spain, 08023
    • GSK Investigational Site
  • Málaga, Spain, 29010
    • GSK Investigational Site
  • Palma de Mallorca, Spain, 07120
    • GSK Investigational Site
  • San SebastiAn de Los Rey, Spain, 28702
    • GSK Investigational Site
  • Torrevieja Alicante, Spain, 3186
    • GSK Investigational Site
• United Kingdom
  • Cannock, United Kingdom, WS11 0BN
    • GSK Investigational Site
  • Liverpool, United Kingdom, L9 7AL
    • GSK Investigational Site
  • Teesside, United Kingdom, TS17 6EW
    • GSK Investigational Site
  • West Yorkshire, United Kingdom, LS10 1DU
    • GSK Investigational Site
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • GSK Investigational Site
  • Arizona
    • Surprise, Arizona, United States, 85378
      • GSK Investigational Site
  • California
    • Cerritos, California, United States, 90703
      • GSK Investigational Site
    • Lomita, California, United States, 90717
      • GSK Investigational Site
  • Florida
    • Largo, Florida, United States, 33777
      • GSK Investigational Site
    • Miami, Florida, United States, 33135
      • GSK Investigational Site
    • Miami, Florida, United States, 33175
      • GSK Investigational Site
    • West Palm Beach, Florida, United States, 33401
      • GSK Investigational Site
  • Georgia
    • Decatur, Georgia, United States, 30030
      • GSK Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • GSK Investigational Site
  • Massachusetts
    • Waltham, Massachusetts, United States, 02451
      • GSK Investigational Site
  • New York
    • Williamsville, New York, United States, 14221
      • GSK Investigational Site
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • GSK Investigational Site
  • South Carolina
    • Lancaster, South Carolina, United States, 29720
      • GSK Investigational Site
  • Texas
    • Cypress, Texas, United States, 77429
      • GSK Investigational Site
    • DeSoto, Texas, United States, 75154
      • GSK Investigational Site
    • Houston, Texas, United States, 77030
      • GSK Investigational Site
    • McAllen, Texas, United States, 78501
      • GSK Investigational Site
  • Washington
    • Bellevue, Washington, United States, 98007
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must be 18-75 years of age inclusive, at the time of signing the informed consent.
• Type I or Type II diabetes with painful, distal, symmetrical, sensory motor neuropathy attributed to diabetes, of at least 6 months duration.
• A pain score ≥4 and less than or equal to (≤) 9 by the 11-point NRS (0-10) for average daily pain intensity over the past 24 hours at the screening visit.
• Body mass index (BMI) within the range 18-40 kilogram per meter square (kg/m^2) (inclusive)
• Capable of giving signed informed consent.

Exclusion Criteria:

• History or presence of cardiovascular, renal, gastrointestinal, lymphatic disorders which in the opinion of the investigator would interfere with the study procedures and/or assessments.
• Participant has current painful peripheral neuropathy due to a cause other than diabetes (e.g. pernicious anemia, hypothyroidism, post-herpetic neuralgia).
• History of significant allergies to monoclonal antibodies.
• Current enrolment or past participation in a clinical study of an investigational medicinal product intervention within the last 30 days or 5 half-lives (whichever is longer) of signing consent.
• Participants who are unlikely to comply with the protocol (e.g. uncooperative attitude, inability to return for subsequent visits, inability to complete the eDiary daily etc.) and/or otherwise considered by the Investigator to be unlikely to complete the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GSK3858279 60 mg; Participants received GSK3858279 SC injection 60 milligram (mg) once per week for 12 weeks.	Drug: GSK3858279; GSK3858279 was administered
Experimental: GSK3858279 360 mg; Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.	Drug: GSK3858279; GSK3858279 was administered
Placebo Comparator: Placebo; Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.	Drug: Placebo; Placebo was administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Weekly Average of Average Daily Pain Score at Week 12, Assessed on the Numeric Rating Scale (NRS)	The change from baseline (CFB) in the weekly average of the average daily pain score at Week 12 was assessed using Numeric Rating Scale (NRS). Participants recorded their average daily pain response daily using a Brief Pain Inventory Item 5. It is a single item designed for self-reporting average pain score for past 24 hours. Participants were asked to mark their average pain intensity daily, using the NRS, on an 11-point scale (0 = no pain, 10 = worst pain imaginable). The weekly average was computed as weekly average of the average daily scores (range: 0-10), where higher scores indicate more severe pain. A negative CFB indicates pain improvement. Baseline was defined as the average score over the 7 days before dosing (Day -7 to -1). Posterior mean CFB and the 95% credible interval were derived using a Bayesian mixed model repeated measures analysis. The data presented as "Mean" refers to the 'posterior mean' and "95% confidence interval" to '95% credible interval'.	Baseline (Day -7 to Day -1) and Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs), Serious AE (SAEs) and AEs of Special Interest (AESI)	Adverse events, SAEs, and AESIs were collected. An AE is any untoward medical occurrence in participant, temporally associated with use of study intervention, whether or not considered related to medicinal product. Any untoward event resulting in death, life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, medically important were categorized as SAE. AESIs of the study drug includes serious and opportunistic infections, tuberculosis (TB), serious hypersensitivity reactions and Injection site reactions.	Up to 27 weeks
Number of Participants With Greater Than Or Equal To (>=) Grade 3 Hematological/Clinical Chemistry Abnormalities According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)	The laboratory measurements included hematology and clinical chemistry. The parameters evaluated were Eosinophils, Hemoglobin, White blood cell, Lymphocyte count, Neutrophil count and Platelet count, Alanine aminotransferase, Alkaline phosphatase, Aspartate aminotransferase, Blood bilirubin, Hypercalcemia, Hypocalcemia, Cholesterol, Creatine Phosphokinase, Creatinine, Gamma Glutamyl Transferase (GGT), Hypoglycemia, Hyperkalemia, Hypernatremia and Hypertriglyceridemia. Worst case grade (G) increase from baseline grade was evaluated for all the laboratory tests that were gradable by National Cancer Institute Common Terminology Criteria (NCI CTCAE). Data is presented for only those parameters for which participants had worst case >= Grade 3 increase from Baseline.	Up to 27 weeks
Maximum Concentration (Cmax) of GSK3858279	Blood samples were collected for the determination of serum concentrations of GSK3858279 from which pharmacokinetic (PK) parameters were determined. Cmax was predicted from the population PK model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.	Pre-dose, Week 1, Week 4, Week 7, Week 8, Week 11, Week 12, Week 16, Week 20 and Week 27 post dose
Time to Maximum Concentration (Tmax) of GSK3858279	Blood samples were collected for the determination of serum concentrations of GSK3858279 from which PK parameters were determined. Tmax was predicted from the population PK model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.	Pre-dose, Week 1, Week 4, Week 7, Week 8, Week 11, Week 12, Week 16, Week 20 and Week 27 post dose
Trough Concentration at the End of the Dosing Interval (Ctau) of GSK3858279	Blood samples were collected for the determination of serum concentrations of GSK3858279 from which PK parameters were determined. Ctau is defined as the lowest concentration reached by a drug before the next dose is administered. Ctau was predicted from the population PK model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.	Pre-dose, Week 1, Week 4, Week 7, Week 8, Week 11, Week 12, Week 16, Week 20 and Week 27 post dose
Average Concentration Over a Dosing Interval (Cavg) of GSK3858279	Blood samples were collected for the determination of serum concentrations of GSK3858279 from which PK parameters were determined. Cavg is the average concentration over the dosing interval (weekly). Cavg was predicted from the population PK model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.	Pre-dose, Week 1, Week 4, Week 7, Week 8, Week 11, Week 12, Week 16, Week 20 and Week 27 post dose
Area Under the Time-Concentration Curve (AUC) Over the Dosing Interval (AUC[0-Tau]) of GSK3858279	Blood samples were collected for the determination of serum concentrations of GSK3858279 from which PK parameters were determined. AUC(0-tau) was predicted from the population model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis.	Pre-dose, Week 1, Week 4, Week 7, Week 8, Week 11, Week 12, Week 16, Week 20 and Week 27 post dose
Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time	The McGill pain questionnaire Short Form 2 is a 22-item questionnaire total score, which evaluated multi-dimensional pain over time. The questionnaire consists of 22 different descriptors of pain, and each item is rated based on a 0-10 pain intensity scale with 0 indicating no pain and 10 as worst possible pain. The total score was calculated as the mean of all item ratings. Higher scores indicate more severe pain. Baseline is defined as the last assessment prior to the first dose with a non-missing value, including those from unscheduled visits. Posterior mean change from baseline, 95 percent (%) credible interval (CI) was derived using Bayesian mixed model repeated measures. The data presented as 'Mean' refers to 'posterior mean' and '95% confidence interval' refers to '95% credible intervals'.	Baseline (Day1), Week 2, Week 4, Week 8 and Week 12
Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS	The change from baseline (CFB) in the weekly average of the average daily pain score at indicated time points was assessed using NRS. Participants recorded their average daily pain response daily using a Brief Pain Inventory Item 5. It is a single item designed for self-reporting average pain score for past 24 hours. Participants were asked to mark their average pain intensity daily, using the NRS, on an 11-point scale (0 = no pain, 10 = worst pain imaginable). The weekly average was computed as weekly average of the average daily scores (range: 0-10), where higher scores indicate more severe pain. A negative CFB indicates pain improvement. Baseline was defined as the average score over the 7 days before dosing (Day - 7 to -1). Posterior mean CFB and the 95% credible interval were derived using a Bayesian mixed model repeated measures analysis. The data presented as 'Mean' refers to the 'posterior mean' and '95% confidence interval' to the '95% credible interval'.	Baseline (Day -7 to Day -1), Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
Proportion of Participants With Greater Than or Equal To (>=) 30 Percentage (%) Reduction From Baseline in the Weekly Average of Average Daily Pain Intensity at Week 12, Assessed on the NRS	The proportion of participants who achieved >=30 percentage reduction from Baseline (responders) in the weekly average of the average daily pain score at Week 12 as measured by NRS is reported. Participants were instructed to assess their average daily pain daily, and to record the response in a Brief Pain Inventory item 5. It is a single item designed to capture information on the self- reported average pain score over the past 24 hours. Participants were asked to mark their pain- intensity daily, using the NRS, on an 11- point scale (0-10), with 0 = no pain, and 10 = worst pain imaginable. The weekly average was computed as weekly average of the average daily scores (range: 0-10), where higher scores indicate more severe pain. The data is presented for proportion of responders where 'Mean' refers to 'posterior mean proportion' and '95% confidence interval' refers to '95% credible interval'.	At Week 12
Proportion of Participants With Greater Than or Equal To >= 50 % Reduction From Baseline in the Weekly Average of Average Daily Pain Score at Week 12, Assessed on the NRS	The proportion of participants who achieved >=50 percentage reduction from Baseline (responders) in the weekly average of the average daily pain score at Week 12 as measured by NRS is reported. Participants were instructed to assess their average daily pain daily, and to record the response in a Brief Pain Inventory item 5. It is a single item designed to capture information on the self- reported average pain score over the past 24 hours. Participants were asked to mark their pain- intensity daily, using the NRS, on an 11- point scale (0-10), with 0 = no pain, and 10 = worst pain imaginable. The weekly average was computed as weekly average of the average daily scores (range: 0-10), where higher scores indicate more severe pain. The data is presented for proportion of responders where 'Mean' refers to 'posterior mean proportion' and '95% confidence interval' refers to '95% credible interval'.	At Week 12

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2023
• Primary Completion (Actual): October 14, 2024
• Study Completion (Actual): February 17, 2025

Study Registration Dates

• First Submitted: April 20, 2023
• First Submitted That Met QC Criteria: April 20, 2023
• First Posted (Actual): May 3, 2023

Study Record Updates

• Last Update Posted (Actual): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 10, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Diabetes; Safety; Efficacy; Pharmacokinetics; Neuropathic pain; Tolerability; GSK3858279; Diabetic Peripheral Neuropathic Pain (DPNP); 214221
• Additional Relevant MeSH Terms: Neurologic Manifestations; Endocrine System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Peripheral Nervous System Diseases; Glucose Metabolism Disorders; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Pain; Diabetes Mellitus; Neuralgia
• Other Study ID Numbers: 214221; 2022-502313-28-00 (Other Identifier: EU-CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; 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
• product manufactured in and exported from the U.S.: No