A Study to Evaluate Efficacy and Safety of GSK3858279 in Diabetic Peripheral Neuropathic Pain

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pain

Intervention / Treatment
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* Drug: GSK3858279
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK3858279 Dose 1<br>Participants will receive GSK3858279 dose 1. | Drug: GSK3858279<br>* GSK3858279 will be administered<br>|
| Experimental: GSK3858279 Dose 2<br>Participants will receive GSK3858279 dose 2. | Drug: GSK3858279<br>* GSK3858279 will be administered<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo. | Drug: Placebo<br>* Placebo will be administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the weekly average of average daily pain intensity at Week 12, assessed on the Numeric Rating Scale (NRS) | Brief Pain Inventory item 5 is a single item designed to capture information on the self-reported average pain intensity over the past 24 hours. Participants will be asked to mark their average pain intensity daily, using the NRS, on an 11-point scale (0-10), with 0 = no pain, and 10 = pain as bad as you can imagine. Daily scores for each participant will be averaged over 7 days to obtain a weekly score. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrences of adverse events (AEs), serious AE (SAEs), and AEs of special interest (AESI) | AEs, SAEs, and AESIs will be collected. 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) and TB reactivation, serious hypersensitivity reactions and Injection site reactions. | Up to 27 weeks | 
| Change from Baseline in Haematology Parameters: neutrophils, lymphocytes, monocytes, eosinophils, basophils, white blood cell (WBC), and platelet count (Giga cells per liter) |  | Baseline and up to Week 27 | 
| Change from Baseline in Haematology Parameters: Red blood cell (RBC) count, (Trillion cells per liter) |  | Baseline and up to Week 27 | 
| Change from baseline in haematology parameter: Haemoglobin (Hb) (Grams per liter) |  | Baseline and up to Week 27 | 
| Change from baseline in haematology parameter: Haematocrit (Proportion of red blood cells in blood) |  | Baseline and up to Week 27 | 
| Change from baseline in clinical chemistry parameters: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), Gamma-glutamyl transferase (GGT), and Alkaline Phosphatase (AP) (International units per liter) |  | Baseline and up to Week 27 | 
| Change from baseline in clinical chemistry parameter: Total bilirubin (Micromoles per liter) |  | Baseline and up to Week 27 | 
| 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 (NCICTCAE) | Hematological/clinical chemistry abnormalities summarized according to NCI CTCAE grade | Up to 27 weeks | 
| Maximum concentration (Cmax) of GSK3858279 | Cmax predicted from the D-E-R model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis. | At Week 12 | 
| The time required for GSK3858279 to reach Cmax (tmax) in the plasma | Tmax predicted from the D-E-R model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis. | At Week 12 | 
| Pre-dose (trough) concentration at the end of the dosing interval (Ctau) of GSK3858279 | Ctau predicted from the D-E-R model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis. | At Week 12 | 
| Average concentration over a dosing interval (Cavg) of GSK3858279 | GSK3859279 serum concentration time data collected at the indicated time points for PK analysis. | At Week 12 | 
| Area under the time-concentration curve (AUC) over the dosing interval (0-tau) (AUC[0-tau]) of GSK3858279 | AUC(0-tau) predicted from the D-E-R model fitted to GSK3859279 serum concentration time data collected at the indicated time points for PK analysis. | At Week 12 | 
| 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 evaluates multi-dimensional pain over time. The questionnaire consists of 22 descriptors that are rated on an intensity scale from 0 = none to 10 = worse possible | Baseline and up to Week 12 | 
| Change from baseline in the weekly average of. average daily pain intensity over time, assessed on the NRS | Brief Pain Inventory item 5 is a single item designed to capture information on the self-reported average pain intensity over the past 24 hours. Participants will be asked to mark. their pain intensity on a daily basis, using the NRS, on an 11-point scale (0-10), with 0 = no pain, and 10 = pain as bad as you can imagine. Daily scores for each participant will be averaged over 7 days to obtain a weekly score. | Baseline and up to Week 12 | 
| Number 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 | To capture information on the self-reported weekly average daily pain intensity. Participants will be asked to mark their pain-intensity daily, using the NRS, on an 11-point scale (0-10), with 0 = no pain, and 10 = pain as bad as you can imagine. Daily scores for each participant will be averaged over 7 days to obtain a weekly score. | At Week 12 | 
| Number of participants with greater than or equal to ≥ 50 % reduction from baseline in the weekly average of average daily pain intensity at Week 12, assessed on the NRS | To capture information on the self-reported weekly average daily pain intensity. Participants will be asked to mark their pain-intensity daily, using the NRS, on an 11-point scale (0-10), with 0 = no pain, and 10 = pain as bad as you can imagine. Daily scores for each participant will be averaged over 7 days to obtain a weekly score. | At Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Neuropathic pain, Diabetic Peripheral Neuropathic Pain (DPNP), 214221, GSK3858279, Efficacy, Safety, Pharmacokinetics, Tolerability