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
Overview
- Phase
- Phase 2
- Intervention
- GSK3858279
- Conditions
- Pain
- Sponsor
- GlaxoSmithKline
- Enrollment
- 147
- Locations
- 1
- Primary Endpoint
- Change From Baseline in the Weekly Average of Average Daily Pain Score at Week 12, Assessed on the Numeric Rating Scale (NRS)
- Status
- Terminated
- Last Updated
- 5 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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.
Arms & Interventions
GSK3858279 60 mg
Participants received GSK3858279 SC injection 60 milligram (mg) once per week for 12 weeks.
Intervention: GSK3858279
GSK3858279 360 mg
Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.
Intervention: GSK3858279
Placebo
Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline in the Weekly Average of Average Daily Pain Score at Week 12, Assessed on the Numeric Rating Scale (NRS)
Time Frame: Baseline (Day -7 to Day -1) and Week 12
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'.
Secondary Outcomes
- Number of Participants With Adverse Events (AEs), Serious AE (SAEs) and AEs of Special Interest (AESI)(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)(Up to 27 weeks)
- Maximum Concentration (Cmax) of GSK3858279(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(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(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(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(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(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(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(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(At Week 12)