Trial Outcomes & Findings for A Study to Evaluate Efficacy and Safety of GSK3858279 in Diabetic Peripheral Neuropathic Pain (NCT NCT05838755)

NCT ID: NCT05838755

Last Updated: 2025-11-21

Results Overview

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'.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 147 participants
• Primary outcome timeframe: Baseline (Day -7 to Day -1) and Week 12
• Results posted on: 2025-11-21

Participant Flow

A total of 147 participants were enrolled in the study, Out of which 144 participants were included in the full analysis set (FAS) population.

A total of 147 participants were enrolled in the study. Three participants were randomized but did not receive any study drug, hence were excluded from the FAS.

Participant milestones

Measure	Placebo Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.	GSK3858279 60 mg Participants received GSK3858279 SC injection 60 milligram (mg) once per week for 12 weeks.	GSK3858279 360 mg Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.
Overall Study STARTED	50	48	49
Overall Study Full Analysis Set	48	48	48
Overall Study COMPLETED	20	17	17
Overall Study NOT COMPLETED	30	31	32

Reasons for withdrawal

Measure	Placebo Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.	GSK3858279 60 mg Participants received GSK3858279 SC injection 60 milligram (mg) once per week for 12 weeks.	GSK3858279 360 mg Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.
Overall Study Adverse Event	1	0	0
Overall Study Lack of Efficacy	1	0	1
Overall Study Lost to Follow-up	0	1	4
Overall Study Withdrawal by Subject	0	2	0
Overall Study Study terminated by sponsor	26	27	26
Overall Study Randomized, not treated	2	0	1
Overall Study Pregnancy	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=48 Participants Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.	GSK3858279 60 mg n=48 Participants Participants received GSK3858279 SC injection 60 mg once per week for 12 weeks.	GSK3858279 360 mg n=48 Participants Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.	Total n=144 Participants Total of all reporting groups
Age, Continuous	61.3 YEARS STANDARD_DEVIATION 8.59 • n=68 Participants	60.1 YEARS STANDARD_DEVIATION 10.18 • n=76 Participants	60.2 YEARS STANDARD_DEVIATION 9.26 • n=48 Participants	60.5 YEARS STANDARD_DEVIATION 9.32 • n=33 Participants
Sex: Female, Male Female	21 Participants n=68 Participants	19 Participants n=76 Participants	22 Participants n=48 Participants	62 Participants n=33 Participants
Sex: Female, Male Male	27 Participants n=68 Participants	29 Participants n=76 Participants	26 Participants n=48 Participants	82 Participants n=33 Participants
Race/Ethnicity, Customized White	30 Participants n=68 Participants	24 Participants n=76 Participants	25 Participants n=48 Participants	79 Participants n=33 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=68 Participants	2 Participants n=76 Participants	0 Participants n=48 Participants	2 Participants n=33 Participants
Race/Ethnicity, Customized Asian	15 Participants n=68 Participants	12 Participants n=76 Participants	14 Participants n=48 Participants	41 Participants n=33 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=68 Participants	8 Participants n=76 Participants	9 Participants n=48 Participants	18 Participants n=33 Participants
Race/Ethnicity, Customized Mixed race	1 Participants n=68 Participants	1 Participants n=76 Participants	0 Participants n=48 Participants	2 Participants n=33 Participants
Race/Ethnicity, Customized Not reported	0 Participants n=68 Participants	1 Participants n=76 Participants	0 Participants n=48 Participants	1 Participants n=33 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=68 Participants	0 Participants n=76 Participants	0 Participants n=48 Participants	1 Participants n=33 Participants

PRIMARY outcome

Timeframe: Baseline (Day -7 to Day -1) and Week 12

Population: The analysis was performed on the Full Analysis Set population that included all randomized participants who received at least one dose of study intervention. Number of participants with analyzable outcome (measured outcome used in estimation or imputed outcome based on composite intercurrent event strategy) at the current time point were included in the Overall Number of Participants Analyzed field.

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'.

Outcome measures

Measure	Placebo n=33 Participants Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.	GSK3858279 60 mg n=32 Participants Participants received GSK3858279 SC injection 60 milligram (mg) once per week for 12 weeks.	GSK3858279 360 mg n=32 Participants Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.
Change From Baseline in the Weekly Average of Average Daily Pain Score at Week 12, Assessed on the Numeric Rating Scale (NRS)	-1.85 Scores on a Scale 95% Confidence Interval -2.44 • Interval -2.44 to -1.28	-2.50 Scores on a Scale 95% Confidence Interval -3.09 • Interval -3.09 to -1.91	-2.07 Scores on a Scale 95% Confidence Interval -2.67 • Interval -2.67 to -1.48

SECONDARY outcome

Timeframe: Up to 27 weeks

Population: This analysis was performed on Safety Set which included all participants who received at least 1 dose of study treatment.

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.

Outcome measures

Measure	Placebo n=48 Participants Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.	GSK3858279 60 mg n=48 Participants Participants received GSK3858279 SC injection 60 milligram (mg) once per week for 12 weeks.	GSK3858279 360 mg n=48 Participants Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.
Number of Participants With Adverse Events (AEs), Serious AE (SAEs) and AEs of Special Interest (AESI) Any AE	27 Participants	23 Participants	24 Participants
Number of Participants With Adverse Events (AEs), Serious AE (SAEs) and AEs of Special Interest (AESI) Any SAE	4 Participants	2 Participants	0 Participants
Number of Participants With Adverse Events (AEs), Serious AE (SAEs) and AEs of Special Interest (AESI) Any AESI	6 Participants	4 Participants	5 Participants

SECONDARY outcome

Timeframe: Up to 27 weeks

Population: This analysis was performed on Safety Set which included all participants who received at least 1 dose of study treatment. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. 'Number Analyzed' signifies participants evaluable for specified time points.

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.

Outcome measures

Measure	Placebo n=46 Participants Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.	GSK3858279 60 mg n=46 Participants Participants received GSK3858279 SC injection 60 milligram (mg) once per week for 12 weeks.	GSK3858279 360 mg n=46 Participants Participants received GSK3858279 SC injection 360 mg once per week for 12 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) >= Grade 3 increase in Hematological Abnormalities	0 Participants	0 Participants	0 Participants
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) Grade3 increase-Clinical Chemistry Abnormality,GGT	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Pre-dose, Week 1, Week 4, Week 7, Week 8, Week 11, Week 12, Week 16, Week 20 and Week 27 post dose

Population: This analysis was performed on Pharmacokinetic (PK) set which included all randomized participants in the Safety Population who had at least 1 dose of GSK3858279 and at least 1 non-missing PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values). Only those participants with data available at specified time points have been analyzed.

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.

Outcome measures

Measure	Placebo n=25 Participants Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.	GSK3858279 60 mg n=25 Participants Participants received GSK3858279 SC injection 60 milligram (mg) once per week for 12 weeks.	GSK3858279 360 mg Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.
Maximum Concentration (Cmax) of GSK3858279	2943.3 Nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 58 • Interval 58.0 to	17125.9 Nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 34 • Interval 34.0 to	—

SECONDARY outcome

Timeframe: Pre-dose, Week 1, Week 4, Week 7, Week 8, Week 11, Week 12, Week 16, Week 20 and Week 27 post dose

Population: The analysis was performed on Pharmacokinetic (PK) set which included all randomized participants in the Safety Population who had at least 1 dose of GSK3858279 and at least 1 non-missing PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values). Only those participants with data available at specified time points have been analyzed.

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.

Outcome measures

Measure	Placebo n=25 Participants Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.	GSK3858279 60 mg n=25 Participants Participants received GSK3858279 SC injection 60 milligram (mg) once per week for 12 weeks.	GSK3858279 360 mg Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.
Time to Maximum Concentration (Tmax) of GSK3858279	1.518 Day Full Range 0.64 • Interval 0.64 to 2.92	1.360 Day Full Range 0.47 • Interval 0.47 to 6.32	—

SECONDARY outcome

Timeframe: Pre-dose, Week 1, Week 4, Week 7, Week 8, Week 11, Week 12, Week 16, Week 20 and Week 27 post dose

Population: This analysis was performed on Pharmacokinetic (PK) set which included all randomized participants in the Safety Population who had at least 1 dose of GSK3858279 and at least 1 non-missing PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values). Only those participants with data available at specified time points have been analyzed.

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.

Outcome measures

Measure	Placebo n=25 Participants Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.	GSK3858279 60 mg n=25 Participants Participants received GSK3858279 SC injection 60 milligram (mg) once per week for 12 weeks.	GSK3858279 360 mg Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.
Trough Concentration at the End of the Dosing Interval (Ctau) of GSK3858279	1910.4 Nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 52 • Interval 52.0 to	9543.2 Nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 43 • Interval 43.0 to	—

SECONDARY outcome

Timeframe: Pre-dose, Week 1, Week 4, Week 7, Week 8, Week 11, Week 12, Week 16, Week 20 and Week 27 post dose

Population: This analysis was performed on Pharmacokinetic (PK) set which included all randomized participants in the Safety Population who had at least 1 dose of GSK3858279 and at least 1 non-missing PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values). Only those participants with data available at specified time points have been analyzed.

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.

Outcome measures

Measure	Placebo n=25 Participants Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.	GSK3858279 60 mg n=25 Participants Participants received GSK3858279 SC injection 60 milligram (mg) once per week for 12 weeks.	GSK3858279 360 mg Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.
Average Concentration Over a Dosing Interval (Cavg) of GSK3858279	2461.8 Nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 54 • Interval 54.0 to	13550.4 Nanogram per milliliter (ng/mL) Geometric Coefficient of Variation 35 • Interval 35.0 to	—

SECONDARY outcome

Timeframe: Pre-dose, Week 1, Week 4, Week 7, Week 8, Week 11, Week 12, Week 16, Week 20 and Week 27 post dose

Population: This analysis was performed on Pharmacokinetic (PK) set which included all randomized participants in the Safety Population who had at least 1 dose of GSK3858279 and at least 1 non-missing PK assessment (Non-quantifiable \[NQ\] values were considered as non-missing values). Only those participants with data available at specified time points have been analyzed.

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.

Outcome measures

Measure	Placebo n=25 Participants Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.	GSK3858279 60 mg n=25 Participants Participants received GSK3858279 SC injection 60 milligram (mg) once per week for 12 weeks.	GSK3858279 360 mg Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.
Area Under the Time-Concentration Curve (AUC) Over the Dosing Interval (AUC[0-Tau]) of GSK3858279	17232.4 Day*Nanogram per milliliter (Day*ng/mL) Geometric Coefficient of Variation 54 • Interval 54.0 to	94852.5 Day*Nanogram per milliliter (Day*ng/mL) Geometric Coefficient of Variation 35 • Interval 35.0 to	—

SECONDARY outcome

Timeframe: Baseline (Day1), Week 2, Week 4, Week 8 and Week 12

Population: The analysis was performed on the Full Analysis Set population that included all randomized participants who received at least one dose of study intervention. Number of participants with analyzable outcome (measured outcome used in estimation or imputed outcome based on composite intercurrent event strategy) at the current time point were included in the Overall Number of Participants Analyzed field.

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'.

Outcome measures

Measure	Placebo n=41 Participants Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.	GSK3858279 60 mg n=40 Participants Participants received GSK3858279 SC injection 60 milligram (mg) once per week for 12 weeks.	GSK3858279 360 mg n=43 Participants Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.
Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time Week 12	-2.07 Scores on a Scale Interval -2.65 to -1.49	-2.25 Scores on a Scale Interval -2.85 to -1.65	-1.89 Scores on a Scale Interval -2.49 to -1.29
Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time Week 2	-1.39 Scores on a Scale Interval -1.8 to -0.97	-1.04 Scores on a Scale Interval -1.46 to -0.61	-1.49 Scores on a Scale Interval -1.91 to -1.07
Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time Week 4	-1.77 Scores on a Scale Interval -2.25 to -1.29	-1.36 Scores on a Scale Interval -1.86 to -0.87	-1.44 Scores on a Scale Interval -1.95 to -0.94
Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time Week 8	-1.84 Scores on a Scale Interval -2.36 to -1.33	-1.99 Scores on a Scale Interval -2.53 to -1.46	-1.96 Scores on a Scale Interval -2.49 to -1.43

SECONDARY outcome

Timeframe: 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

Population: The analysis was performed on the Full Analysis Set population that included all randomized participants who received at least one dose of study intervention. Number of participants with analyzable outcome (measured outcome used in estimation or imputed outcome based on composite intercurrent event strategy) at the current time point were included in the Overall Number of Participants Analyzed field.

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'.

Outcome measures

Measure	Placebo n=48 Participants Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.	GSK3858279 60 mg n=48 Participants Participants received GSK3858279 SC injection 60 milligram (mg) once per week for 12 weeks.	GSK3858279 360 mg n=48 Participants Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.
Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS Week 5	-1.54 Scores on a Scale Interval -2.09 to -1.0	-1.60 Scores on a Scale Interval -2.16 to -1.04	-1.74 Scores on a Scale Interval -2.3 to -1.18
Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS Week 7	-1.63 Scores on a Scale Interval -2.18 to -1.09	-1.91 Scores on a Scale Interval -2.46 to -1.35	-1.94 Scores on a Scale Interval -2.5 to -1.38
Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS Week 8	-1.72 Scores on a Scale Interval -2.27 to -1.18	-2.10 Scores on a Scale Interval -2.66 to -1.54	-1.99 Scores on a Scale Interval -2.55 to -1.43
Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS Week 9	-1.71 Scores on a Scale Interval -2.25 to -1.18	-2.13 Scores on a Scale Interval -2.67 to -1.59	-1.94 Scores on a Scale Interval -2.49 to -1.4
Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS Week 11	-1.88 Scores on a Scale Interval -2.44 to -1.32	-2.40 Scores on a Scale Interval -2.98 to -1.83	-2.12 Scores on a Scale Interval -2.7 to -1.55
Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS Week 12	-1.85 Scores on a Scale Interval -2.44 to -1.28	-2.50 Scores on a Scale Interval -3.09 to -1.91	-2.07 Scores on a Scale Interval -2.67 to -1.48
Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS Week 1	-0.47 Scores on a Scale Interval -0.76 to -0.17	-0.57 Scores on a Scale Interval -0.87 to -0.27	-0.68 Scores on a Scale Interval -0.98 to -0.38
Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS Week 2	-0.71 Scores on a Scale Interval -1.1 to -0.32	-0.95 Scores on a Scale Interval -1.34 to -0.55	-1.16 Scores on a Scale Interval -1.55 to -0.76
Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS Week 3	-0.94 Scores on a Scale Interval -1.37 to -0.5	-1.24 Scores on a Scale Interval -1.68 to -0.8	-1.50 Scores on a Scale Interval -1.94 to -1.06
Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS Week 4	-1.34 Scores on a Scale Interval -1.81 to -0.87	-1.42 Scores on a Scale Interval -1.9 to -0.94	-1.60 Scores on a Scale Interval -2.08 to -1.11
Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS Week 6	-1.59 Scores on a Scale Interval -2.12 to -1.07	-1.71 Scores on a Scale Interval -2.24 to -1.18	-1.73 Scores on a Scale Interval -2.26 to -1.2
Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS Week 10	-1.76 Scores on a Scale Interval -2.3 to -1.22	-2.31 Scores on a Scale Interval -2.86 to -1.76	-2.01 Scores on a Scale Interval -2.56 to -1.45

SECONDARY outcome

Timeframe: At Week 12

Population: The analysis was performed on the Full Analysis Set (FAS) set that included all randomized participants who received at least one dose of study intervention. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. 'Number Analyzed' signifies participants evaluable for specified time points.

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'.

Outcome measures

Measure	Placebo n=33 Participants Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.	GSK3858279 60 mg n=32 Participants Participants received GSK3858279 SC injection 60 milligram (mg) once per week for 12 weeks.	GSK3858279 360 mg n=32 Participants Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.
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	0.50 Proportion of participants 95% Confidence Interval 0.38 • Interval 0.38 to 0.62	0.64 Proportion of participants 95% Confidence Interval 0.52 • Interval 0.52 to 0.75	0.55 Proportion of participants 95% Confidence Interval 0.43 • Interval 0.43 to 0.67

SECONDARY outcome

Timeframe: At Week 12

Population: The analysis was performed on the Full Analysis Set (FAS) set that included all randomized participants who received at least one dose of study intervention. Only those participants who were measured and analyzed (i.e., contributed data reported in the table) were included in the Overall Number of Participants Analyzed field. 'Number Analyzed' signifies participants evaluable for specified time points.

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'.

Outcome measures

Measure	Placebo n=33 Participants Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks.	GSK3858279 60 mg n=32 Participants Participants received GSK3858279 SC injection 60 milligram (mg) once per week for 12 weeks.	GSK3858279 360 mg n=32 Participants Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.
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	0.28 Proportion of participants 95% Confidence Interval 0.19 • Interval 0.19 to 0.39	0.40 Proportion of participants 95% Confidence Interval 0.29 • Interval 0.29 to 0.52	0.32 Proportion of participants 95% Confidence Interval 0.22 • Interval 0.22 to 0.44

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 11 other events

Deaths: 0 deaths

GSK3858279 60 Milligram (mg) Weekly

Serious events: 2 serious events

Other events: 9 other events

Deaths: 0 deaths

GSK3858279 360 mg Weekly

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=48 participants at risk Participants received placebo SC injection once per week for 12 weeks.	GSK3858279 60 Milligram (mg) Weekly n=48 participants at risk Participants received GSK3858279 subcutaneous (SC) injection 60 mg once per week for 12 weeks.	GSK3858279 360 mg Weekly n=48 participants at risk Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.
Cardiac disorders Angina unstable	2.1% 1/48 • Number of events 1 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
Infections and infestations Cat scratch disease	2.1% 1/48 • Number of events 1 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
Infections and infestations Pneumonia	2.1% 1/48 • Number of events 1 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	2.1% 1/48 • Number of events 1 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
Nervous system disorders Hemianopia	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	2.1% 1/48 • Number of events 1 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.1% 1/48 • Number of events 1 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	2.1% 1/48 • Number of events 1 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.

Other adverse events

Measure	Placebo n=48 participants at risk Participants received placebo SC injection once per week for 12 weeks.	GSK3858279 60 Milligram (mg) Weekly n=48 participants at risk Participants received GSK3858279 subcutaneous (SC) injection 60 mg once per week for 12 weeks.	GSK3858279 360 mg Weekly n=48 participants at risk Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks.
Infections and infestations COVID-19	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	8.3% 4/48 • Number of events 4 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	2.1% 1/48 • Number of events 1 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
Infections and infestations Upper respiratory tract infection	6.2% 3/48 • Number of events 3 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	4.2% 2/48 • Number of events 2 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
Musculoskeletal and connective tissue disorders Arthralgia	6.2% 3/48 • Number of events 4 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	6.2% 3/48 • Number of events 7 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
Nervous system disorders Dizziness	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	6.2% 3/48 • Number of events 3 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
General disorders Injection site haemorrhage	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	0.00% 0/48 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	6.2% 3/48 • Number of events 6 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
Infections and infestations Bronchitis	2.1% 1/48 • Number of events 1 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	2.1% 1/48 • Number of events 1 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	6.2% 3/48 • Number of events 3 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.
Nervous system disorders Headache	10.4% 5/48 • Number of events 7 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	4.2% 2/48 • Number of events 2 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.	4.2% 2/48 • Number of events 3 • All-cause mortality, Serious Adverse Events (SAEs) and non-Serious Adverse Events (non-SAEs) were collected from the start of the study intervention (Day 1) until follow up of week 27. Safety set included all randomized participants who took at least 1 dose of study intervention. Participants were analyzed according to the treatment they actually received.

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