Pain
Conditions
Keywords
Diabetes, Neuropathic pain, Diabetic Peripheral Neuropathic Pain (DPNP), 214221, GSK3858279, Efficacy, Safety, Pharmacokinetics, Tolerability
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.
Interventions
DRUGGSK3858279
GSK3858279 was administered
DRUGPlacebo
Placebo was administered
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Click here to enter text.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Weekly Average of Average Daily Pain Score at Week 12, Assessed on the Numeric Rating Scale (NRS) | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| 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 | 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. |
| Number of Participants With Adverse Events (AEs), Serious AE (SAEs) and AEs of Special Interest (AESI) | Up to 27 weeks | 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. |
| 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 | 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'. |
| 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 | 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'. |
| 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 | 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'. |
| 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 | 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'. |
| 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 | 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. |
Countries
Canada, China, France, Germany, Japan, Poland, South Africa, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 147 participants were enrolled in the study, Out of which 144 participants were included in the full analysis set (FAS) population.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received matching placebo subcutaneous (SC) injection once per week for 12 weeks. | 48 |
| GSK3858279 60 mg Participants received GSK3858279 SC injection 60 mg once per week for 12 weeks. | 48 |
| GSK3858279 360 mg Participants received GSK3858279 SC injection 360 mg once per week for 12 weeks. | 48 |
| Total | 144 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 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 | Pregnancy | 0 | 1 | 0 |
| Overall Study | Randomized, not treated | 2 | 0 | 1 |
| Overall Study | Study terminated by sponsor | 26 | 27 | 26 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | GSK3858279 60 mg | GSK3858279 360 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 61.3 YEARS STANDARD_DEVIATION 8.59 | 60.1 YEARS STANDARD_DEVIATION 10.18 | 60.2 YEARS STANDARD_DEVIATION 9.26 | 60.5 YEARS STANDARD_DEVIATION 9.32 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 15 Participants | 12 Participants | 14 Participants | 41 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 8 Participants | 9 Participants | 18 Participants |
| Race/Ethnicity, Customized Mixed race | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Not reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 30 Participants | 24 Participants | 25 Participants | 79 Participants |
| Sex: Female, Male Female | 21 Participants | 19 Participants | 22 Participants | 62 Participants |
| Sex: Female, Male Male | 27 Participants | 29 Participants | 26 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 48 | 0 / 48 | 0 / 48 |
| other Total, other adverse events | 11 / 48 | 9 / 48 | 10 / 48 |
| serious Total, serious adverse events | 4 / 48 | 2 / 48 | 0 / 48 |
Outcome results
Primary
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'.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| GSK3858279 60 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score at Week 12, Assessed on the Numeric Rating Scale (NRS) | -2.50 Scores on a Scale | 95% Confidence Interval -3.09 |
| GSK3858279 360 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score at Week 12, Assessed on the Numeric Rating Scale (NRS) | -2.07 Scores on a Scale | 95% Confidence Interval -2.67 |
95% CI: [-1.47, 0.18]
95% CI: [-1.04, 0.61]
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| GSK3858279 60 mg | Area Under the Time-Concentration Curve (AUC) Over the Dosing Interval (AUC[0-Tau]) of GSK3858279 | 94852.5 Day*Nanogram per milliliter (Day*ng/mL) | Geometric Coefficient of Variation 35 |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Average Concentration Over a Dosing Interval (Cavg) of GSK3858279 | 2461.8 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 54 |
| GSK3858279 60 mg | Average Concentration Over a Dosing Interval (Cavg) of GSK3858279 | 13550.4 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
Secondary
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'.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time | Week 8 | -1.84 Scores on a Scale |
| Placebo | Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time | Week 4 | -1.77 Scores on a Scale |
| Placebo | Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time | Week 2 | -1.39 Scores on a Scale |
| Placebo | Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time | Week 12 | -2.07 Scores on a Scale |
| GSK3858279 60 mg | Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time | Week 4 | -1.36 Scores on a Scale |
| GSK3858279 60 mg | Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time | Week 2 | -1.04 Scores on a Scale |
| GSK3858279 60 mg | Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time | Week 8 | -1.99 Scores on a Scale |
| GSK3858279 60 mg | Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time | Week 12 | -2.25 Scores on a Scale |
| GSK3858279 360 mg | Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time | Week 8 | -1.96 Scores on a Scale |
| GSK3858279 360 mg | Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time | Week 4 | -1.44 Scores on a Scale |
| GSK3858279 360 mg | Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time | Week 2 | -1.49 Scores on a Scale |
| GSK3858279 360 mg | Change From Baseline in the Short-Form Mcgill Pain Questionnaire Total Score Over Time | Week 12 | -1.89 Scores on a Scale |
Secondary
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'.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| GSK3858279 60 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 2 | -0.95 Scores on a Scale |
| GSK3858279 60 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 8 | -2.10 Scores on a Scale |
| GSK3858279 60 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 9 | -2.13 Scores on a Scale |
| GSK3858279 60 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 6 | -1.71 Scores on a Scale |
| GSK3858279 60 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 4 | -1.42 Scores on a Scale |
| GSK3858279 60 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 10 | -2.31 Scores on a Scale |
| GSK3858279 60 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 3 | -1.24 Scores on a Scale |
| GSK3858279 60 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 1 | -0.57 Scores on a Scale |
| GSK3858279 60 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 11 | -2.40 Scores on a Scale |
| GSK3858279 60 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 7 | -1.91 Scores on a Scale |
| GSK3858279 60 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 12 | -2.50 Scores on a Scale |
| GSK3858279 60 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 5 | -1.60 Scores on a Scale |
| GSK3858279 360 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 12 | -2.07 Scores on a Scale |
| GSK3858279 360 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 11 | -2.12 Scores on a Scale |
| GSK3858279 360 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 1 | -0.68 Scores on a Scale |
| GSK3858279 360 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 2 | -1.16 Scores on a Scale |
| GSK3858279 360 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 3 | -1.50 Scores on a Scale |
| GSK3858279 360 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 4 | -1.60 Scores on a Scale |
| GSK3858279 360 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 5 | -1.74 Scores on a Scale |
| GSK3858279 360 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 6 | -1.73 Scores on a Scale |
| GSK3858279 360 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 7 | -1.94 Scores on a Scale |
| GSK3858279 360 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 8 | -1.99 Scores on a Scale |
| GSK3858279 360 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 9 | -1.94 Scores on a Scale |
| GSK3858279 360 mg | Change From Baseline in the Weekly Average of Average Daily Pain Score Over Time, Assessed on the NRS | Week 10 | -2.01 Scores on a Scale |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Concentration (Cmax) of GSK3858279 | 2943.3 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 58 |
| GSK3858279 60 mg | Maximum Concentration (Cmax) of GSK3858279 | 17125.9 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 34 |
Secondary
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Adverse Events (AEs), Serious AE (SAEs) and AEs of Special Interest (AESI) | Any AESI | 6 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious AE (SAEs) and AEs of Special Interest (AESI) | Any SAE | 4 Participants |
| Placebo | Number of Participants With Adverse Events (AEs), Serious AE (SAEs) and AEs of Special Interest (AESI) | Any AE | 27 Participants |
| GSK3858279 60 mg | Number of Participants With Adverse Events (AEs), Serious AE (SAEs) and AEs of Special Interest (AESI) | Any AESI | 4 Participants |
| GSK3858279 60 mg | Number of Participants With Adverse Events (AEs), Serious AE (SAEs) and AEs of Special Interest (AESI) | Any AE | 23 Participants |
| GSK3858279 60 mg | Number of Participants With Adverse Events (AEs), Serious AE (SAEs) and AEs of Special Interest (AESI) | Any SAE | 2 Participants |
| GSK3858279 360 mg | Number of Participants With Adverse Events (AEs), Serious AE (SAEs) and AEs of Special Interest (AESI) | Any AESI | 5 Participants |
| GSK3858279 360 mg | Number of Participants With Adverse Events (AEs), Serious AE (SAEs) and AEs of Special Interest (AESI) | Any SAE | 0 Participants |
| GSK3858279 360 mg | Number of Participants With Adverse Events (AEs), Serious AE (SAEs) and AEs of Special Interest (AESI) | Any AE | 24 Participants |
Secondary
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| GSK3858279 60 mg | 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 |
| GSK3858279 60 mg | 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 | 1 Participants |
| GSK3858279 360 mg | 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 |
| GSK3858279 360 mg | 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 |
Secondary
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'.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| GSK3858279 60 mg | 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 | 0.64 Proportion of participants | 95% Confidence Interval 0.52 |
| GSK3858279 360 mg | 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 | 0.55 Proportion of participants | 95% Confidence Interval 0.43 |
Secondary
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'.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| GSK3858279 60 mg | 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 | 0.40 Proportion of participants | 95% Confidence Interval 0.29 |
| GSK3858279 360 mg | 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 | 0.32 Proportion of participants | 95% Confidence Interval 0.22 |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to Maximum Concentration (Tmax) of GSK3858279 | 1.518 Day | Full Range 0.64 |
| GSK3858279 60 mg | Time to Maximum Concentration (Tmax) of GSK3858279 | 1.360 Day | Full Range 0.47 |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Trough Concentration at the End of the Dosing Interval (Ctau) of GSK3858279 | 1910.4 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 52 |
| GSK3858279 60 mg | Trough Concentration at the End of the Dosing Interval (Ctau) of GSK3858279 | 9543.2 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 43 |