Dermatitis, Atopic
Conditions
Keywords
Dermatitis, Atopic, GSK1070806, 219538, Eczema, Skin Diseases, Safety, Efficacy, Immune System Diseases
Brief summary
This study is parallel group, placebo-controlled dose-ranging study to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of GSK1070806 in adult participants with moderate to severe Atopic Dermatitis (AtD), who have previously been treated with medicated topical treatments or a biologic therapy.
Interventions
DRUGGSK1070806
GSK1070806 will be administered.
DRUGPlacebo
Placebo will be administered.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Participants and investigator are blinded to study intervention.
Intervention model description
This is a dose finding, placebo-controlled study where participants will be randomized to receive either GSK1070806 or placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Adult participants 18 years to 75 years of age * Participants with: * AtD defined by the AAD Consensus Criteria. * Diagnosis of AtD ≥1 year. * An IGA score ≥3. * AtD involvement of ≥10% body surface area (BSA). * EASI score ≥16 * Baseline pruritus numerical rating scale average score for maximum intensity of at least 3. * Participants may have had exposure to 1 biologic therapy meeting at least 1 of the following conditions: * Participants who stopped treatment due to non-response, partial response, loss of efficacy. * Participants who stopped treatment due to intolerance or AEs. * Participant with a recent history less than or equal to (≤6) months prior to the Screening visit) of inadequate response to a stable regimen of prescription topical medication. * Participants for whom prescription topical medications are not tolerated. * Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical study
Exclusion criteria
* Chronic or acute infection requiring treatment with oral or IV antibiotics, antivirals, anti-protozoal, or antifungals within 4 weeks before the Screening visit or anytime between the Screening and Baseline visits. * Superficial skin infections within 1 week before the Screening visit or active infections (including localized infections), or history of recurrent infections (excluding recurrent fungal infections of the nail bed) * Known, pre-existing or suspected parasitic infection within 6 months before the Screening visit. * Symptomatic herpes zoster within 3 months prior to screening * Uncontrolled hypertension. * Current or chronic history of liver disease or known hepatic or biliary abnormalities. * Known or suspected history of immunosuppression, including history of invasive opportunistic infections despite infection resolution or unusually frequent, recurrent, or prolonged infections, per the Investigator's judgment. * Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years * Breast cancer within the past 10 years. * History or presence of significant medical illness including but not limited to cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, neurological, or psychiatric disorders which in the opinion of the investigator would interfere with the study procedures and/or assessments. * Previously treated with any oral Janus Kinase inhibitor (JAKi) or other kinase inhibitors, experimental or approved. * Uncontrolled chronic disease that might require bursts of oral corticosteroids, e.g., co-morbid severe uncontrolled asthma. * Presence of Hepatitis B surface antibody (HBsAg) or Hepatitis B core antibody (HBcAb) at screening or within 3 months prior to first dose of study intervention. * Positive hepatitis C antibody test result at screening or within 3 months prior to starting study intervention. * Positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention. * Positive HIV antibody test. * Evidence of active or latent TB as documented by medical history, examination, and TB testing with a positive QuantiFERON test at initial Screening visit. * Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline (CFB) in Eczema Area and Severity Index (EASI) Score at Week 16 | Baseline (Day 1) and Week 16 | EASI scoring system is standardized clinical tool for assessment of extent (area) \& severity of atopic dermatitis(AtD). Severity of clinical signs of AtD (erythema, induration/papulation, excoriation \& lichenification) scored separately for each of 4 body regions (head \& neck, upper limbs, trunk \& lower limbs) on 4-point scale: 0=absent;1=mild;2=moderate;3=severe. EASI area score was based upon % body surface area with AtD in body region:0=0%, 1=1-9%;2=10-29%;3=30-49%;4=50-69%;5=70-89%;6=90-100%. Final EASI score was obtained by multiplying EASI area scores (0-6) with severity scores (0-3) of all 4 body regions; it ranges from 0 to 72, with higher scores= more severe or extensive condition. Baseline=last value/assessment before first dose of study treatment (ST) (Day1) based on date \& time of assessment (ToA) \& treatment. CFB =post-dose visit (Week 16) value minus Baseline value. Percent CFB was calculated by dividing CFB value by Baseline value and multiplying it by 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline (CFB) in EASI Score at Each Time Point | Baseline (Day 1), Weeks 1, 2, 4, 6, 8, 10, 12, 14, and 16 | EASI scoring system is standardized clinical tool for assessment of extent (area) \& severity of atopic dermatitis(AtD). Severity of clinical signs of AtD (erythema, induration/papulation, excoriation \& lichenification) scored separately for each of 4 body regions (head \& neck, upper limbs, trunk \& lower limbs) on 4-point scale: 0=absent;1=mild;2=moderate;3=severe. EASI area score was based upon % body surface area with AtD in body region:0=0%, 1=1-9%;2=10-29%;3=30-49%;4=50-69%;5=70-89%;6=90-100%. Final EASI score was obtained by multiplying EASI area scores (0-6) with severity scores (0-3) of all 4 body regions; it ranges from 0 to 72, with higher scores= more severe or extensive condition. Baseline=last value/assessment before first dose of ST (Day1) based on date \& ToA \& treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Percent CFB was calculated by dividing CFB value by Baseline value and multiplying it by 100. |
| Number of Participants Who Achieved Reduction of Greater Than or Equal to (>=) 75 Percent (%) in EASI Score From Baseline at Week 16 | Baseline (Day 1) and Week 16 | EASI scoring system is standardized clinical tool for assessment of extent (area) \& severity of atopic dermatitis(AtD). Severity of clinical signs of AtD (erythema, induration/papulation, excoriation \& lichenification) scored separately for each of 4 body regions (head \& neck, upper limbs, trunk \& lower limbs) on 4-point scale: 0=absent;1=mild;2=moderate;3=severe. EASI area score was based upon % body surface area with AtD in body region:0=0%, 1=1-9%;2=10-29%;3=30-49%;4=50-69%;5=70-89%;6=90-100%. Final EASI score was obtained by multiplying EASI area scores (0-6) with severity scores (0-3) of all 4 body regions; it ranges from 0 to 72, with higher scores= more severe or extensive condition. Baseline was the last value/assessment before first dose of study treatment (Day1) based on date \& time of assessment \& treatment. |
| Number of Participants Who Achieved Investigator's Global Assessment (IGA) Score of 0 or 1 and Had a Reduction of >=2 Points From Baseline at Week 16 | Baseline (Day 1) and Week 16 | The Investigator Global Assessment (IGA) is a clinical tool for assessing the current state/severity of a participant's atopic dermatitis. It is a static 5-point morphological assessment of overall disease severity determined by the investigator, sub-investigator, or trained healthcare professional with required qualifications on a scale of 0 to 4 where, 0=clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe. Higher score indicates high severity of disease. IGA 0/1 responders are participants whose IGA score is 'Clear' (0) or 'Almost Clear' (1) and had a reduction of \>=2 points from Baseline at Week 16. Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. |
| Change From Baseline in Peak Pruritus Numerical Rating Scale (PP-NRS) Score at Week 16 | Baseline (Day -7 to Day -1) and Week 16 | PP-NRS is a patient reported measure of pruritus (itch) intensity assessing worst itch (in the past 24 hours). The values were evaluated using an 11-point scale (from 0 to 10), with 0 being no itch and 10 being the worst imaginable itch. Baseline was averaged from daily values from Day -7 to Day -1 prior to first dose of study treatment (Day 1); post-dose visit i.e. Week 16 used average of 7 daily values from Days 106 to 112 prior to Week 16 (Day 113). Change from Baseline (CFB) was calculated by subtracting Baseline value from the post-dose (PD) visit (Week 16) value. |
| Number of Participants Who Achieved Reduction of >=4 Points in PP-NRS Score From Baseline at Week 16 | Baseline (Day -7 to Day -1) and Week 16 | PP-NRS is a patient reported measure of pruritus (itch) intensity assessing worst itch (in the past 24 hours). The values were evaluated using an 11-point scale (from 0 to 10), with 0 being no itch and 10 being the worst imaginable itch. Baseline was averaged from daily values from Day -7 to Day -1 prior to first dose of study treatment (Day 1); post-dose visit i.e. Week 16 used average of 7 daily values from Days 106 to 112 prior to Week 16 (Day 113). |
| Number of Participants Who Achieved Reduction of >=50%, >=90% or 100% in EASI Score From Baseline at Week 16 | Baseline (Day 1) and Week 16 | EASI scoring system is standardized clinical tool for assessment of extent (area) \& severity of atopic dermatitis(AtD). Severity of clinical signs of AtD (erythema, induration/papulation, excoriation \& lichenification) scored separately for each of 4 body regions (head \& neck, upper limbs, trunk \& lower limbs) on 4-point scale: 0=absent;1=mild;2=moderate;3=severe. EASI area score was based upon % body surface area with AtD in body region:0=0%, 1=1-9%;2=10-29%;3=30-49%;4=50-69%;5=70-89%;6=90-100%. Final EASI score was obtained by multiplying EASI area scores (0-6) with severity scores (0-3) of all 4 body regions; it ranges from 0 to 72, with higher scores= more severe or extensive condition. Baseline was the last value/assessment before first dose of study treatment (Day 1) based on date \& time of assessment \& treatment. |
| Number of Participants Who Achieved Reduction of >=50% or >=75% in Scoring Atopic Dermatitis (SCORAD) Score From Baseline at Week 16 | Baseline (Day 1) and Week 16 | SCORAD was used to standardize the extent and severity of AtD. It consisted of 3 components i.e., A=extent or affected BSA assessed as a % of each defined body area and reported as sum of all areas, with a maximum score of 100%.B=severity of 6 specific symptoms of AtD (redness, swelling, oozing/crusting, excoriation, skin thickening/lichenification, dryness) assessed using following scale: none=0,mild=1,moderate=2, or severe=3 (for a maximum of 18 total points) \& C=pruritus (itch) \& sleep loss scored by participants on VAS, where "0"=no itch(or no sleeplessness) \& "10"=worst imaginable itch(or sleeplessness) with a maximum score of 20. SCORAD total score was calculated using these 3 aspects: extent (A: 0-100), severity (B: 0-18), \& subjective symptoms (C: 0-20) using the formula: A/5 + 7\*B/2+ C. SCORAD total score ranged from 0 to 103, where 0=no disease to 103=severe disease. Higher values of SCORAD=worse outcome. |
| Change From Baseline in the Body Surface Area (BSA) at Week 16 | Baseline (Day 1) and Week 16 | The BSA assessment estimates the extent of disease or skin involvement with respect to AtD and is expressed as a percentage of total body surface area. BSA were determined by the Investigator or designee using the participant's palm = 1% rule i.e. the surface area of the participant's palm (including fingers) is approximately 1% of the total BSA. Investigators applied this rule to quickly estimate the percentage of skin affected by AtD without complex calculations (for example- if the affected area equals 10 palms, this corresponded to approximately 10% BSA involvement). Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| Change From Baseline in the SCORAD Score at Week 16 | Baseline (Day 1) and Week 16 | SCORAD was used to standardize the extent and severity of AtD. It consisted of 3 components i.e., A=extent or affected BSA assessed as a % of each defined body area and reported as sum of all areas, with a maximum score of 100%.B=severity of 6 specific symptoms of AtD (redness, swelling, oozing/crusting, excoriation, skin thickening/lichenification, dryness) assessed using following scale: none=0,mild=1,moderate=2, or severe=3 (for a maximum of 18 total points) \& C=pruritus (itch) \& sleep loss scored by participants on VAS, where "0"=no itch(or no sleeplessness) \& "10"=worst imaginable itch(or sleeplessness) with a maximum score of 20. SCORAD total score was calculated using these 3 aspects: extent (A: 0-100), severity (B: 0-18), \& subjective symptoms (C: 0-20) using the formula: A/5 + 7\*B/2+ C. SCORAD total score ranged from 0 to 103, where 0=no disease to 103=severe disease. Higher values of SCORAD=worse outcome. |
| Change From Baseline in Patient Reported Outcomes (PRO) Measure of Skin Pain Numerical Rating Scale (SP-NRS) Score at Week 16 | Baseline (Day -7 to Day -1) and Week 16 | SP-NRS is a patient reported measure assessing worst level of skin pain (in the past 24 hours). The values were evaluated using an 11-point scale from 0 to 10, with 0 being no pain and 10 being the worst pain imaginable. Baseline was averaged from daily values from Day -7 to Day -1 prior to first dose of study treatment (Day 1); post-dose visit i.e. Week 16 used average of 7 daily values from Days 106 to 112 prior to Week 16 (Day 113). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| Change From Baseline in PRO Measure of Patient Reported Outcomes Measurement Information System (PROMIS) -Sleep Disturbance 8b at Week 16 | Baseline (Day 1) and Week 16 | The PROMIS sleep disturbance 8b is a PRO instrument designed to assess participant's self-reported sleep disturbance for which the recall period is the past 7 days. It measures perceptions of sleep quality, depth, and restoration associated with sleep. It contains 8 questions (hence "8b"), these questions are rated using 5-point verbal rating scale (i.e., 1 = very much to 5 = not at all). These are summed to get a total score which ranges from 8 to 40, with higher scores indicating greater severity of sleep disturbance. Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| Change From Baseline in PRO Measure of Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Score at Week 16 | Baseline (Day 1) and Week 16 | The FACIT-Fatigue scale is a short, 13-item measure that assesses participant's self-reported fatigue and its associated impact for daily activities over the past week. The items are rated on a 5-point Likert-type scale: (i.e., 0 = very much to 4 = not at all), where a higher score indicates a better outcome (no fatigue). The total score was derived by summing rating of all 13 items, which ranges from 0 to 52, with 0 being the worst possible score and 52 indicating no fatigue. Higher score indicates an improvement in the participant's health status and decrease in the score indicates worse fatigue/quality of life (QoL). Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| Change From Baseline in PRO Measure of Brief Fatigue Inventory (BFI) - Item 3 at Week 16 | Baseline (Day -7 to Day -1) and Week 16 | The BFI is a self-administered questionnaire developed to assess fatigue severity. The BFI has 9 items. BFI- Item 3 assesses the worst level of fatigue during the past 24 hours. Participants report their worst level of fatigue daily, for the previous 24 hours, using a numerical rating scale ranging from 0 (no fatigue) to 10 (as bad as you can imagine). The BFI item 3 score ranges from 0 to 10, higher score indicates worst outcome. Baseline was averaged from daily values from Day -7 to Day -1 prior to first dose of study treatment (Day 1); post-dose visit i.e. Week 16 used average of 7 daily values from Days 106 to 112 prior to Week 16 (Day 113). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| Change From Baseline in PRO Measure of Patient Oriented Eczema Measure (POEM) at Week 16 | Baseline (Day 1) and Week 16 | POEM is a 7-item questionnaire that assesses symptoms of dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping over the last week. Each item is scored from 0 to 4, where 0 = 'no days', 1 = '1 to 2 days', 2 = '3 to 4 days', 3 = '5 to 6' days, and 4 = 'every day'). The total score was derived by summing scores of all 7-items. Total score ranges from 0 (absent disease) to 28 (severe disease). Higher score indicates poor QoL. Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose (Week 16) visit value. |
| Change From Baseline in PRO Measure of Dermatology Life Quality Index (DLQI) Score at Week 16 | Baseline (Day 1) and Week 16 | The DLQI is a 10-item questionnaire that asks participants to evaluate the degree that their skin disease has affected their QoL. Each question was evaluated on a 4-point scale (range 0 to 3) where, 0 = not at all, 1= a little, 2= a lot, 3= very much, higher scores indicated more impact on quality of life. Scores from all 10 questions were added up to give DLQI total score. The total DLQI score ranges from 0 (not at all) to 30 (very much). Higher scores indicated more impaired quality of life. Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| Change From Baseline in PRO Measure of Hospital Anxiety and Depression Scale (HADS) - Anxiety Subscale Score at Week 16 | Baseline (Day 1) and Week 16 | HADS was a validated 14-item self-reported questionnaire to assess states of anxiety and depression over the past week. HADS consisted of 2 subscales: HADS-Anxiety (HADS-A) scale and HADS-Depression (HADS-D) scale. HADS-A assessed state of generalized anxiety. It comprised of 7 items. Each item was rated on a 4-point scale, with scores ranging from 0 (no, not at all) to 3 (yes, definitely), where higher scores indicated more anxiety/depression symptoms. HADS-A total score was calculated as the sum of all 7 items with score ranging from 0 (no presence of anxiety) to 21 (severe feeling of anxiety); higher score indicated greater severity of anxiety. Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. Data of HADS-anxiety subscale score has been presented. |
| Change From Baseline in PRO Measure of HADS-Depression Subscale Score at Week 16 | Baseline (Day 1) and Week 16 | HADS was a validated 14-item self-reported questionnaire to assess states of anxiety and depression over the past week. HADS consisted of 2 subscales: HADS-Anxiety (HADS-A) scale and HADS-Depression (HADS-D) scale. HADS-D assessed state of depression. It comprised of 7 items. Each item was rated on a 4-point scale, with scores ranging from 0 (no, not at all) to 3 (yes, definitely), where higher scores indicated more anxiety/depression symptoms. HADS-D total score was calculated as the sum of all 7 items with score ranging from 0 (no presence of depression) to 21 (severe feeling of depression); higher score indicated greater severity of depression. Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. Data of HADS-depression subscale score has been presented. |
| Change From Baseline in PRO Measure of Work Productivity and Activity Impairment Questionnaire-Atopic Dermatitis (WPAI- AD) at Week 16 | Baseline (Day 1) and Week 16 | The WPAI-AD is a concise,6-item questionnaire that evaluates the impact of atopic dermatitis on both work and daily activities, yielding 4 percentage-based impairment scores, each range from 0 to 100%. Higher values=greater impairment. Calculation of these 4 scores are as follows: 1. Work time missed due to health (Absenteeism) (%)=hours missed due to health divided by (hours missed due to health+hours missed for other reasons+hours actually worked) \*100. 2. Impairment while working due to health (Presenteeism) (%)=Question (Q)5 score (from 0 to 10) divided by 10\*100. 3. Overall work impairment due to health (%)=Absenteeism+(1-Absenteeism fraction)\*Presenteeism. 4. Activity impairment due to health (%)=Q6 score (from 0 to 10) divided by 10\*100.Baseline was the last value/assessment before the first dose of study treatment (Day1) based on date and time of the assessment and treatment. CFB was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| Number of Participants With Adverse Events (AEs), Serious AE (SAEs), and AEs of Special Interest (AESI) | Up to Week 28 | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with use of a study intervention, whether or not considered related to study intervention. Any untoward medical occurrence that, at any dose, results in death, Is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, Is a congenital anomaly/birth defect in the offspring of a study participant, abnormal pregnancy outcomes, Is a suspected transmission of any infectious agent via an authorized medicinal product and medically important were categorized as SAE. AESIs of the study drug includes serious and opportunistic infections, serious hypersensitivity reactions and injection site reactions. |
| Change From Baseline in Hematology Parameter: Hemoglobin (Hb) | Baseline (Day 1) and Week 16 | Blood samples were collected to analyze hematology parameter: hemoglobin. Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets | Baseline (Day 1) and Week 16 | Blood samples were collected to analyze Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets. Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| Change From Baseline in Hematology Parameter: Erythrocytes | Baseline (Day 1) and Week 16 | Blood samples were collected to analyze hematology parameter: erythrocytes. Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| Change From Baseline in Hematology Parameter: Hematocrit | Baseline (Day 1) and Week 16 | Blood samples were collected to analyze hematology parameter: hematocrit. Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| Change From Baseline in Hematology Parameter: Prothrombin International Normalized Ratio | Baseline (Day 1) and Week 16 | Blood samples were collected to analyze hematology parameter: Prothrombin International Normalized Ratio. Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Gamma-Glutamyl Transferase (GGT) | Baseline (Day 1) and Week 16 | Blood samples were collected to analyze clinical chemical parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Gamma-Glutamyl Transferase (GGT). Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| Change From Baseline in Clinical Chemistry Parameter: Total Bilirubin, Direct Bilirubin, and Creatinine | Baseline (Day 1) and Week 16 | Blood samples were collected to analyze clinical chemical parameters: Total Bilirubin, Direct Bilirubin, and Creatinine. Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| Change From Baseline in Chemistry Parameters: Glucose and Urea | Baseline (Day 1) and Week 16 | Blood samples were collected to analyze chemistry parameters: glucose and urea. Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| Change From Baseline in Chemistry Parameter: Albumin | Baseline (Day 1) and Week 16 | Blood samples were collected to analyze chemistry parameter: albumin. Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| Change From Baseline in Chemistry Parameter: Estimated Glomerular Filtration Rate | Baseline (Day 1) and Week 16 | Blood samples were collected to analyze chemistry parameter: Estimated Glomerular Filtration Rate. Baseline was the last value/assessment before the first dose of study treatment (Day 1) based on date and time of the assessment and treatment. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit (Week 16) value. |
| 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 Week 28 | The laboratory measurements included hematology and clinical chemistry. The parameters evaluated were albumin, glomerular filtration rate from creatinine adjusted for body surface area, glucose, potassium, sodium, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatinine, gamma glutamyl transferase, activated partial thromboplastin time, hemoglobin, leukocytes, lymphocytes, neutrophils, platelets, prothrombin international normalized ratio, eosinophils, and fibrinogen. Worst case grade increase from Baseline grade was evaluated for all the laboratory tests that were gradable by NCI CTCAE. Data is presented for only those parameters for which participants had worst case \>= Grade 3 abnormalities. |
Countries
Argentina, Bulgaria, Canada, China, Czechia, France, Germany, Greece, Italy, Japan, Mexico, Panama, Poland, South Korea, Spain, Thailand, United States
Contacts
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Participant flow
Recruitment details
A total of 161 participants were enrolled and randomized, however only 159 participants were included in Full Analysis Set (FAS) as 2 participants were never dosed following randomization. FAS included all randomized participants who received at least 1 dose of study treatment. This population was based on the treatment the participant was randomized to. This study was terminated after meeting the pre-defined futility criteria for efficacy.
Pre-assignment details
Dosing information (dose levels and frequency) has not been disclosed as it is considered as commercially confidential information (CCI). Dose levels are presented as Dose levels 1 to 4 along with directionality of the dosage within each arm/group.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 34.1 YEARS STANDARD_DEVIATION 12.72 |
| Race/Ethnicity, Customized AMERICAN INDIAN OR ALASKA NATIVE | 6 Participants |
| Race/Ethnicity, Customized ASIAN | 54 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 0 Participants |
| Race/Ethnicity, Customized MIXED RACE | 5 Participants |
| Race/Ethnicity, Customized NOT REPORTED | 8 Participants |
| Race/Ethnicity, Customized UNKNOWN | 0 Participants |
| Race/Ethnicity, Customized WHITE | 71 Participants |
| Sex: Female, Male Female | 67 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 46 | 0 / 21 | 0 / 25 | 0 / 21 | 0 / 46 |
| other Total, other adverse events | 10 / 46 | 5 / 21 | 9 / 25 | 9 / 21 | 12 / 46 |
| serious Total, serious adverse events | 0 / 46 | 0 / 21 | 0 / 25 | 1 / 21 | 1 / 46 |
Outcome results
None listed