A Dose-Finding Study of GSK2894512 Cream in Subjects With Plaque Psoriasis

Psoriasis Clinical Trial

Official title:

Study 203120: A Randomized, Blinded, Vehicle-Controlled, Dose-Finding Study of GSK2894512 Cream for the Treatment of Plaque Psoriasis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02564042
• Other study ID #: 203120
• Status: Completed
• Phase: Phase 2
• First received: September 28, 2015
• Last updated: November 1, 2017
• Start date: November 23, 2015
• Est. completion date: October 5, 2016

Study information

• Verified date: October 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy and safety of two concentrations (0.5 percent [%] and 1%) and two application frequencies (once a day and twice a day) of GSK2894512 cream for the topical treatment in subjects with plaque psoriasis. Results from this study will be considered when selecting the most appropriate concentration of GSK2894512 cream and dosing frequency in future clinical safety and efficacy studies. This is a multicenter (United States, Canada, and Japan), randomized, double-blind (sponsor-unblind), vehicle-controlled, 6-arm, parallel-group, dose-finding study. Two concentrations of GSK2894512 cream (0.5% and 1%) and a vehicle control cream will be equally randomized and evaluated following application to all psoriasis lesions (except on the scalp) once daily (evening) or twice daily (morning and evening) for 12 weeks. This study will consist of 3 periods: up to 4 weeks screening, 12 weeks double-blind treatment, and 4 weeks post-treatment follow-up. The total duration of subject participation will be approximately 16 to 20 weeks. Approximately 270 adult males and females subjects with plaque psoriasis will be screened in order to have at least 228 randomized subjects (38 subjects for each of the 6 treatment groups) and approximately 204 evaluable subjects overall. Approximately 30 subjects will be randomized in Japan to achieve at least 24 evaluable Japanese subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 227
• Est. completion date: October 5, 2016
• Est. primary completion date: October 1, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Male or female between 18 to 65 years of age inclusive, at the time of signing the informed consent.

• Confirmed clinical diagnosis of chronic stable plaque psoriasis for >=6 months.

• Body surface area involvement >=1% and <=15%, excluding scalp, at Screening and Baseline.

• A PGA of psoriasis score >=2 at Baseline.

• One target plaque located on the trunk or proximal parts of extremities (excluding knees, elbows, and intertriginous areas) that is at least 3 (centimetre) cm ? 3 cm in size at Screening and Baseline with a severity representative of the subject's overall disease.

• A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: 1) Pre-menopausal females with one of the following procedures documented: tubal ligation; hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; bilateral oophorectomy. 2) Post-menopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone and estradiol levels consistent with menopause and falling into the central laboratory's postmenopausal reference range is confirmatory). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt are required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment; Reproductive potential and agrees to follow one of the options listed in the modified list of highly effective methods for avoiding pregnancy in females of reproductive potential from 30 days prior to the first dose of study medication and until (at least five terminal half-lives OR until any continuing pharmacologic effect has ended, whichever is longer) after the last dose of study medication and completion of the follow-up visit.

Exclusion Criteria:

• Any sign of infection of any of the psoriatic lesions.

• A history or ongoing serious illness or medical, physical, or psychiatric condition(s) that, in the investigator's opinion, may interfere with the subject's completion of the study.

• Known hypersensitivity to the study treatment excipients, or a history of drug or other allergy that, in the opinion of the investigator, contraindicates participation.

• Current or chronic history of liver disease, known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), presence of hepatitis B surface antigen, or positive hepatitis C antibody test result within 3 months of screening.

• Liver function tests: alanine aminotransferase >=2x upper limit of normal (ULN); alkaline phosphatase and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

• QTc >=450 milliseconds (msec) or QTc >=480 msec for subjects with bundle branch block.

NOTES: The QTc is the QT interval corrected for heart rate according to Fridericia's formula (QTcF), with machine over-read. The QTc should be based on a single ECG obtained over a brief recording period. If QTc is outside of the threshold value, triplicate ECGs may be performed with the QTc values averaged.

• Ultraviolet (UV) light therapy or prolonged exposure to natural or artificial sources of UV radiation (eg, sunlight or tanning booth) within 4 weeks prior to the baseline visit and/or intention to have such exposure during the study, which is thought by the investigator to potentially impact the subject's psoriasis.

• Used any of the following treatments within the indicated washout period before the baseline visit: 1) 12 weeks or 5 half-lives (whichever is longer) - biologic agents (eg, 24 weeks for alefacept, 12 weeks for etanercept, 15 weeks for ustekinumab); 2) 12 weeks - oral retinoids (eg, acitretin or isotretinoin); 3) 8 weeks - cyclosporin, interferon, methotrexate, other systemic immunosuppressive or immunomodulating agents, or psoralen plus UVA light treatment; 4) 4 weeks - systemic corticosteroids or adrenocorticotropic hormone analogs; 5) 2 weeks - immunizations; drugs known to possibly worsen psoriasis, such as beta-blockers (eg, propranolol), lithium, iodides, angiotensin-converting enzyme inhibitors, and indomethacin, unless on a stable dose for >12 weeks; 6) 2 weeks - topical treatments: corticosteroids, immunomodulators, anthralin (dithranol), Vitamin D derivatives, retinoids, or coal tar (used on the body).

• Participated in a clinical study and received an investigational product within the following time period prior to the baseline visit: 4 weeks, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer).

• History of alcohol or other substance abuse within the last 2 years.

• Participated in a previous study using GSK2894512 (or WBI-1001).

Related Conditions & MeSH terms

• Psoriasis

Intervention

Drug:
• GSK2894512 1% Cream
1.0% (10 mg/g) GSK2894512 will be supplied as white to off-white cream to be applied topically
• GSK2894512 0.5% Cream
0.5% (5 mg/g) GSK2894512 will be supplied as white to off-white cream to be applied topically
• Vehicle cream
White to off-white vehicle cream base to be applied topically

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Hamilton	Ontario
Canada	GSK Investigational Site	Markham	Ontario
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	North Bay	Ontario
Canada	GSK Investigational Site	Oakville	Ontario
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Peterborough	Ontario
Canada	GSK Investigational Site	Quebec City	Quebec
Canada	GSK Investigational Site	Richmond Hill	Ontario
Canada	GSK Investigational Site	Surrey	British Columbia
Canada	GSK Investigational Site	Waterloo	Ontario
Canada	GSK Investigational Site	Windsor	Ontario
Canada	GSK Investigational Site	Windsor	Ontario
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kumamoto
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Fort Gratiot Township	Michigan
United States	GSK Investigational Site	Goodlettsville	Tennessee
United States	GSK Investigational Site	High Point	North Carolina
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Johnston	Rhode Island
United States	GSK Investigational Site	Louisville	Kentucky
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	North Logan	Connecticut
United States	GSK Investigational Site	Overland Park	Kansas
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Plainfield	Indiana
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Webster	Texas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Canada,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Have a Physician Global Assessment (PGA) Score of 0 or 1 at Week 12 and a Minimum 2-grade Improvement in PGA Score From Baseline to Week 12	The PGA is a clinical tool for assessing the current state/severity of a participant's psoriasis. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, plaque thickness, and scaling as guidelines. Each assessment was made as a visual 'average' of the severity of all treated areas at the time of the assessment. The scores ranged from 0 to 4 where 0 = Clear, 1 = Almost Clear, 2 = Mild, 3 = Moderate and 4=Severe. The percentage of responders that is, participants who achieved a PGA score of 0 or 1 and a minimum 2-grade improvement from Baseline were summarized. Baseline was defined as the latest assessment prior to the first dose. The analysis was performed on modified intent-to-treat (mITT) Population which comprised of all randomized participants except those enrolled at center ID 220008.	Baseline and up to Week 12
Secondary	Percentage of Participants With >=75 Percent Improvement in Psoriasis Area and Severity Index (PASI) From Baseline to Each Study Visit	The PASI is a standard clinical tool for assessing the severity of psoriasis based on severity of erythema, thickness and scale, as well as the extent of body surface area (BSA) affected with psoriasis. The 3 clinical signs were graded on a 5 point scale (0 to 4) and the % BSA affected was scored on a 7-point scale (0 to 6) for each of the 4 specified body regions (head, upper extremities, trunk and lower extremities). The individual scores were multiplied by a weighted factor for each body region. The sum of these scores gave the overall PASI score. Higher scores indicated more severe disease. The percentage of participants with >=75% improvement in PASI from Baseline were summarized. Baseline was defined as the latest assessment prior to the first dose. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 16
Secondary	Percentage of Participants With a Minimum 2 Grade Improvement in PGA Score From Baseline to Each Study Visit	The PGA is a clinical tool for assessing the current state/severity of a participant's psoriasis. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, plaque thickness, and scaling as guidelines. Each assessment was made as a visual 'average' of the severity of all treated areas at the time of the assessment. The scores ranged from 0 to 4 where 0 = Clear, 1 = Almost Clear, 2 = Mild, 3 = Moderate and 4=Severe. The percentage of participants who achieved a minimum 2-grade improvement from Baseline for each study visit were summarized. Baseline was defined as the latest assessment prior to the first dose. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 16
Secondary	Percentage of Participants With a PGA Score of 0 or 1 at Each Study Visit	The PGA is a clinical tool for assessing the current state/severity of a participant's psoriasis. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, plaque thickness, and scaling as guidelines. Each assessment was made as a visual 'average' of the severity of all treated areas at the time of the assessment. The scores ranged from 0 to 4 where 0 = Clear, 1 = Almost Clear, 2 = Mild, 3 = Moderate and 4=Severe. The percentage of participants who achieved a PGA score of 0 or 1 from Baseline at each study visit was summarized. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Up to Week 16
Secondary	Mean Change in Percent of BSA Affected With Psoriasis From Baseline to Each Study Visit	The extent of BSA affected by psoriasis is a general indicator of disease severity and was measured throughout the study. The extent of BSA to which study treatment was applied was also recorded. For the purpose of approximate clinical estimation, the total palmar surface of the palm plus 5 digits was assumed to be approximately equivalent to 1 percent BSA. Assessment of BSA affected with psoriasis was performed separately for four body surface regions: the head, the upper extremities, the trunk and the lower extremities, corresponding to 10, 20, 30 and 40 percent of the total body area, respectively. The mean change in percent BSA affected from Baseline was summarized for each study visit. Baseline was defined as the latest assessment prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 16
Secondary	Mean Change in PASI Score From Baseline to Each Study Visit	The PASI is a standard clinical tool for assessing the severity of psoriasis based on severity of erythema, thickness and scale, as well as the extent of BSA affected with psoriasis. The 3 clinical signs were graded on a 5 point scale (0=None to 4=Severe) and the percent of BSA affected is scored on a 7-point scale (0=0% involvement to 6=90-100%) for each of 4 specified body regions (head, upper extremities, trunk and lower extremities). The individual scores were multiplied by a weighted factor for each body region. The sum of these scores gave the overall PASI score. PASI score ranged from 0=no psoriasis to 72=worse psoriasis. The mean change in PASI score from Baseline was summarized for each study visit. Baseline was the latest assessment prior to the first dose and change from Baseline was defined as the value at post dose visit minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 16
Secondary	PGA Scores at Each Study Visit	The PGA is a clinical tool for assessing the current state/severity of a participant's psoriasis. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, plaque thickness, and scaling as guidelines. Each assessment was made as a visual 'average' of the severity of all treated areas at the time of the assessment. The scores ranged from 0 to 4 where 0 = Clear, 1 = Almost Clear, 2 = Mild, 3 = Moderate and 4=Severe. The mean of PGA scores at each study visit was summarized. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Up to Week 16
Secondary	Mean Change in PGA Score From Baseline to Each Study Visit	The PGA is a clinical tool for assessing the current state/severity of a participant's psoriasis. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, plaque thickness, and scaling as guidelines. Each assessment was made as a visual 'average' of the severity of all treated areas at the time of the assessment. The scores ranged from 0 to 4 where 0 = Clear, 1 = Almost Clear, 2 = Mild, 3 = Moderate and 4=Severe. The mean change in PGA scores from Baseline was summarized for each study visit. Baseline was defined as the latest assessment prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 16
Secondary	Mean Change in Individual Target Lesion Grading Scores From Baseline to Each Study Visit	A single target lesion of at least 3 centimeter (cm) x 3 cm was selected at Baseline. For the selected lesion, the severity of erythema, scaling and plaque thickness (induration) was assessed by the investigator on a 5-point scale ranging from 0=none to 4=severe. The mean change in individual grading scores from Baseline was summarized for each study visit. Baseline was defined as the latest assessment prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 16
Secondary	Mean Change in Weekly Average Itch/Pruritus Numeric Rating Scale (NRS) From Baseline to Each Study Visit	The participant reported itch severity was obtained from the response of the participants to the itch NRS item in the psoriasis symptom diary (PSD). PSD was developed to assess daily self-reports of psoriasis symptoms and the functional impact related to the underlying pathophysiology of the disease. The participants answered questions related to the severity and impact of the signs and symptoms daily using a 11 point NRS with scores ranging from 0 (absent) to 10 (worst imaginable). Mean change in itch/pruritis NRS from Baseline to each study visit was presented. Baseline was defined as the latest assessment prior to the first dose and change from Baseline was defined as the post dose weekly average value minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 16
Secondary	Percentage of Participants Who Achieved a PGA Score of 0 or 1 and a Minimum 2 Grade Improvement From Baseline to Each Study Visit	The PGA is a clinical tool for assessing the current state/severity of a participant's psoriasis. It is a static 5-point morphological assessment of overall disease severity, as determined by the investigator, using the clinical characteristics of erythema, plaque thickness, and scaling as guidelines. Each assessment was made as a visual 'average' of the severity of all treated areas at the time of the assessment. The scores ranged from 0 to 4 where 0 = Clear, 1 = Almost Clear, 2 = Mild, 3 = Moderate and 4=Severe. The percentage of responders that is, participants who achieved a PGA score of 0 or 1 and a minimum 2-grade improvement from baseline were summarized. Baseline was defined as the latest assessment prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 16
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs	An AE is defined as any untoward medical occurrence in a participant under clinical investigation, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. A TEAE is defined as an AE which occurred on or after study treatment start date and on or before the last visit. Number of participants with AEs and SAEs were presented. The analysis was performed on safety Population which comprised of all participants who received at least one dose of study treatment.	Up to Week 16
Secondary	Number of Participants With Reported Local Tolerability Scores	The assessment of the presence and degree of burning/stinging and itching at the application site following application of the study treatment was done at each specified study visit using a 5 point tolerability scale. The scores ranged from 0 to 4 where 0=None and 4=Strong/Severe. The score represented an average across all application sites. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Up to Week 14
Secondary	Change From Baseline in Albumin and Protein Level	Blood samples were collected for the evaluation of change in albumin and protein levels from Baseline throughout the study. Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 14
Secondary	Change From Baseline in Alkaline Phosphatase (Alk Phos), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) Levels.	Blood samples were collected for the evaluation of change in levels of alk phos, ALT, AST and GGT from Baseline throughout the study. Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 14
Secondary	Change From Baseline in Direct Bilirubin (Bil), Bilirubin (Bil), Creatinine and Urate.	Blood samples were collected for the evaluation of change in levels of direct bil, bil, creatinine and urate from Baseline throughout the study. Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 14
Secondary	Change From Baseline in Calcium, Chloride, Carbon Dioxide (CO2), Glucose, Potassium, Sodium and Urea Levels	Blood samples were collected for the evaluation of change in levels of calcium, chloride, CO2, glucose, potassium, sodium, and urea from Baseline throughout the study. Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 14
Secondary	Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets and Leukocyte Count	Blood samples were collected for the evaluation of change in levels of basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelets and leukocyte count from Baseline throughout the study. Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 14
Secondary	Change From Baseline in Hematocrit Levels	Blood samples were collected for the evaluation of change in hematocrit levels from Baseline throughout the study. Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 14
Secondary	Change From Baseline in Hemoglobin (Hgb) Level and Erythrocyte Mean Corpuscular Hgb Concentration (MCHC)	Blood samples were collected for the evaluation of change in Hgb levels and MCHC from Baseline throughout the study. Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 14
Secondary	Change From Baseline in Erythrocyte Mean Corpuscular Hemoglobin Level	Blood samples were collected for the evaluation of change in erythrocyte mean corpuscular hemoglobin level from Baseline throughout the study. Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 14
Secondary	Change From Baseline in Erythrocyte Mean Corpuscular Volume	Blood samples were collected for the evaluation of change in erythrocyte mean corpuscular volume from Baseline throughout the study. Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 14
Secondary	Change From Baseline in Erythrocyte Count	Blood samples were collected for the evaluation of change in erythrocyte count from Baseline throughout the study. Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 14
Secondary	Number of Participants With Chemistry Data of Potential Clinical Importance	Blood samples were collected for the evaluation of clinical chemistry parameters including alk phos, ALT, AST, bil, calcium, CO2, creatinine, glucose and potassium. The number of participants with chemistry data of potential clinical importance for the mentioned parameters was presented. Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Up to Week 14
Secondary	Number of Participants With Hematology Data of Clinical Importance	Blood samples were collected for the evaluation of hematology parameters including hematocrit, Hgb, lymphocytes, neutrophils and platelets. The number of participants with clinically significant abnormal values of the mentioned hematology parameters was presented. Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Up to Week 14
Secondary	Change From Baseline in Immunoglobulin (Ig) A, IgG and IgM Levels	Blood samples were collected for the evaluation of change in IgA, IgG and IgM levels from Baseline throughout the study. Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 12
Secondary	Number of Participants With Ig Data Outside the Reference Range	Blood samples were collected for the evaluation of change in Ig levels from Baseline throughout the study. Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Up to Week 12
Secondary	Number of Participants With Immunophenotyping Data Outside the Reference Range	Blood samples were collected for the evaluation of change in levels of cluster of differentiation (CD)19, CD3, CD3 Treg flow cytometry (CD3TFLC), CD3+CD8+, CD3+CD8+ TFLC, CD3+CD4+, CD3+CD4+ TFLC, CD16+CD56+, CD3+CD4+CD25+CD127 flow cytometry (CD3+CD4+CD25+CD127), CD3+CD4+foxP3+CD25+CD127 flow cytometry (CD3+CD4+fP3+CD25+CD127) and T Cell B Cell Natural Killer Lymphocytes flow cytometry (T-B cell NKL). Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Up to Week 12
Secondary	Change From Baseline in Immunophenotype Data	Blood samples were collected for the evaluation of change from Baseline in immunophenotype levels including CD19, CD3, CD3TFLC, CD3+CD8+, CD3+CD8+ TFLC, CD3+CD4+, CD3+CD4+ TFLC, CD16+CD56+, CD3+CD4+CD25+CD127 flow cytometry (CD3+CD4+CD25+CD127), CD3+CD4+foxP3+CD25+CD127 flow cytometry (CD3+CD4+fP3+CD25+CD127) and T-B cell NKL. Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 12
Secondary	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	SBP and DBP were measured in semi-supine position after at least 5 minutes of rest. Baseline was defined as the latest assessment prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 14
Secondary	Change From Baseline in Pulse Rate	Pulse rate was measured in semi-supine position after at least 5 minutes of rest. Baseline was defined as the latest assessment prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 14
Secondary	Change From Baseline in Temperature	Temperature was measured in semi-supine position after at least 5 minutes of rest. Baseline was defined as the latest assessment prior to the first dose and change from Baseline was defined as the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Baseline and up to Week 14
Secondary	Number of Participants With Vital Signs of Clinical Importance	The vital signs including SBP, DBP and pulse rate were measured from Baseline throughout the study. The number of participants with clinically significant abnormal vital signs were presented. Baseline was defined as the latest assessment prior to the first dose. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Up to Week 14
Secondary	Number of Participants With Abnormal Electrocardiogram (ECG) Findings	Single 12-lead ECGs were obtained over a brief recording period at each specified time point during the study using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT (QTc) intervals. Baseline was defined as the latest assessment (including unscheduled visits) prior to the first dose. For multiple ECGs at one visit, or "Any time post-screen", a participant is categorized as "Abnormal" if >=1 assessment is abnormal. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).	Up to Week 14