Efficacy and Safety of BMS-986165 Compared With Placebo in Participants With Active Psoriatic Arthritis (PsA)

Study Overview
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Brief Summary
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The main purpose of study is to assess the dose-response relationship of BMS-986165 (Dose A or Dose B once daily [QD]) at Week 16 in the treatment of participants with active PsA.

Detailed Description
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The study is intended to evaluate the safety and efficacy of BMS-986165 Dose A or B once daily (QD) compared with placebo in adults with active PsA. The primary endpoint is american college of rheumatology (ACR) 20 response at Week 16 (Part A).

Official Title
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A Randomized, Placebo-Controlled, Double-blind, Multicenter Study to Assess the Efficacy and Safety of Multiple Doses of BMS-986165 in Subjects With Active Psoriatic Arthritis (PsA)

Conditions
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Active Psoriatic Arthritis

Intervention / Treatment
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* Other: BMS-986165 Placebo
* Drug: BMS-986165 Dose A
* Drug: BMS-986165 Dose B
* Drug: Ustekinumab
* Other: Ustekinumab Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with PsA for at least 6 months before screening, and who meet the Classification Criteria for Psoriatic Arthritis (CASPAR) at screening Participants either (i) cannot have prior exposure to biologics (biologic-naïve) or (ii) have failed or been intolerant to 1 tumor necrosis factor -inhibitor (TNFi) (TNFi-experienced). Failure is defined as lack of response or loss of response with at least 3 months of therapy with an approved dose of a TNFi, as judged by the investigator. Failure must have occurred at least 2 months prior to Day 1 Participants have at least 1 confirmed greater than or equal to (>=) 2 centimeter (cm) lesion of plaque psoriasis at screening Participants have active arthritis as shown by a minimum of >= 3 swollen joints and >= 3 tender joints (66/68 joint counts) at screening and Day 1 High sensitivity C-reactive protein (hsCRP) >= 3milligram per liter (mg/L) at screening Women of Childbearing Potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the start of study treatment Exclusion Criteria: Has non-plaque psoriasis (that is (i.e.), guttate, inverse, pustular, erythrodermic or drug-induced psoriasis) at screening or Day 1 Has any other autoimmune condition such as rheumatoid arthritis, etc. There are exceptions for inflammatory bowel disease or uveitis as follows: currently active disease is excluded but, a history of no longer active disease for at least 12 months (including not being on medication) is allowed Has active (i.e. currently symptomatic) fibromyalgia History or evidence of active infection and/or febrile illness within 7 days prior to Day 1 (example, bronchopulmonary, urinary, gastrointestinal, etc.) History of recent serious bacterial, fungal, or viral infections requiring hospitalization and intravenous (IV) antimicrobial treatment within 90 days prior to screening, or any infection requiring antimicrobial treatment within 15 days prior to Day 1 History of active tuberculosis (TB) prior to screening visit, regardless of completion of adequate treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Part A: Placebo<br> | Other: BMS-986165 Placebo<br>* Participants will receive BMS-986165 matching placebo QD<br>|
| Experimental: Part A: BMS-986165 Dose A<br> | Drug: BMS-986165 Dose A<br>* Participants will receive BMS-986165 Dose A QD.<br>|
| Experimental: Part A: BMS-986165 Dose B<br> | Drug: BMS-986165 Dose B<br>* Participants will receive BMS-986165 dose B QD.<br>|
| Experimental: Part B: Ustekinumab + BMS-986165 Placebo<br> | Other: BMS-986165 Placebo<br>* Participants will receive BMS-986165 matching placebo QD<br>Drug: Ustekinumab<br>* Participants will receive ustekinumab SQ injection QD.<br>|
| Experimental: Part B: BMS-986165 Dose A + Ustekinumab Placebo<br> | Drug: BMS-986165 Dose A<br>* Participants will receive BMS-986165 Dose A QD.<br>Other: Ustekinumab Placebo<br>* Participants will receive ustekinumab SQ matching placebo QD<br>|
| Experimental: Part B: BMS-986165 Dose B + Ustekinumab Placebo<br> | Drug: BMS-986165 Dose B<br>* Participants will receive BMS-986165 dose B QD.<br>Other: Ustekinumab Placebo<br>* Participants will receive ustekinumab SQ matching placebo QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving the American College of Rheumatology (ACR) 20 Response at Week 16 | A participant is considered an ACR 20 responder if the following three conditions are met: 1) ≥ 20% improvement from baseline in the number of tender joints (68 joint count). 2) ≥ 20% improvement from baseline in the number of swollen joints (66 joint count). 3) ≥ 20% improvement from baseline in at least 3 of the following 5 domains: o Subject Global Assessment of disease activity o Physician Global Assessment of psoriatic arthritis o Subject Global Assessment of pain o Health Assessment Questionnaire-Disability Index (HAQ-DI) o High-sensitivity C-reactive protein (hsCRP) | 16 weeks after first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) | The HAQ-DI is measured by the use of a patient-reported outcome measure questionnaire, assessing the degree of difficulty a person has experienced during the past week in 8 domains of daily living activities. Each activity category consists of 2 to 3 questions (total of 20 questions). For reach question the level of activity is scored from 0 to 3, with 0 representing no difficulty and 3 as unable to do. Any activity that requires assistance from another individual or an assistive device adjusts to a minimum score of 2. For each activity category, the highest score reported in the 2 or 3 questions pertinent to that category represents the category score. Scores from the 8 categories are then summed and divided by 8 to generate the final score. The final score can range from 0 (most desirable outcome) to 3 (least desirable outcome). Adjusted change represents a change from baseline based on statistical model. | From baseline (day of the first dose) to 16 weeks after first dose | 
| Percentage of Participants Achieving the Psoriasis Area and Severity Index (PASI) 75 Response | The PASI is a measure of the average erythema, induration thickness and scaling of psoriatic skin lesions (each graded on a 0 to 4 scale), weighted by the area of involvement (head, arms, trunk to groin, and legs to top of buttocks). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. The PASI 75 response rate represents the percentage of participants who experienced at least a 75% improvement in PASI score as compared with the baseline value. PASI assessment was performed by trained professionals. | 16 weeks after first dose | 
| Adjusted Change From Baseline in the Physical Component Summary (PCS) Score of the Short Form Health Survey-36 (SF-36) Questionnaire | The SF-36 is a patient-reported outcome measure, which includes 36 items in a Likert-type format to measure the following 8 health dimensions over the past week: 1) limitations in physical activities, such as bathing or dressing 2) limitations in social activities because of physical or emotional problems 3) limitations in usual role activities because of physical health problems 4) bodily pain 5) general mental health (psychological distress and well-being) 6) limitations in usual role activities because of emotional problems 7) vitality (energy and fatigue) and 8) general health perceptions. The 8 health dimensions assessed are grouped into 2 main components, physical and mental. Each of the 8 dimensions contribute to both the Physical Component Summary (PCS) score and the Mental Component Summary (MCS) score. PCS and MCS scores range from 0 to 100, with high scores indicating a better health status. Adjusted change represents a change from baseline based on statistical model. | From baseline (day of the first dose) to 16 weeks after first dose | 
| Percentage of Participants Achieving the American College of Rheumatology (ACR) 50 Response at Week 16 | A participant is considered an ACR 50 responder if the following three conditions are met: 1) ≥ 50% improvement from baseline in the number of tender joints (68 joint count). 2) ≥ 50% improvement from baseline in the number of swollen joints (66 joint count). 3) ≥ 50% improvement from baseline in at least 3 of the following 5 domains: o Subject Global Assessment of disease activity o Physician Global Assessment of psoriatic arthritis o Subject Global Assessment of pain o Health Assessment Questionnaire-Disability Index (HAQ-DI) o High-sensitivity C-reactive protein (hsCRP) | 16 weeks after first dose | 
| Percentage of Participants Achieving the American College of Rheumatology (ACR) 70 Response at Week 16 | A participant is considered an ACR 70 responder if the following three conditions are met: 1) ≥ 70% improvement from baseline in the number of tender joints (68 joint count). 2) ≥ 70% improvement from baseline in the number of swollen joints (66 joint count). 3) ≥ 70% improvement from baseline in at least 3 of the following 5 domains: o Subject Global Assessment of disease activity o Physician Global Assessment of psoriatic arthritis o Subject Global Assessment of pain o Health Assessment Questionnaire-Disability Index (HAQ-DI) o High-sensitivity C-reactive protein (hsCRP) | 16 weeks after first dose | 
| Percentage of Participants Achieving Low Disease Activity According to the Disease Activity Score-28 Using C Reactive Protein (DAS 28 CRP) | A Disease Activity Score (DAS) is a scoring system used to assess disease activity. DAS 28 CRP is a composite outcome measure that assesses: • How many joints in the hands (including metacarpophalangeal and proximal interphalangeal joints, but excluding distal interphalangeal joints), wrists, elbows, shoulders, and knees are swollen and/or tender over a total of 28. • C Reactive Protein (CRP) levels in the blood (as a measure of the degree of inflammation) • Subject Global Assessment of disease activity The results are combined to produce the DAS 28 CRP score, which correlates with the extent of disease activity as follows: • < 2.6: Disease remission • 2.6 - 3.2: Low disease activity • 3.2 - 5.1: Moderate disease activity • > 5.1: High disease activity. Only participants with a score < 3.2 are considered to have achieved low disease activity. | 16 weeks after first dose | 
| Percentage of Participants Achieving Remission According to the Disease Activity Score-28 Using C Reactive Protein (DAS 28 CRP) | A Disease Activity Score (DAS) is a scoring system used to assess disease activity. DAS 28 CRP is a composite outcome measure that assesses: • How many joints in the hands (including metacarpophalangeal and proximal interphalangeal joints, but excluding distal interphalangeal joints), wrists, elbows, shoulders, and knees are swollen and/or tender over a total of 28. • C Reactive Protein (CRP) levels in the blood (as a measure of the degree of inflammation) • Subject Global Assessment of disease activity The results are combined to produce the DAS 28 CRP score, which correlates with the extent of disease activity as follows: • < 2.6: Disease remission • 2.6 - 3.2: Low disease activity • 3.2 - 5.1: Moderate disease activity • > 5.1: High disease activity. Only participants with a score < 2.6 are considered to have achieved remission. | 16 weeks after first dose | 
| Adjusted Change From Baseline in the Disease Activity Score-28 Using C Reactive Protein (DAS 28 CRP) Score | A Disease Activity Score (DAS) is a scoring system used to assess disease activity. DAS 28 CRP is a composite outcome measure that assesses: • How many joints in the hands (including metacarpophalangeal and proximal interphalangeal joints, but excluding distal interphalangeal joints), wrists, elbows, shoulders, and knees are swollen and/or tender over a total of 28. • C Reactive Protein (CRP) levels in the blood (as a measure of the degree of inflammation) • Subject Global Assessment of disease activity The results are combined to produce the DAS 28 CRP score, which correlates with the extent of disease activity as follows: • < 2.6: Disease remission • 2.6 - 3.2: Low disease activity • 3.2 - 5.1: Moderate disease activity • > 5.1: High disease activity. Adjusted change represents a change from baseline based on statistical model. | From baseline (day of first dose) to 16 weeks after first dose | 
| Adjusted Change From Baseline in Dactylitis Count | The number of digits in hands and feet with dactylitis (Tender + Non-Tender) was counted and change from baseline at week 16 was assessed. Adjusted change represents a change from baseline based on statistical model. | From baseline (day of first dose) to 16 weeks after first dose | 
| Adjusted Change From Baseline in the Leeds Dactylitis Index (LDI) Basic Score | The Leeds Dactylitis Index (LDI) Basic is a quantitative measurement of dactylitis in the 20 digits using a dactylometer. The circumference of the affected and contralateral digits, and tenderness of the affected digits are measured to generate a total score. For each dactylitic digit, the final score is defined as: [{(A/B) - 1}*100]*C, where A is circumference of involved digit, B is circumference of the opposite, unaffected, digit or reference, and C is tenderness (0 or 1). The total score is determined by summing the relative score of all digits. A higher score indicates worse dactylitis. Adjusted change represents a change from baseline based on statistical model. | From baseline (day of first dose) to 16 weeks after first dose | 
| Percentage of Participants Achieving Dactylitis Resolution | Dactylitis resolution (tender digits only) is defined as a dactylitis count of 0 in participants with dactylitis count ≥ 1 at baseline | 16 weeks after first dose | 
| Adjusted Change From Baseline in Enthesitis by the Leeds Enthesitis Index (LEI) | The LEI was developed specifically for psoriatic arthritis. An overall score of 0 to 6 is derived from the presence or absence of tenderness at 6 entheseal sites (right and left: lateral epicondyle, medial femoral condyle, and Achilles tendon insertion) at the time of evaluation. A higher count indicates a greater enthesitis burden. Adjusted change represents a change from baseline based on statistical model. | From baseline (day of first dose) to 16 weeks after first dose | 
| Adjusted Change From Baseline in Enthesitis by the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index | The SPARCC Enthesitis Index has a 0 to 16 score that is derived from the evaluation of 8 locations: the greater trochanter (R/L), quadriceps tendon insertion into the patella (R/L), patellar ligament insertion into the patella and tibial tuberosity (R/L), Achilles tendon insertion (R/L), plantar fascia insertion (R/L), medial and lateral epicondyles (R/L), and the supraspinatus insertion (R/L). A higher count indicates a higher enthesitis burden based on the current evaluation. Adjusted change represents a change from baseline based on statistical model. | From baseline (day of first dose) to 16 weeks after first dose | 
| Percentage of Participants Achieving Enthesitis Resolution by the Leeds Enthesitis Index (LEI) | The LEI was developed specifically for psoriatic arthritis. An overall score of 0 to 6 is derived from the presence or absence of tenderness at 6 entheseal sites (right and left: lateral epicondyle, medial femoral condyle, and Achilles tendon insertion) at the time of evaluation. A higher count indicates a greater enthesitis burden. Enthesitis resolution is defined as s LEI score of 0, in subjects with LEI ≥ 1 at baseline | 16 weeks after first dose | 
| Percentage of Participants Achieving Enthesitis Resolution by the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index | The SPARCC Enthesitis Index has a 0 to 16 score that is derived from the evaluation of 8 locations: the greater trochanter (R/L), quadriceps tendon insertion into the patella (R/L), patellar ligament insertion into the patella and tibial tuberosity (R/L), Achilles tendon insertion (R/L), plantar fascia insertion (R/L), medial and lateral epicondyles (R/L), and the supraspinatus insertion (R/L). A higher count indicates a higher enthesitis burden based on the current evaluation. Enthesitis resolution defined as a SPARCC enthesitis index score of 0, in subjects with SPARCC ≥ 1 at baseline. | 16 weeks after first dose | 
| Percentage of Participants Achieving a Physicians Global Assessment-Fingernails (PGA-F) Score of 0 or 1 | In participants with psoriasis fingernail involvement, the PGA-F score is used to evaluate the overall condition of the fingernails in terms of disease severity. The assessment is performed by the investigator, who rates the fingernail condition on a 5-point scale based on the higher of the nail bed/nail matrix score. Scores are 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe). | 16 weeks after first dose | 
| Percentage of Participants Achieving Minimal Disease Activity (MDA) Response | A Minimal Disease Activity (MDA) responder is defined as a participant fulfilling 5 of the following 7 outcomes: • Tender joint count ≤ 1 • Swollen joint count ≤ 1 • Psoriasis Area and Severity Index (PASI) ≤ 1 or body surface area (BSA) ≤ 3% • Subject Global Assessment of pain ≤ 15 • Subject Global Assessment of disease activity ≤ 20 • Health Assessment Questionnaire-Disability Index (HAQ-DI) ≤ 0.5 • Tender entheseal points ≤ 1 | 16 weeks after first dose | 
| Adjusted Change From Baseline in the Psoriatic Arthritis Disease Activity Score (PASDAS) | PASDAS is a composite measure calculated from the Physician Global Assessment of psoriatic arthritis, the Subject Global Assessment of disease activity, the Short Form Health Survey-36 Item (SF-36) Physical Component Summary (PCS), the swollen joint count, the tender joint count, the Leeds Enthesitis Index (LEI), the Leeds Dactylitis Index (LDI) (Basic), and the the levels of high-sensitivity C-reactive Protein (hsCRP). Each item contributes differently to the final score, which ranges from 0 to 10 (higher scores represent a higher level of disease activity). Adjusted change represents a change from baseline based on statistical model. | From baseline (day of first dose) to 16 weeks after first dose | 
| Adjusted Change From Baseline in the Disease Activity Index for Psoriatic Arthritis Score (DAPSA) | DAPSA is a composite measure to assess peripheral joint involvement that is based upon numerical summation of 5 variables of disease activity: tender/painful joint count 68, swollen joint count 66, Subject Global Assessment of disease activity, Subject Global Assessment of pain, and the levels of C-reactive Protein (CRP). Final scores are interpreted as follows: - ≤4 = Remission (REM) - > 4 and ≤ 28 = moderate disease activity (MDA) - >28 = high disease activity (HDA). Adjusted change represents a change from baseline based on statistical model. | From baseline (day of first dose) to 16 weeks after first dose | 
| Percentage of Participants Achieving Psoriatic Arthritis Response Criteria (PsARC) | PsARC consists of 4 measurements: tender/painful joint count, swollen joint count, Physician Global Assessment of psoriatic arthritis, and Subject Global Assessment of pain ≤ 15. In order to be classified as a PsARC responder, participants must achieve improvement in 2 of 4 measures, one of which must be joint pain or swelling, without worsening in any measure. | 16 weeks after first dose | 
| Adjusted Change From Baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) | In participants with baseline evidence of Psoriatic Arthritis Spondylitis, symptoms are evaluated using the BASDAI, which consists of a 0 to 100 scale measuring discomfort, pain, and fatigue in response to 6 questions pertaining to the 5 major symptoms of ankylosing spondylitis: • Fatigue (medical) • Spinal pain • Joint pain and swelling • Areas of localized tenderness • Morning stiffness duration • Morning stiffness severity A higher count indicates worse disease. Adjusted change represents a change from baseline based on statistical model. | From baseline (day of first dose) to 16 weeks after first dose | 
| Adjusted Change From Baseline in the Mental Component Summary (MCS) Score of the Short Form Health Survey-36 (SF-36) Questionnaire | The SF-36 is a patient-reported outcome measure, which includes 36 items in a Likert-type format to measure the following 8 health dimensions over the past week: 1) limitations in physical activities, such as bathing or dressing 2) limitations in social activities because of physical or emotional problems 3) limitations in usual role activities because of physical health problems 4) bodily pain 5) general mental health (psychological distress and well-being) 6) limitations in usual role activities because of emotional problems 7) vitality (energy and fatigue) and 8) general health perceptions. The 8 health dimensions assessed are grouped into 2 main components, physical and mental. Each of the 8 dimensions contribute to both the Physical Component Summary (PCS) score and the Mental Component Summary (MCS) score. PCS and MCS scores range from 0 to 100, with high scores indicating a better health status. Adjusted change represents a change from baseline based on statistical model. | From baseline (day of the first dose) to 16 weeks after first dose | 
| Adjusted Change From Baseline in the Psoriatic Arthritis Impact of Disease (PsAID) 12 Score | PsAID is a 12-item self-report that measures psoriatic arthritis symptoms and impact of disease. Each item is scored on a 0 to 10 numeric rating scale, and each item contributes differently to the final score. Weighted scores for each item are summed and divided by 20 to generate the final score, ranging from 0 to 10 (higher values indicate worse health). Adjusted change represents a change from baseline based on statistical model. | From baseline (day of the first dose) to 16 weeks after first dose | 
| Adjusted Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score | The FACIT-Fatigue instrument is a questionnaire used to evaluate a range of self-reported symptoms over the past week, from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. Fatigue is divided into the experience of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities. The questionnaire is composed of 13 questions (Short Form 13a) and each question is scored from 1 to 5. The final score results from the sum of the scores of the 13 questions, and ranges from 13 (most desirable outcome) to 65 (least desirable outcome). Adjusted change represents a change from baseline based on statistical model. | From baseline (day of the first dose) to 16 weeks after first dose | 
| Adjusted Change From Baseline in the Work Limitation Questionnaire (WLQ) Score | The Work Limitation Questionnaire (WLQ) is a 25-item self-report that measures the on-the-job impact of chronic health conditions and treatment over the past 2 weeks. It focuses on assessing limitations while performing specific job demands from the following 4 domains: 1) Time management: difficulty with handling time and scheduling demands (5 items) 2) Physical demands: ability to perform job tasks that involve bodily strength, movement, endurance, coordination, and flexibility (6 items) 3) Mental-interpersonal demands: cognitively demanding tasks and on-the-job social interactions (9 items) 4) Output demands: concerns reduced work productivity (5 items). Final score ranges from 0 (limited none of the time) to 100 (limited all of the time). The score can be used to calculate a percent of lost work productivity due to a particular disease state. Adjusted change represents a change from baseline based on statistical model. | From baseline (day of the first dose) to 16 weeks after first dose | 
| Percentage of Participants Achieving Health Assessment Questionnaire-Disability Index (HAQ-DI) 0.35 Response | The HAQ-DI is measured by the use of a patient-reported outcome measure questionnaire, assessing the degree of difficulty a person has experienced during the past week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consists of 2 to 3 questions (total of 20 questions). For reach question the level of activity is scored from 0 (no difficulty) to 3 (unable to do). For each activity category, the highest score reported in the 2 or 3 questions pertinent to that category represents the category score. Scores from the 8 categories are then summed and divided by 8 to generate the final score. The final score can range from 0 (most desirable outcome) to 3 (least desirable outcome). A HAQ-DI 0.35 responder is defined as a participant with an improvement from baseline in HAQ-DI score of at least 0.35. | 16 weeks after first dose | 
| Percentage of Participants Achieving the Psoriasis Area and Severity Index (PASI) 90 Response | The PASI is a measure of the average erythema, induration thickness and scaling of psoriatic skin lesions (each graded on a 0 to 4 scale), weighted by the area of involvement (head, arms, trunk to groin, and legs to top of buttocks). The PASI produces a numeric score that can range from 0 to 72, with higher PASI scores denoting more severe disease activity. The PASI 90 response rate represents the percentage of participants who experienced at least a 90% improvement in PASI score as compared with the baseline value. PASI assessment was performed by trained professionals. | 16 weeks after first dose | 
| Change From Baseline in Electrocardiogram (ECG) Results |  | From baseline (day of first dose) to 16 weeks after first dose | 
| Change From Baseline in Electrocardiogram (ECG) Heart Rate |  | From baseline (day of first dose) to 16 weeks after first dose | 
| Change From Baseline in Vital Signs - Diastolic Blood Pressure |  | From baseline (day of first dose) to 16 weeks after first dose | 
| Change From Baseline in Vital Signs - Heart Rate |  | From baseline (day of first dose) to 16 weeks after first dose | 
| Change From Baseline in Vital Signs - Respiratory Rate |  | From baseline (day of first dose) to 16 weeks after first dose | 
| Change From Baseline in Vital Signs - Systolic Blood Pressure |  | From baseline (day of first dose) to 16 weeks after first dose | 
| Change From Baseline in Vital Signs - Temperature |  | From baseline (day of first dose) to 16 weeks after first dose | 
| Change From Baseline in Vital Signs - Weight |  | From baseline (day of first dose) to 16 weeks after first dose |