IgA Nephropathy, IgAN - IgA Nephropathy, Immunoglobulin A Nephropathy
Conditions
Keywords
chronic glomerular disease, autoimmune glomerulonephritis
Brief summary
This is a phase 1, randomized, placebo-controlled, double-blind, single ascending dose study of IV VIS649 in healthy subjects. VIS649 is a monoclonal immunoglobulin G2 (IgG2) antibody targeting the B-cell growth factor APRILL. The study will enroll up to 45 subjects and will be conducted in up to 5 sequential dosing cohorts at four different dose levels, enrolling 9 subjects per cohort. Subjects will be randomized to VIS649 or placebo in a ratio of 7:2 (7 active, 2 placebo). Safety, pharmacokinetic (PK) and pharmacodynamic (PD) data from the initial cohorts will be assessed.
Detailed description
On Day 1, a single dose of VIS649 or placebo will be administered IV. Pharmacokinetics sampling will start with a collection prior to the start of infusion and at multiple timepoints throughout the study. Pharmacodynamics sampling will occur at baseline and multiple timepoints throughout the study. Sentinel subjects will be utilized; the first two subjects in each cohort will be randomized to receive either VIS649 or placebo and will receive study drug at least 24 hours before the remaining subjects in the cohort are dosed. The safety profile of these subjects over the 24 hour post-administration period will be reviewed to determine whether it is appropriate to proceed with enrollment of the remaining subjects in the cohort as planned. This will occur for each dose escalation. The maximum duration of participation (Screening through End-of-study) for individual subjects will be approximately 20 weeks (5 months). The scheduled final visit will occur 16 weeks post-dosing (112 days).
Interventions
BIOLOGICALVIS649
Single IV dose of study product on Day 1 of study
BIOLOGICALPlacebo
Singe IV dose of placebo administered via IV on Day 1 of study
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The clinical study will be performed in a double-blind manner, for clinical research unit staff interacting with study participants, with the exception of the persons involved in the preparation of the IMPs. These persons will not be involved in any other study activities.
Intervention model description
phase 1, randomized, placebo-controlled, double-blind, single ascending dose study
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Subject voluntarily agrees to participate in this study and signs an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form prior to performing any of the Screening Visit procedures and be able to sign and date an appropriate Health Insurance Portability and Accountability Act (HIPAA) authorization form or subject privacy form, if appropriate. 2. Male and female subjects between 18 to 55 years of age, inclusive, at the Screening Visit. 3. For Japanese subjects: Subject is of Japanese descent as evidenced by verbal confirmation of familial heritage (a subject has all four Japanese grandparents born in Japan). 4. For non-Japanese subjects: Subjects must be of non-Asian descent, as evidenced by verbal confirmation that all four grandparents are non-Asian. 5. The following applies to female subjects: * Non-childbearing potential (surgically sterile \[hysterectomy or bilateral tubal ligation\]) for at least 6 months, or postmenopausal ≥ 1 year, or * Non-pregnant, non-lactating females of childbearing potential must report prior use (over the 28 days prior to dosing of study drug) of medically acceptable forms of birth control (hormonal contraception, abstinence, diaphragm with spermicide, condom with spermicide or intrauterine device, or partner with vasectomy), with agreement to continue to use a medically acceptable form of birth control (as described) through the end of their participation in the study. Alternatively, a reported history of abstinence beginning at least 28 days prior to study drug dosing, with agreement to continue abstinence through the end of their participation in the study are required. Females of childbearing potential must also have a negative serum human chorionic gonadotropin (hCG) pregnancy test at Screening and a negative urine hCG pregnancy test at Baseline (Day -1). Female subjects must also agree not to donate eggs/bank eggs for the duration of their participation in the study. 6. For male, subject and/or his partner must use a highly effective form of contraception (i.e., double-barrier as described above, have had a vasectomy, or have a female partner of non childbearing potential) or agree to abstinence following study drug dosing, through the end of the subject's participation in the study. Male subjects must also agree to not donate sperm for the duration of their participation in the study, following study drug dosing. 7. Screening laboratory values must meet the following criteria: * White blood cells 3,000 12,000/mm3 * Platelets \>150,000/mm3 * Hemoglobin \>13 gm/dL for male and\>11 gm/dL for female * Estimated glomerular filtration rate \>80 mL/min/1.73 m2 * Serum creatinine \<1.25x Upper Limit of Normal (ULN) * Blood Urea Nitrogen (BUN) ≤25mg/dL * Aspartate aminotransferase (AST) ≤50 U/L * Alanine aminotransferase (ALT) ≤67 U/L * Alkaline phosphatase ≤150 U/L * Total Bilirubin ≤1.4 mg/dL unless patient has Gilbert Syndrome, in which case direct bilirubin must be within normal range * Glucose (fasting) \<115 mg/dL * Drug and alcohol screen Negative * Serum Immunoglobulin G (IgG) \>750 mg/dL (7.5 g/L) * Serum Immunoglobulin M (IgM) \>55 mg/dL (0.55 g/L) * Serum IgA \>80 mg/dL (0.8 g/L) 8. Body mass index (BMI) between 18 and 32 kg/m2, inclusive, at the Screening Visit. 9. Healthy, determined by pre-study medical evaluation (medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory evaluations), as judged by the Investigator. 10. Is willing and able to comply with study restrictions and to remain at the central processing unit (CPU) for the in-patient duration of the study and return for all follow-up outpatient visits. 11. QTcF or QTcB \< 450 msec at Screening (may be repeated once).
Exclusion criteria
1. Is participating in another clinical study of any investigational drug, device, or intervention or has received any investigational medication during the last 30 days or five half-lives, whichever is longer, before Baseline (Day -1). 2. Subject is judged by the Investigator or the Medical Monitor to be inappropriate for the study. 3. Subject has a history or current evidence of a serious and/or unstable cardiovascular, respiratory, gastrointestinal, hematologic, autoimmune, blood dyscrasias or other medical disorder, including psychiatric disorders, cirrhosis or malignancy. History of minor skin cancers (not including melanoma) or surgically treated, limited cervical carcinomas (i.e., carcinoma in situ) are not exclusionary. 4. Subject has a history or presence of proteinuria, chronic kidney disease, disease requiring immunosuppressive therapy (including systemic steroids), or is considered to be immunosuppressed for any other reason. 5. Previous receipt of antibody or biologic therapy whether licensed or investigational (immunoglobulin products, monoclonal antibodies or antibody fragments) within 30 days prior to dosing or 5 half-lives within the dose of Investigational medicinal products (IMP), whichever is longer. 6. History of a previous severe allergic reaction with generalized urticaria; angioedema or anaphylaxis. 7. Blood pressure \>160/100 mmHg or \<90/50 mmHg (may be repeated once if abnormal), at the Screening visit and Day 1. 8. Known hypoglobulinemia disorder (i.e., common variable immunodeficiency), X linked agammaglobulinemia, selective IgA deficiency, selective IgM deficiency). 9. History of pre-existing latent infections (e.g., tuberculosis) or any infection requiring hospitalization or treatment with antivirals or antibiotics, or vaccination within 30 days prior to administration of study medication. 10. Concomitant use of marketed or investigational systemic immunosuppressive or immunomodulatory medications (e.g., corticosteroids, methotrexate, azathioprine, etc. and/or biologics) is prohibited and require a washout period prior to Screening (30 days or 5 half lives, whichever is longer). 11. Has received any prescription or non-prescription (over-the-counter \[OTC\]) except acetaminophen or ibuprofen, including hormonal contraceptives, topical medications, vitamins, dietary or herbal during the last 30 days or 5 half-lives, whichever is longer, preceding Baseline (Day -1). 12. Subjects who consume more than 21 units of alcohol per week (7 days) or those who have a history of alcohol or drug/chemical abuse; one unit of alcohol is equivalent to eight ounces of beer, 4 ounces of wine, or one ounce of spirits. 13. Subject is a user or former user of nicotine-containing products (including but not limited to cigarettes, cigars, and chewing or dipping tobacco) who stopped use or consumption (i.e., smoking, chewing, or pinching) of these nicotine-containing products less than 3 months before study drug administration or is using or has used topical or oral nicotine preparations for smoking cessation within the past 90 days before study drug administration. 14. Subjects who consume greater than 500 mg of caffeine or xanthine-containing products per day (e.g., coffee, tea, soft drinks, energy drinks, or chocolate). 15. Subjects who refuse to abstain from alcohol, xanthine-containing or caffeine-containing foods or beverages, or grapefruit foods or beverages, or Seville-orange containing foods (e.g., orange marmalade) or beverages, from 48 hours prior to check-in on Day-1 through the end of the study. 16. Subjects with a positive urine drug (inclusive of marijuana) or alcohol Screening test result at Screening and Day -1. 17. Subjects with a positive hepatitis B surface antigen test or evidence of chronic hepatitis C virus (HCV) infection at Screening (a negative HCV antibody assay at screening is sufficient to rule-out chronic HCV infection for this study). 18. Subjects with a known history of a positive Human Immunodeficiency Virus (HIV) or a positive test result at Screening. 19. Subjects who have donated \>500 mL or blood within 60 days prior to start of Screening. 20. The subject has donated any plasma within 7 days prior to Baseline (Day -1). 21. Is an employee of the clinical research team (any Visterra or research site employee), or has a family member who is an employee of these organizations.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Summary of Treatment Emergent Adverse Events | Baseline to day 112 | The number adverse events (AEs), serious adverse events (SAEs), and drug related events following administration of VIS649. Safety will be assessed via AE severity per CTCAE v4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. | The maximum serum concentration (Cmax) of VIS649 determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants |
| Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participant | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. | The time to the maximum serum concentration (tmax) of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants |
| The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. | Summary of the pharmacokinetic profiles of VIS649 exposure in serum for all participants. AUC0-112 presents the area under the concentration time curve from pre-dose (time 0) to the concentration on day 112. AUC0-last presents the area under the concentration time curve from pre-dose (time 0) to the last quantifiable concentration. AUC0-inf presents the area under the concentration time curve from pre-dose (time 0) extrapolated to infinite time. |
| T 1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. | The terminal elimination half life (t1/2) of VIS649 from the concentration-time profile as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. |
| CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. | Day 1 to day 112 | The clearance rate (CL) of VIS649 using the exposure calculated to infinity of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants. |
| Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants | Day 1 to day 112 | The volume of distribution of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants. |
| Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Time Profile. Japanese Participants | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. | The maximum serum concentration (Cmax) of VIS649 determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. Japanese participants |
| Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Japanese Participants | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. | The time to the maximum serum concentration (tmax) of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. Japanese participants. |
| The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Japanese Participants | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. | AUC0-112 presents the area under the concentration time curve from pre-dose (time 0) to the concentration on day 112. AUC0-last presents the area under the concentration time curve from pre-dose (time 0) to the last quantifiable concentration. AUC0-inf presents the area under the concentration time curve from pre-dose (time 0) extrapolated to infinite time. |
| T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. Japanese Participants | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. | The terminal elimination half life (t1/2) of VIS649 from the concentration-time profile as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. |
| CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. Japanese Participants | Day 1 to day 112. | The clearance rate (CL) of VIS649 using the exposure calculated to infinity of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. |
| Vd: The Volume of Distribution of VIS649 in Serum Samples. Japanese Participants | Day 1 to day 112. | The volume of distribution of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. |
| Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Non-Japanese Participants | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. | The maximum serum concentration (Cmax) of VIS649 determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. |
| Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Non-Japanese Participants | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. | The time to the maximum serum concentration (tmax) of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. |
| The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. | Summary of the pharmacokinetic profiles of VIS649 exposure in serum for non-Japanese participants. AUC0-112 presents the area under the concentration time curve from pre-dose (time 0) to the concentration on day 112. AUC0-last presents the area under the concentration time curve from pre-dose (time 0) to the last quantifiable concentration. AUC0-inf presents the area under the concentration time curve from pre-dose (time 0) extrapolated to infinite time. |
| T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. Non-Japanese Participants | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. | The terminal elimination half life (t1/2) of VIS649 from the concentration-time profile as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. Non-Japanese participants. |
| CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. Non-Japanese Participants | Day 1 to day 112. | The clearance rate (CL) of VIS649 using the exposure calculated to infinity of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. |
| Vd: The Volume of Distribution of VIS649 in Serum Samples. Non-Japanese Participants | Day 1 to day 112. | The volume of distribution of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. |
| Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | From baseline to Week 24 | The effect of VIS649 treatment on total IgG levels in serum, weekly observations from baseline to Week 24 |
| Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | From baseline to Week 24 | The effect of VIS649 treatment on total IgA levels in serum, weekly observations from Baseline to Week 24 |
| Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | From baseline to Week 24 | The effect of VIS649 treatment on total IgM levels in serum, weekly observations from Baseline to Week 24 |
| Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | From baseline to Week 24 | The effect of VIS649 treatment on the population of circulating CD16 +CD56 (Natural killer) cells in serum for all participants in cohorts 1-4. |
| Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | From baseline to Week 24 | The effect of VIS649 treatment on the population of circulating CD19 (B Cells) in serum for all participants in cohorts 1-4. |
| Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | From baseline to Week 24 | The effect of VIS649 treatment on the population of circulating CD4 T cells in serum for all participants in cohorts 1-4. |
| Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | From baseline to Week 24 | The effect of VIS649 treatment on the population of circulating CD3 T cells in serum for all participants in cohorts 1-4. |
| Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | From baseline to Week 24 | The effect of VIS649 treatment on the population of circulating CD8 T cells in serum for all participants in cohorts 1-4. |
| Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Baseline to Day 112 | Summary of Anti -VIS649 anti-drug antibodies (ADA) by treatment group, all participants |
| Summary of Anti -VIS649 Antibody (ADA) Titer by Treatment | Baseline to Day 112 | Summary of Anti -VIS649 antibody (ADA) titer by treatment, all participants with ADA positive results |
| Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. | The maximum serum concentration (Cmax) of VIS649 determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants by anti-VIS649 status (positive or negative). |
| Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. | The time to the maximum serum concentration (tmax) of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants by anti-VIS649 status (positive or negative). |
| The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. | Summary of the pharmacokinetic profiles of VIS649 exposure in serum for all participants based on their anti-VIS649 antibody status (negative/positive). AUC0-112 presents the area under the concentration time curve from pre-dose (time 0) to the concentration on day 112. AUC0-last presents the area under the concentration time curve from pre-dose (time 0) to the last quantifiable concentration. AUC0-inf presents the area under the concentration time curve from pre-dose (time 0) extrapolated to infinite time. |
| T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status. | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. | The terminal elimination half life (t1/2) of VIS649 from the concentration-time profile as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants by anti-VIS649 antibody status (negative/positive). |
| CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. All Participants by Anti-VIS649 Antibody Status. | 112 days | The clearance rate (CL) of VIS649 using the exposure calculated to infinity of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants by anti-VIS649 antibody status (positive or negative).. |
| Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status (Positive or Negative) | 112 days | The calculated volume of distribution of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants by anti-VIS649 antibody status (positive or negative). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATOREsther Yoon, MD
Parexel
Participant flow
Recruitment details
Recruitment was done for a single clinical site.
Pre-assignment details
No notable events took place between participant enrollment and assignment.
Participants by arm
| Arm | Count |
|---|---|
| Pooled Placebo Single IV dose of placebo will be administered via IV over approximately 1 hour on Day 1. | 8 |
| VIS649 Cohort 1 A single dose (0.5 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. | 7 |
| VIS649 Cohort 2 A single dose (2.0 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. | 7 |
| VIS649 Cohort 3 A single dose (6.0 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. | 7 |
| VIS649 Cohort 4 A single dose (12 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. | 7 |
| Placebo Cohort 5 + Vaccine Single dose of placebo followed by single dose of vaccine | 5 |
| VIS649 Cohort 5 + Vaccine Single dose of 6.0 mg/kg VIS649 followed by single dose of vaccine | 10 |
| Total | 51 |
Baseline characteristics
| Characteristic | VIS649 Cohort 1 | Total | VIS649 Cohort 5 + Vaccine | Placebo Cohort 5 + Vaccine | VIS649 Cohort 4 | VIS649 Cohort 3 | Pooled Placebo | VIS649 Cohort 2 |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 29.4 years STANDARD_DEVIATION 6.7 | 35.3 years STANDARD_DEVIATION 9.99 | 30.9 years STANDARD_DEVIATION 7.28 | 33.4 years STANDARD_DEVIATION 8.44 | 40.9 years STANDARD_DEVIATION 11.87 | 41.0 years STANDARD_DEVIATION 9.63 | 32.6 years STANDARD_DEVIATION 9.24 | 40.4 years STANDARD_DEVIATION 11.7 |
| Body Mass Index | 25.39 kg/m2 STANDARD_DEVIATION 2.812 | 24.67 kg/m2 STANDARD_DEVIATION 3.145 | 24.52 kg/m2 STANDARD_DEVIATION 2.011 | 25.52 kg/m2 STANDARD_DEVIATION 2.906 | 24.00 kg/m2 STANDARD_DEVIATION 2.864 | 24.86 kg/m2 STANDARD_DEVIATION 4.156 | 25.10 kg/m2 STANDARD_DEVIATION 4.275 | 23.96 kg/m2 STANDARD_DEVIATION 3.625 |
| Height (cm) | 165.4 cm STANDARD_DEVIATION 10.11 | 168.7 cm STANDARD_DEVIATION 10.64 | 174.9 cm STANDARD_DEVIATION 11.82 | 167.8 cm STANDARD_DEVIATION 10.33 | 167.1 cm STANDARD_DEVIATION 13.04 | 166.4 cm STANDARD_DEVIATION 7.93 | 170.9 cm STANDARD_DEVIATION 8.22 | 165.3 cm STANDARD_DEVIATION 11.91 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 16 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 22 Participants | 7 Participants | 3 Participants | 3 Participants | 1 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 13 Participants | 3 Participants | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 7 participants | 51 participants | 10 participants | 5 participants | 7 participants | 7 participants | 8 participants | 7 participants |
| Sex: Female, Male Female | 5 Participants | 29 Participants | 4 Participants | 3 Participants | 4 Participants | 5 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 2 Participants | 22 Participants | 6 Participants | 2 Participants | 3 Participants | 2 Participants | 5 Participants | 2 Participants |
| Weight (kg) | 69.64 Kg STANDARD_DEVIATION 11.563 | 70.60 Kg STANDARD_DEVIATION 12.097 | 74.33 Kg STANDARD_DEVIATION 10.624 | 71.36 Kg STANDARD_DEVIATION 4.225 | 67.24 Kg STANDARD_DEVIATION 12.699 | 70.03 Kg STANDARD_DEVIATION 11.517 | 73.53 Kg STANDARD_DEVIATION 15.378 | 66.3 Kg STANDARD_DEVIATION 16.236 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 5 | 0 / 10 |
| other Total, other adverse events | 4 / 8 | 2 / 7 | 3 / 7 | 3 / 7 | 3 / 7 | 3 / 5 | 4 / 10 |
| serious Total, serious adverse events | 0 / 8 | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 7 | 0 / 5 | 0 / 10 |
Outcome results
Primary
Overall Summary of Treatment Emergent Adverse Events
The number adverse events (AEs), serious adverse events (SAEs), and drug related events following administration of VIS649. Safety will be assessed via AE severity per CTCAE v4.0
Time frame: Baseline to day 112
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pooled Placebo | Overall Summary of Treatment Emergent Adverse Events | Moderate severity | 0 Event |
| Pooled Placebo | Overall Summary of Treatment Emergent Adverse Events | Adverse Events | 8 Event |
| Pooled Placebo | Overall Summary of Treatment Emergent Adverse Events | Mild severity | 4 Event |
| Pooled Placebo | Overall Summary of Treatment Emergent Adverse Events | Drug related events | 3 Event |
| Pooled Placebo | Overall Summary of Treatment Emergent Adverse Events | Serious Adverse Events | 0 Event |
| Pooled Placebo | Overall Summary of Treatment Emergent Adverse Events | Severe severity | 0 Event |
| VIS649 Cohort 1 | Overall Summary of Treatment Emergent Adverse Events | Serious Adverse Events | 0 Event |
| VIS649 Cohort 1 | Overall Summary of Treatment Emergent Adverse Events | Adverse Events | 3 Event |
| VIS649 Cohort 1 | Overall Summary of Treatment Emergent Adverse Events | Moderate severity | 0 Event |
| VIS649 Cohort 1 | Overall Summary of Treatment Emergent Adverse Events | Mild severity | 2 Event |
| VIS649 Cohort 1 | Overall Summary of Treatment Emergent Adverse Events | Drug related events | 2 Event |
| VIS649 Cohort 1 | Overall Summary of Treatment Emergent Adverse Events | Severe severity | 0 Event |
| VIS649 Cohort 2 | Overall Summary of Treatment Emergent Adverse Events | Adverse Events | 7 Event |
| VIS649 Cohort 2 | Overall Summary of Treatment Emergent Adverse Events | Serious Adverse Events | 0 Event |
| VIS649 Cohort 2 | Overall Summary of Treatment Emergent Adverse Events | Drug related events | 3 Event |
| VIS649 Cohort 2 | Overall Summary of Treatment Emergent Adverse Events | Mild severity | 2 Event |
| VIS649 Cohort 2 | Overall Summary of Treatment Emergent Adverse Events | Moderate severity | 0 Event |
| VIS649 Cohort 2 | Overall Summary of Treatment Emergent Adverse Events | Severe severity | 1 Event |
| VIS649 Cohort 3 | Overall Summary of Treatment Emergent Adverse Events | Drug related events | 3 Event |
| VIS649 Cohort 3 | Overall Summary of Treatment Emergent Adverse Events | Moderate severity | 2 Event |
| VIS649 Cohort 3 | Overall Summary of Treatment Emergent Adverse Events | Adverse Events | 7 Event |
| VIS649 Cohort 3 | Overall Summary of Treatment Emergent Adverse Events | Mild severity | 1 Event |
| VIS649 Cohort 3 | Overall Summary of Treatment Emergent Adverse Events | Severe severity | 0 Event |
| VIS649 Cohort 3 | Overall Summary of Treatment Emergent Adverse Events | Serious Adverse Events | 0 Event |
| VIS649 Cohort 4 | Overall Summary of Treatment Emergent Adverse Events | Drug related events | 1 Event |
| VIS649 Cohort 4 | Overall Summary of Treatment Emergent Adverse Events | Serious Adverse Events | 0 Event |
| VIS649 Cohort 4 | Overall Summary of Treatment Emergent Adverse Events | Adverse Events | 7 Event |
| VIS649 Cohort 4 | Overall Summary of Treatment Emergent Adverse Events | Severe severity | 0 Event |
| VIS649 Cohort 4 | Overall Summary of Treatment Emergent Adverse Events | Mild severity | 3 Event |
| VIS649 Cohort 4 | Overall Summary of Treatment Emergent Adverse Events | Moderate severity | 0 Event |
| Placebo Cohort 5 + Vaccine | Overall Summary of Treatment Emergent Adverse Events | Adverse Events | 6 Event |
| Placebo Cohort 5 + Vaccine | Overall Summary of Treatment Emergent Adverse Events | Serious Adverse Events | 0 Event |
| Placebo Cohort 5 + Vaccine | Overall Summary of Treatment Emergent Adverse Events | Moderate severity | 0 Event |
| Placebo Cohort 5 + Vaccine | Overall Summary of Treatment Emergent Adverse Events | Severe severity | 0 Event |
| Placebo Cohort 5 + Vaccine | Overall Summary of Treatment Emergent Adverse Events | Drug related events | 1 Event |
| Placebo Cohort 5 + Vaccine | Overall Summary of Treatment Emergent Adverse Events | Mild severity | 3 Event |
| VIS649 Cohort 5 + Vaccine | Overall Summary of Treatment Emergent Adverse Events | Mild severity | 4 Event |
| VIS649 Cohort 5 + Vaccine | Overall Summary of Treatment Emergent Adverse Events | Drug related events | 0 Event |
| VIS649 Cohort 5 + Vaccine | Overall Summary of Treatment Emergent Adverse Events | Adverse Events | 4 Event |
| VIS649 Cohort 5 + Vaccine | Overall Summary of Treatment Emergent Adverse Events | Moderate severity | 0 Event |
| VIS649 Cohort 5 + Vaccine | Overall Summary of Treatment Emergent Adverse Events | Severe severity | 0 Event |
| VIS649 Cohort 5 + Vaccine | Overall Summary of Treatment Emergent Adverse Events | Serious Adverse Events | 0 Event |
Secondary
CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose.
The clearance rate (CL) of VIS649 using the exposure calculated to infinity of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants.
Time frame: Day 1 to day 112
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. | 31.46 mL/h | Standard Deviation 4.544 |
| VIS649 Cohort 1 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. | 11.70 mL/h | Standard Deviation 2.522 |
| VIS649 Cohort 2 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. | 6.125 mL/h | Standard Deviation 2.263 |
| VIS649 Cohort 3 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. | 4.508 mL/h | Standard Deviation 1.375 |
| VIS649 Cohort 4 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. | 8.724 mL/h | Standard Deviation 4.137 |
Secondary
CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. All Participants by Anti-VIS649 Antibody Status.
The clearance rate (CL) of VIS649 using the exposure calculated to infinity of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants by anti-VIS649 antibody status (positive or negative)..
Time frame: 112 days
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. All Participants by Anti-VIS649 Antibody Status. | CL--ADA negative participants | 31.460 mL/h | Standard Deviation 4.544 |
| VIS649 Cohort 1 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. All Participants by Anti-VIS649 Antibody Status. | CL--ADA positive participants | 13.750 mL/h | Standard Deviation 3.153 |
| VIS649 Cohort 1 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. All Participants by Anti-VIS649 Antibody Status. | CL--ADA negative participants | 10.870 mL/h | Standard Deviation 2.023 |
| VIS649 Cohort 2 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. All Participants by Anti-VIS649 Antibody Status. | CL--ADA positive participants | 5.097 mL/h | Standard Deviation 2.89 |
| VIS649 Cohort 2 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. All Participants by Anti-VIS649 Antibody Status. | CL--ADA negative participants | 6.536 mL/h | Standard Deviation 2.203 |
| VIS649 Cohort 3 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. All Participants by Anti-VIS649 Antibody Status. | CL--ADA negative participants | 4.019 mL/h | Standard Deviation 1.5 |
| VIS649 Cohort 3 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. All Participants by Anti-VIS649 Antibody Status. | CL--ADA positive participants | 4.875 mL/h | Standard Deviation 1.364 |
| VIS649 Cohort 4 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. All Participants by Anti-VIS649 Antibody Status. | CL--ADA positive participants | 7.445 mL/h | Standard Deviation 2.324 |
| VIS649 Cohort 4 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. All Participants by Anti-VIS649 Antibody Status. | CL--ADA negative participants | 9.272 mL/h | Standard Deviation 4.765 |
Secondary
CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. Japanese Participants
The clearance rate (CL) of VIS649 using the exposure calculated to infinity of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods.
Time frame: Day 1 to day 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) of Japanese ethnicity.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. Japanese Participants | 28.58 mL/h | Standard Deviation 1.794 |
| VIS649 Cohort 1 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. Japanese Participants | 12.26 mL/h | Standard Deviation 0.7651 |
| VIS649 Cohort 2 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. Japanese Participants | 4.385 mL/h | Standard Deviation 1.242 |
| VIS649 Cohort 3 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. Japanese Participants | 3.618 mL/h | Standard Deviation 1.442 |
Secondary
CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. Non-Japanese Participants
The clearance rate (CL) of VIS649 using the exposure calculated to infinity of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods.
Time frame: Day 1 to day 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) of non-Japanese ethnicity.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. Non-Japanese Participants | 33.63 mL/h | Standard Deviation 4.959 |
| VIS649 Cohort 1 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. Non-Japanese Participants | 11.27 mL/h | Standard Deviation 3.431 |
| VIS649 Cohort 2 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. Non-Japanese Participants | 7.430 mL/h | Standard Deviation 1.978 |
| VIS649 Cohort 3 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. Non-Japanese Participants | 5.175 mL/h | Standard Deviation 1.004 |
| VIS649 Cohort 4 | CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose. Non-Japanese Participants | 8.724 mL/h | Standard Deviation 4.137 |
Secondary
Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants
The maximum serum concentration (Cmax) of VIS649 determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants
Time frame: 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants | 12.600 μg/mL | Standard Deviation 2.222 |
| VIS649 Cohort 1 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants | 48.600 μg/mL | Standard Deviation 11.66 |
| VIS649 Cohort 2 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants | 135.900 μg/mL | Standard Deviation 20.38 |
| VIS649 Cohort 3 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants | 282.600 μg/mL | Standard Deviation 48.44 |
| VIS649 Cohort 4 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants | 130.700 μg/mL | Standard Deviation 20.15 |
Secondary
Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status
The maximum serum concentration (Cmax) of VIS649 determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants by anti-VIS649 status (positive or negative).
Time frame: 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Negative | 12.600 μg/mL | Standard Deviation 2.222 |
| VIS649 Cohort 1 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Positive | 48.450 μg/mL | Standard Deviation 15.34 |
| VIS649 Cohort 1 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Negative | 48.660 μg/mL | Standard Deviation 12.04 |
| VIS649 Cohort 2 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Positive | 140.500 μg/mL | Standard Deviation 13.44 |
| VIS649 Cohort 2 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Negative | 134.100 μg/mL | Standard Deviation 23.73 |
| VIS649 Cohort 3 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Negative | 259.000 μg/mL | Standard Deviation 65.11 |
| VIS649 Cohort 3 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Positive | 300.300 μg/mL | Standard Deviation 29.9 |
| VIS649 Cohort 4 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Positive | 117.700 μg/mL | Standard Deviation 21.14 |
| VIS649 Cohort 4 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Negative | 136.300 μg/mL | Standard Deviation 18.42 |
Secondary
Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Non-Japanese Participants
The maximum serum concentration (Cmax) of VIS649 determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods.
Time frame: 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) of non-Japanese ethnicity.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Non-Japanese Participants | 13.18 μg/mL | Standard Deviation 2.816 |
| VIS649 Cohort 1 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Non-Japanese Participants | 54.95 μg/mL | Standard Deviation 11.57 |
| VIS649 Cohort 2 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Non-Japanese Participants | 138.1 μg/mL | Standard Deviation 26.8 |
| VIS649 Cohort 3 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Non-Japanese Participants | 307.8 μg/mL | Standard Deviation 34.56 |
| VIS649 Cohort 4 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Non-Japanese Participants | 130.7 μg/mL | Standard Deviation 20.15 |
Secondary
Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Time Profile. Japanese Participants
The maximum serum concentration (Cmax) of VIS649 determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. Japanese participants
Time frame: 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) of Japanese ethnicity.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Time Profile. Japanese Participants | 11.83 μg/mL | Standard Deviation 1.172 |
| VIS649 Cohort 1 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Time Profile. Japanese Participants | 40.13 μg/mL | Standard Deviation 4.302 |
| VIS649 Cohort 2 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Time Profile. Japanese Participants | 133.0 μg/mL | Standard Deviation 12.12 |
| VIS649 Cohort 3 | Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Time Profile. Japanese Participants | 249.0 μg/mL | Standard Deviation 47.84 |
Secondary
Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4
The effect of VIS649 treatment on the population of circulating CD16 +CD56 (Natural killer) cells in serum for all participants in cohorts 1-4.
Time frame: From baseline to Week 24
Population: Pharmacodynamic population: the Safety Population subset with at least 1 pharmacodynamic parameter assessment post study drug dosing.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Baseline | 122.0 cells/mcl | Standard Deviation 156.14 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Week 4 | 142.5 cells/mcl | Standard Deviation 136.42 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Week 16 | 130.0 cells/mcl | Standard Deviation 30.41 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Week 20 | 204.0 cells/mcl | Standard Deviation 201.87 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Week 24 | 195.0 cells/mcl | Standard Deviation 173.776 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Week 16 | 150.0 cells/mcl | Standard Deviation 34.55 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Baseline | 136.0 cells/mcl | Standard Deviation 38.34 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Week 4 | 103.0 cells/mcl | Standard Deviation 46.6 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Week 16 | 226.0 cells/mcl | Standard Deviation 90.19 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Baseline | 174.0 cells/mcl | Standard Deviation 88.43 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Week 4 | 144.0 cells/mcl | Standard Deviation 46.13 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Week 24 | 135.0 cells/mcl | Standard Deviation 41.35 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Baseline | 107.0 cells/mcl | Standard Deviation 40.82 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Week 16 | 138.0 cells/mcl | Standard Deviation 49.69 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Week 4 | 143.0 cells/mcl | Standard Deviation 45.8 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Week 20 | 181.0 cells/mcl | Standard Deviation 58.45 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Baseline | 142.0 cells/mcl | Standard Deviation 48.32 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Week 4 | 181.0 cells/mcl | Standard Deviation 82.05 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Week 24 | 270.0 cells/mcl | Standard Deviation 142.83 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Week 16 | 153.0 cells/mcl | Standard Deviation 54.99 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4 | Week 20 | 189.0 cells/mcl | Standard Deviation 120.94 |
Secondary
Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4
The effect of VIS649 treatment on the population of circulating CD19 (B Cells) in serum for all participants in cohorts 1-4.
Time frame: From baseline to Week 24
Population: Pharmacodynamic population: the Safety Population subset with at least 1 pharmacodynamic parameter assessment post study drug dosing.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Baseline | 165 cells/uL | Standard Deviation 128.25 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Week 4 | 187.0 cells/uL | Standard Deviation 73.92 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Week 16 | 166.0 cells/uL | Standard Deviation 93.65 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Week 20 | 277.5 cells/uL | Standard Deviation 70.72 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Week 24 | 270.5 cells/uL | Standard Deviation 76.49 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Week 16 | 226.0 cells/uL | Standard Deviation 51.84 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Baseline | 193.0 cells/uL | Standard Deviation 23.72 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Week 4 | 206.0 cells/uL | Standard Deviation 34.69 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Week 16 | 209.0 cells/uL | Standard Deviation 98.99 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Baseline | 244.0 cells/uL | Standard Deviation 89.67 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Week 4 | 204.0 cells/uL | Standard Deviation 78.55 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Week 24 | 267.0 cells/uL | Standard Deviation 65.38 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Baseline | 268.0 cells/uL | Standard Deviation 79.96 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Week 16 | 359.0 cells/uL | Standard Deviation 113.22 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Week 4 | 294.0 cells/uL | Standard Deviation 129.97 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Week 20 | 320.0 cells/uL | Standard Deviation 146.34 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Baseline | 179.0 cells/uL | Standard Deviation 49.44 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Week 4 | 202.0 cells/uL | Standard Deviation 67.12 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Week 24 | 239.0 cells/uL | Standard Deviation 76.41 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Week 16 | 167.0 cells/uL | Standard Deviation 55.86 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4 | Week 20 | 190.0 cells/uL | Standard Deviation 72.04 |
Secondary
Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4
The effect of VIS649 treatment on the population of circulating CD3 T cells in serum for all participants in cohorts 1-4.
Time frame: From baseline to Week 24
Population: Pharmacodynamic population: the Safety Population subset with at least 1 pharmacodynamic parameter assessment post study drug dosing.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Baseline | 1147.5 cells/uL | Standard Deviation 313.07 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Week 4 | 1074.0 cells/uL | Standard Deviation 186.09 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Week 16 | 1025.0 cells/uL | Standard Deviation 300.38 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Week 20 | 1565.0 cells/uL | Standard Deviation 340.67 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Week 24 | 1644.5 cells/uL | Standard Deviation 299.56 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Week 16 | 1085.0 cells/uL | Standard Deviation 220.178 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Baseline | 1118.0 cells/uL | Standard Deviation 284.46 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Week 4 | 993.0 cells/uL | Standard Deviation 292.84 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Week 16 | 1082.0 cells/uL | Standard Deviation 140.94 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Baseline | 1218.0 cells/uL | Standard Deviation 200.2 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Week 4 | 1110.0 cells/uL | Standard Deviation 358.19 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Week 24 | 868.0 cells/uL | Standard Deviation 207.34 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Baseline | 985.0 cells/uL | Standard Deviation 365.33 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Week 16 | 1208.0 cells/uL | Standard Deviation 437.35 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Week 4 | 1018.0 cells/uL | Standard Deviation 407.5 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Week 20 | 970.0 cells/uL | Standard Deviation 387.46 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Baseline | 991.0 cells/uL | Standard Deviation 318.12 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Week 4 | 1226.0 cells/uL | Standard Deviation 433.57 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Week 24 | 1259.0 cells/uL | Standard Deviation 722.5 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Week 16 | 1270.0 cells/uL | Standard Deviation 367.31 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4 | Week 20 | 1139.0 cells/uL | Standard Deviation 558.77 |
Secondary
Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4
The effect of VIS649 treatment on the population of circulating CD4 T cells in serum for all participants in cohorts 1-4.
Time frame: From baseline to Week 24
Population: Pharmacodynamic population: the Safety Population subset with at least 1 pharmacodynamic parameter assessment post study drug dosing.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Baseline | 679.0 cells/uL | Standard Deviation 178 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Week 4 | 601.5 cells/uL | Standard Deviation 91.92 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Week 16 | 608.0 cells/uL | Standard Deviation 153.29 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Week 20 | 895.0 cells/uL | Standard Deviation 279.84 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Week 24 | 917.0 cells/uL | Standard Deviation 245.42 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Week 16 | 649.0 cells/uL | Standard Deviation 198.87 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Baseline | 592.0 cells/uL | Standard Deviation 156.93 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Week 4 | 631.0 cells/uL | Standard Deviation 182.52 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Week 16 | 718 cells/uL | Standard Deviation 127.74 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Baseline | 755.0 cells/uL | Standard Deviation 145.8 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Week 4 | 733.0 cells/uL | Standard Deviation 194.08 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Week 24 | 499.0 cells/uL | Standard Deviation 196.44 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Baseline | 553.0 cells/uL | Standard Deviation 288.67 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Week 16 | 606.0 cells/uL | Standard Deviation 347.79 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Week 4 | 592.0 cells/uL | Standard Deviation 337.55 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Week 20 | 630.0 cells/uL | Standard Deviation 300.58 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Baseline | 698.0 cells/uL | Standard Deviation 166.09 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Week 4 | 813.0 cells/uL | Standard Deviation 233.06 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Week 24 | 992.0 cells/uL | Standard Deviation 374.77 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Week 16 | 799.0 cells/uL | Standard Deviation 208.09 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4 | Week 20 | 738.0 cells/uL | Standard Deviation 255.19 |
Secondary
Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4
The effect of VIS649 treatment on the population of circulating CD8 T cells in serum for all participants in cohorts 1-4.
Time frame: From baseline to Week 24
Population: Pharmacodynamic population: the Safety Population subset with at least 1 pharmacodynamic parameter assessment post study drug dosing.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Baseline | 483.5 cells/uL | Standard Deviation 145.06 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Week 4 | 424.0 cells/uL | Standard Deviation 112.24 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Week 16 | 373.0 cells/uL | Standard Deviation 166.71 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Week 20 | 623.0 cells/uL | Standard Deviation 110.15 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Week 24 | 702.0 cells/uL | Standard Deviation 86.56 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Week 16 | 471.0 cells/uL | Standard Deviation 66.2 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Baseline | 442.0 cells/uL | Standard Deviation 165.29 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Week 4 | 338.0 cells/uL | Standard Deviation 135.81 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Week 16 | 349.0 cells/uL | Standard Deviation 66.96 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Baseline | 356.0 cells/uL | Standard Deviation 103.21 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Week 4 | 373.0 cells/uL | Standard Deviation 152.41 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Week 24 | 322.0 cells/uL | Standard Deviation 66.27 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Baseline | 373.0 cells/uL | Standard Deviation 108.08 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Week 16 | 391.0 cells/uL | Standard Deviation 137.52 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Week 4 | 370.0 cells/uL | Standard Deviation 129.55 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Week 20 | 362.0 cells/uL | Standard Deviation 145.02 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Baseline | 327 cells/uL | Standard Deviation 199.67 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Week 4 | 397.0 cells/uL | Standard Deviation 246.05 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Week 24 | 342.0 cells/uL | Standard Deviation 443.94 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Week 16 | 461.0 cells/uL | Standard Deviation 210.56 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4 | Week 20 | 416.0 cells/uL | Standard Deviation 359.67 |
Secondary
Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants
The effect of VIS649 treatment on total IgA levels in serum, weekly observations from Baseline to Week 24
Time frame: From baseline to Week 24
Population: Pharmacodynamic population: the Safety Population subset with at least 1 pharmacodynamic parameter assessment post study drug dosing.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 4 | 227.0 mg/dL | Standard Deviation 76.14 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 5 | 208.5 mg/dL | Standard Deviation 71.81 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 16 | 220.0 mg/dL | Standard Deviation 70.88 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 1 | 225.0 mg/dL | Standard Deviation 68.74 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 14 | 232.0 mg/dL | Standard Deviation 69.85 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Baseline | 217.0 mg/dL | Standard Deviation 70.44 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 2 | 222.5 mg/dL | Standard Deviation 74.97 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 24 | 239.0 mg/dL | Standard Deviation 94.36 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 12 | 227.5 mg/dL | Standard Deviation 74.44 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 10 | 215.5 mg/dL | Standard Deviation 67.79 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 3 | 217.0 mg/dL | Standard Deviation 73.17 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 20 | 243.5 mg/dL | Standard Deviation 90.16 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 8 | 217.0 mg/dL | Standard Deviation 68.26 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 7 | 229.0 mg/dL | Standard Deviation 68.86 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 6 | 217.5 mg/dL | Standard Deviation 71.98 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 4 | 169.0 mg/dL | Standard Deviation 75.99 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 16 | 179.0 mg/dL | Standard Deviation 69.35 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 8 | 159.5 mg/dL | Standard Deviation 74.21 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 5 | 164.0 mg/dL | Standard Deviation 64.44 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 2 | 151.0 mg/dL | Standard Deviation 60.23 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 6 | 167.0 mg/dL | Standard Deviation 67.82 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 3 | 147.0 mg/dL | Standard Deviation 54.07 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 1 | 165.0 mg/dL | Standard Deviation 64.1 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Baseline | 202.0 mg/dL | Standard Deviation 71.69 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 14 | 182.0 mg/dL | Standard Deviation 70.26 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 10 | 161.0 mg/dL | Standard Deviation 59.74 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 7 | 152.5 mg/dL | Standard Deviation 71.68 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 12 | 169.0 mg/dL | Standard Deviation 65.26 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 12 | 171.0 mg/dL | Standard Deviation 59.46 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Baseline | 213.0 mg/dL | Standard Deviation 82.89 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 1 | 223.0 mg/dL | Standard Deviation 64.03 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 2 | 168.0 mg/dL | Standard Deviation 52.76 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 3 | 158.0 mg/dL | Standard Deviation 49.15 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 4 | 134.0 mg/dL | Standard Deviation 48.87 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 5 | 133.0 mg/dL | Standard Deviation 43.46 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 6 | 140.0 mg/dL | Standard Deviation 51.43 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 7 | 148.0 mg/dL | Standard Deviation 53.76 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 8 | 148.5 mg/dL | Standard Deviation 59.02 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 10 | 171.0 mg/dL | Standard Deviation 60.8 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 14 | 164.0 mg/dL | Standard Deviation 63.82 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 16 | 165.0 mg/dL | Standard Deviation 89.38 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 14 | 195.5 mg/dL | Standard Deviation 105.85 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 8 | 109.0 mg/dL | Standard Deviation 68.4 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 4 | 152.0 mg/dL | Standard Deviation 87.08 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 5 | 142.0 mg/dL | Standard Deviation 87.7 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 16 | 158.0 mg/dL | Standard Deviation 116.54 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 20 | 172.0 mg/dL | Standard Deviation 117.3 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 7 | 113.0 mg/dL | Standard Deviation 74.53 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Baseline | 233.0 mg/dL | Standard Deviation 136.3 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 10 | 123.0 mg/dL | Standard Deviation 89.55 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 1 | 209.0 mg/dL | Standard Deviation 120.23 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 6 | 134.0 mg/dL | Standard Deviation 76.69 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 3 | 163.0 mg/dL | Standard Deviation 103.95 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 2 | 187.0 mg/dL | Standard Deviation 111.5 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 24 | 164.0 mg/dL | Standard Deviation 123.92 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 12 | 179.0 mg/dL | Standard Deviation 107.2 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 6 | 116.0 mg/dL | Standard Deviation 66.61 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 12 | 87.0 mg/dL | Standard Deviation 59.27 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 1 | 214.0 mg/dL | Standard Deviation 100.42 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 4 | 146.0 mg/dL | Standard Deviation 73.05 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 3 | 155.0 mg/dL | Standard Deviation 74.91 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 7 | 110.5 mg/dL | Standard Deviation 68.99 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 16 | 124.0 mg/dL | Standard Deviation 71.96 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 20 | 153.0 mg/dL | Standard Deviation 67.43 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 8 | 111.0 mg/dL | Standard Deviation 66.42 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 5 | 128.0 mg/dL | Standard Deviation 60.93 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Baseline | 243.0 mg/dL | Standard Deviation 96.48 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 2 | 174.0 mg/dL | Standard Deviation 82.09 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 10 | 105.0 mg/dL | Standard Deviation 61.87 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 24 | 153.5 mg/dL | Standard Deviation 83.43 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 14 | 109.0 mg/dL | Standard Deviation 56.66 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 6 | 207.0 mg/dL | Standard Deviation 90.44 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 3 | 193.0 mg/dL | Standard Deviation 84.93 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 8 | 210.0 mg/dL | Standard Deviation 92.31 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 2 | 205.0 mg/dL | Standard Deviation 83.7 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 10 | 207.0 mg/dL | Standard Deviation 83.97 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 1 | 198.0 mg/dL | Standard Deviation 84.45 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 12 | 192.0 mg/dL | Standard Deviation 85.87 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Baseline | 202.0 mg/dL | Standard Deviation 77 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 16 | 192.0 mg/dL | Standard Deviation 85.98 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 4 | 197.0 mg/dL | Standard Deviation 81.96 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 5 | 194.0 mg/dL | Standard Deviation 87.73 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 10 | 127.0 mg/dL | Standard Deviation 46.87 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 8 | 122.0 mg/dL | Standard Deviation 35.26 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 2 | 179.0 mg/dL | Standard Deviation 48.79 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 5 | 137.0 mg/dL | Standard Deviation 38.3 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 4 | 150.0 mg/dL | Standard Deviation 42.75 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 3 | 155.5 mg/dL | Standard Deviation 41.48 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 6 | 129.0 mg/dL | Standard Deviation 37 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 12 | 144.0 mg/dL | Standard Deviation 54.34 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 1 | 205.5 mg/dL | Standard Deviation 57.03 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Baseline | 222.5 mg/dL | Standard Deviation 65.16 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants | Week 16 | 169.0 mg/dL | Standard Deviation 52.57 |
Secondary
Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants
The effect of VIS649 treatment on total IgG levels in serum, weekly observations from baseline to Week 24
Time frame: From baseline to Week 24
Population: Pharmacodynamic population: the Safety Population subset with at least 1 pharmacodynamic parameter assessment post study drug dosing.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 4 | 1184.0 mg/dL | Standard Deviation 304.93 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 5 | 1143.5 mg/dL | Standard Deviation 237.34 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 16 | 1147.5 mg/dL | Standard Deviation 278.04 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 1 | 1152.0 mg/dL | Standard Deviation 323.58 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 14 | 1180.0 mg/dL | Standard Deviation 282.87 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Baseline | 1138.0 mg/dL | Standard Deviation 288.08 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 2 | 1150.5 mg/dL | Standard Deviation 280.89 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 24 | 1250.5 mg/dL | Standard Deviation 312.89 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 12 | 1215.0 mg/dL | Standard Deviation 282.42 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 10 | 1266.0 mg/dL | Standard Deviation 301.04 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 3 | 1174.0 mg/dL | Standard Deviation 293.55 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 20 | 1269.0 mg/dL | Standard Deviation 279.38 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 8 | 1199.5 mg/dL | Standard Deviation 311.2 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 7 | 1195.0 mg/dL | Standard Deviation 296 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 6 | 1185.5 mg/dL | Standard Deviation 295.65 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 4 | 1122.0 mg/dL | Standard Deviation 264.19 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 16 | 1072.0 mg/dL | Standard Deviation 242.2 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 8 | 1022.0 mg/dL | Standard Deviation 287.47 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 5 | 994.0 mg/dL | Standard Deviation 276.89 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 2 | 987.0 mg/dL | Standard Deviation 271.89 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 6 | 1105.0 mg/dL | Standard Deviation 285.27 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 3 | 946.0 mg/dL | Standard Deviation 242.33 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 1 | 1028.0 mg/dL | Standard Deviation 257.12 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Baseline | 1057 mg/dL | Standard Deviation 276.8 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 14 | 1038.0 mg/dL | Standard Deviation 278.83 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 10 | 1035.0 mg/dL | Standard Deviation 333.11 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 7 | 950.5 mg/dL | Standard Deviation 320.91 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 12 | 992.0 mg/dL | Standard Deviation 287.94 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 12 | 1036.0 mg/dL | Standard Deviation 238.29 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Baseline | 1243 mg/dL | Standard Deviation 293.55 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 1 | 1140.0 mg/dL | Standard Deviation 212.1 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 2 | 1120.0 mg/dL | Standard Deviation 220.63 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 3 | 1077.0 mg/dL | Standard Deviation 214.35 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 4 | 1038.0 mg/dL | Standard Deviation 218.35 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 5 | 965.0 mg/dL | Standard Deviation 193.19 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 6 | 990.0 mg/dL | Standard Deviation 216.58 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 7 | 1005.0 mg/dL | Standard Deviation 236.55 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 8 | 1022.5 mg/dL | Standard Deviation 220.65 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 10 | 985.0 mg/dL | Standard Deviation 234.14 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 14 | 930.0 mg/dL | Standard Deviation 268 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 16 | 934.0 mg/dL | Standard Deviation 356.27 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 14 | 1071.5 mg/dL | Standard Deviation 160.55 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 8 | 974.0 mg/dL | Standard Deviation 174.83 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 4 | 1053.0 mg/dL | Standard Deviation 196.39 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 5 | 1005.0 mg/dL | Standard Deviation 216.24 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 16 | 1104.0 mg/dL | Standard Deviation 233.23 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 20 | 1089.0 mg/dL | Standard Deviation 260.55 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 7 | 948.0 mg/dL | Standard Deviation 195.02 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Baseline | 1239.0 mg/dL | Standard Deviation 269.73 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 10 | 1006.0 mg/dL | Standard Deviation 223.84 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 1 | 1142.0 mg/dL | Standard Deviation 246.84 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 6 | 1001.0 mg/dL | Standard Deviation 212.64 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 3 | 1076 mg/dL | Standard Deviation 214.49 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 2 | 1108.0 mg/dL | Standard Deviation 196.16 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 24 | 1075.0 mg/dL | Standard Deviation 260.55 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 12 | 1027.0 mg/dL | Standard Deviation 168.63 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 6 | 850.0 mg/dL | Standard Deviation 191.4 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 12 | 718.0 mg/dL | Standard Deviation 185.8 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 1 | 1174.0 mg/dL | Standard Deviation 298.25 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 4 | 1034 mg/dL | Standard Deviation 221.08 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 3 | 999.0 mg/dL | Standard Deviation 212.58 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 7 | 929.0 mg/dL | Standard Deviation 184.67 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 16 | 876.0 mg/dL | Standard Deviation 220.38 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 20 | 1009.0 mg/dL | Standard Deviation 243.52 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 8 | 951.5 mg/dL | Standard Deviation 222.49 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 5 | 980.0 mg/dL | Standard Deviation 184.59 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Baseline | 1125.0 mg/dL | Standard Deviation 262.83 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 2 | 1038.0 mg/dL | Standard Deviation 240.46 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 10 | 841.0 mg/dL | Standard Deviation 196.81 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 24 | 917.5 mg/dL | Standard Deviation 91 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 14 | 862.0 mg/dL | Standard Deviation 180.07 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 6 | 1111.0 mg/dL | Standard Deviation 202.6 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 3 | 1063.0 mg/dL | Standard Deviation 202.43 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 8 | 1117.0 mg/dL | Standard Deviation 223.8 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 2 | 1117.0 mg/dL | Standard Deviation 201.08 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 10 | 1037.0 mg/dL | Standard Deviation 196.39 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 1 | 1098.0 mg/dL | Standard Deviation 225.06 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 12 | 1101.0 mg/dL | Standard Deviation 205.66 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Baseline | 1080.0 mg/dL | Standard Deviation 225.92 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 16 | 1198.0 mg/dL | Standard Deviation 156.1 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 4 | 1077.0 mg/dL | Standard Deviation 186.74 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 5 | 1094.0 mg/dL | Standard Deviation 180.03 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 10 | 845.0 mg/dL | Standard Deviation 211.71 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 8 | 953.0 mg/dL | Standard Deviation 192.19 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 2 | 1053.5 mg/dL | Standard Deviation 216.66 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 5 | 962.0 mg/dL | Standard Deviation 197.14 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 4 | 1050.0 mg/dL | Standard Deviation 204.29 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 3 | 966.5 mg/dL | Standard Deviation 235.63 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 6 | 971.0 mg/dL | Standard Deviation 194.19 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 12 | 970.0 mg/dL | Standard Deviation 256.28 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 1 | 1092.5 mg/dL | Standard Deviation 263.15 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Baseline | 1143.0 mg/dL | Standard Deviation 213.59 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants | Week 16 | 1049.0 mg/dL | Standard Deviation 261.94 |
Secondary
Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants
The effect of VIS649 treatment on total IgM levels in serum, weekly observations from Baseline to Week 24
Time frame: From baseline to Week 24
Population: Pharmacodynamic population: the Safety Population subset with at least 1 pharmacodynamic parameter assessment post study drug dosing.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 4 | 107.5 mg/dL | Standard Deviation 43.13 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 5 | 106.0 mg/dL | Standard Deviation 39.41 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 16 | 107.0 mg/dL | Standard Deviation 40.51 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 1 | 108.0 mg/dL | Standard Deviation 38.78 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 14 | 113.0 mg/dL | Standard Deviation 40.09 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Baseline | 105.0 mg/dL | Standard Deviation 43.75 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 2 | 109.5 mg/dL | Standard Deviation 42.39 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 24 | 89.0 mg/dL | Standard Deviation 33.56 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 12 | 113.0 mg/dL | Standard Deviation 41.39 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 10 | 104.5 mg/dL | Standard Deviation 40.87 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 3 | 105.0 mg/dL | Standard Deviation 39.49 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 20 | 80.0 mg/dL | Standard Deviation 42.54 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 8 | 110.5 mg/dL | Standard Deviation 40.73 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 7 | 109.5 mg/dL | Standard Deviation 44.41 |
| Pooled Placebo | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 6 | 106.5 mg/dL | Standard Deviation 42.1 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 4 | 84.0 mg/dL | Standard Deviation 40.45 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 16 | 127.0 mg/dL | Standard Deviation 40.51 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 8 | 89.5 mg/dL | Standard Deviation 37.91 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 5 | 83.0 mg/dL | Standard Deviation 34.54 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 2 | 91.0 mg/dL | Standard Deviation 39.04 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 6 | 92.0 mg/dL | Standard Deviation 37.21 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 3 | 85.0 mg/dL | Standard Deviation 34.49 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 1 | 117.0 mg/dL | Standard Deviation 39.91 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Baseline | 116.0 mg/dL | Standard Deviation 42.77 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 14 | 114.0 mg/dL | Standard Deviation 41.32 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 10 | 106.0 mg/dL | Standard Deviation 40.44 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 7 | 86.5 mg/dL | Standard Deviation 35.07 |
| VIS649 Cohort 1 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 12 | 106.0 mg/dL | Standard Deviation 37.89 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 12 | 54.0 mg/dL | Standard Deviation 36.41 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Baseline | 93.0 mg/dL | Standard Deviation 61.79 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 1 | 70.0 mg/dL | Standard Deviation 46.31 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 2 | 58.0 mg/dL | Standard Deviation 38.17 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 3 | 52.0 mg/dL | Standard Deviation 35.4 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 4 | 46.0 mg/dL | Standard Deviation 31.08 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 5 | 40.5 mg/dL | Standard Deviation 23.01 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 6 | 46.0 mg/dL | Standard Deviation 30.33 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 7 | 48.0 mg/dL | Standard Deviation 31.14 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 8 | 43.0 mg/dL | Standard Deviation 26.77 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 10 | 53.0 mg/dL | Standard Deviation 29.95 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 14 | 55.0 mg/dL | Standard Deviation 33.05 |
| VIS649 Cohort 2 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 16 | 60.0 mg/dL | Standard Deviation 30.7 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 14 | 82.5 mg/dL | Standard Deviation 30.31 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 8 | 46.0 mg/dL | Standard Deviation 23.8 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 4 | 58.0 mg/dL | Standard Deviation 34.95 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 5 | 49.0 mg/dL | Standard Deviation 32.13 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 16 | 78.0 mg/dL | Standard Deviation 39.52 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 20 | 90.0 mg/dL | Standard Deviation 38.11 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 7 | 43.0 mg/dL | Standard Deviation 23.88 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Baseline | 108.0 mg/dL | Standard Deviation 49.11 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 10 | 49.0 mg/dL | Standard Deviation 25.15 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 1 | 100.0 mg/dL | Standard Deviation 46.15 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 6 | 49 mg/dL | Standard Deviation 30.35 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 3 | 71.0 mg/dL | Standard Deviation 38.17 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 2 | 88.0 mg/dL | Standard Deviation 43.68 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 24 | 89.0 mg/dL | Standard Deviation 40.15 |
| VIS649 Cohort 3 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 12 | 73.5 mg/dL | Standard Deviation 26.46 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 6 | 57.0 mg/dL | Standard Deviation 21.07 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 12 | 35.0 mg/dL | Standard Deviation 20.3 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 1 | 128.0 mg/dL | Standard Deviation 28.8 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 4 | 75.0 mg/dL | Standard Deviation 25.32 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 3 | 80.0 mg/dL | Standard Deviation 26.13 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 7 | 51.5 mg/dL | Standard Deviation 18.5 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 16 | 55.0 mg/dL | Standard Deviation 24.08 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 20 | 69.0 mg/dL | Standard Deviation 23.84 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 8 | 46.0 mg/dL | Standard Deviation 19.31 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 5 | 60.0 mg/dL | Standard Deviation 19.85 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Baseline | 133.0 mg/dL | Standard Deviation 31.67 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 2 | 94.0 mg/dL | Standard Deviation 29.89 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 10 | 44.0 mg/dL | Standard Deviation 18.09 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 24 | 74.5 mg/dL | Standard Deviation 21.08 |
| VIS649 Cohort 4 | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 14 | 44.0 mg/dL | Standard Deviation 15.14 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 6 | 90 mg/dL | Standard Deviation 35.22 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 3 | 86.0 mg/dL | Standard Deviation 38.91 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 8 | 89.0 mg/dL | Standard Deviation 33.93 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 2 | 87.0 mg/dL | Standard Deviation 30.86 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 10 | 80.0 mg/dL | Standard Deviation 32.38 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 1 | 85.0 mg/dL | Standard Deviation 36.02 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 12 | 93.0 mg/dL | Standard Deviation 41.37 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Baseline | 85.0 mg/dL | Standard Deviation 35.75 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 16 | 93.0 mg/dL | Standard Deviation 31.11 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 4 | 81.0 mg/dL | Standard Deviation 35.91 |
| Placebo Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 5 | 84.0 mg/dL | Standard Deviation 35.5 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 10 | 49.0 mg/dL | Standard Deviation 19.53 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 8 | 42.0 mg/dL | Standard Deviation 11.07 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 2 | 87.0 mg/dL | Standard Deviation 25.15 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 5 | 54.0 mg/dL | Standard Deviation 15.41 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 4 | 68.0 mg/dL | Standard Deviation 20.35 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 3 | 73.5 mg/dL | Standard Deviation 24.02 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 6 | 48.0 mg/dL | Standard Deviation 13.3 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 12 | 63.0 mg/dL | Standard Deviation 25.09 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 1 | 102.5 mg/dL | Standard Deviation 31.82 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Baseline | 132.0 mg/dL | Standard Deviation 34.8 |
| VIS649 Cohort 5 + Vaccine | Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants | Week 16 | 87.0 mg/dL | Standard Deviation 30.55 |
Secondary
Summary of Anti -VIS649 Antibody (ADA) Titer by Treatment
Summary of Anti -VIS649 antibody (ADA) titer by treatment, all participants with ADA positive results
Time frame: Baseline to Day 112
Population: Safety Population
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| VIS649 Cohort 2 | Summary of Anti -VIS649 Antibody (ADA) Titer by Treatment | Week 16 | 32.0 titer | Standard Deviation 45.25 |
| VIS649 Cohort 2 | Summary of Anti -VIS649 Antibody (ADA) Titer by Treatment | Week 8 | 0.0 titer | — |
| VIS649 Cohort 3 | Summary of Anti -VIS649 Antibody (ADA) Titer by Treatment | Week 16 | 18.0 titer | Standard Deviation 19.8 |
| VIS649 Cohort 4 | Summary of Anti -VIS649 Antibody (ADA) Titer by Treatment | Week 16 | 6.0 titer | Standard Deviation 6.83 |
| VIS649 Cohort 5 + Vaccine | Summary of Anti -VIS649 Antibody (ADA) Titer by Treatment | Week 8 | 0.0 titer | — |
| VIS649 Cohort 5 + Vaccine | Summary of Anti -VIS649 Antibody (ADA) Titer by Treatment | Week 4 | 1.0 titer | — |
| VIS649 Cohort 5 + Vaccine | Summary of Anti -VIS649 Antibody (ADA) Titer by Treatment | Week 16 | 2.0 titer | Standard Deviation 2.83 |
Secondary
Summary of Anti -VIS649 Anti-drug Antibodies (ADA)
Summary of Anti -VIS649 anti-drug antibodies (ADA) by treatment group, all participants
Time frame: Baseline to Day 112
Population: Safety Population
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Pooled Placebo | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 4 | Negative | 8 Participants |
| Pooled Placebo | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Baseline | Positive | 0 Participants |
| Pooled Placebo | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Baseline | Negative | 8 Participants |
| Pooled Placebo | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 4 | Positive | 0 Participants |
| Pooled Placebo | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 8 | Negative | 8 Participants |
| Pooled Placebo | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 8 | Positive | 0 Participants |
| Pooled Placebo | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 16 | Negative | 8 Participants |
| Pooled Placebo | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 16 | Positive | 0 Participants |
| VIS649 Cohort 1 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Baseline | Positive | 0 Participants |
| VIS649 Cohort 1 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 16 | Positive | 0 Participants |
| VIS649 Cohort 1 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 4 | Negative | 7 Participants |
| VIS649 Cohort 1 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 4 | Positive | 0 Participants |
| VIS649 Cohort 1 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 8 | Negative | 6 Participants |
| VIS649 Cohort 1 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 8 | Positive | 0 Participants |
| VIS649 Cohort 1 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 16 | Negative | 7 Participants |
| VIS649 Cohort 1 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Baseline | Negative | 7 Participants |
| VIS649 Cohort 2 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 4 | Negative | 7 Participants |
| VIS649 Cohort 2 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 16 | Positive | 2 Participants |
| VIS649 Cohort 2 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 4 | Positive | 0 Participants |
| VIS649 Cohort 2 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 8 | Negative | 5 Participants |
| VIS649 Cohort 2 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 8 | Positive | 1 Participants |
| VIS649 Cohort 2 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 16 | Negative | 3 Participants |
| VIS649 Cohort 2 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Baseline | Positive | 0 Participants |
| VIS649 Cohort 2 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Baseline | Negative | 7 Participants |
| VIS649 Cohort 3 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 4 | Positive | 0 Participants |
| VIS649 Cohort 3 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 16 | Positive | 2 Participants |
| VIS649 Cohort 3 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 8 | Negative | 7 Participants |
| VIS649 Cohort 3 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 8 | Positive | 0 Participants |
| VIS649 Cohort 3 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 16 | Negative | 5 Participants |
| VIS649 Cohort 3 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 4 | Negative | 7 Participants |
| VIS649 Cohort 3 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Baseline | Negative | 7 Participants |
| VIS649 Cohort 3 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Baseline | Positive | 0 Participants |
| VIS649 Cohort 4 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 8 | Negative | 6 Participants |
| VIS649 Cohort 4 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 16 | Positive | 4 Participants |
| VIS649 Cohort 4 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 8 | Positive | 0 Participants |
| VIS649 Cohort 4 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 16 | Negative | 3 Participants |
| VIS649 Cohort 4 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 4 | Positive | 0 Participants |
| VIS649 Cohort 4 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Baseline | Negative | 7 Participants |
| VIS649 Cohort 4 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Baseline | Positive | 0 Participants |
| VIS649 Cohort 4 | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 4 | Negative | 7 Participants |
| Placebo Cohort 5 + Vaccine | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 8 | Positive | 0 Participants |
| Placebo Cohort 5 + Vaccine | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 16 | Positive | 0 Participants |
| Placebo Cohort 5 + Vaccine | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 16 | Negative | 5 Participants |
| Placebo Cohort 5 + Vaccine | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 8 | Negative | 5 Participants |
| Placebo Cohort 5 + Vaccine | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Baseline | Negative | 5 Participants |
| Placebo Cohort 5 + Vaccine | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Baseline | Positive | 0 Participants |
| Placebo Cohort 5 + Vaccine | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 4 | Negative | 5 Participants |
| Placebo Cohort 5 + Vaccine | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 4 | Positive | 0 Participants |
| VIS649 Cohort 5 + Vaccine | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 16 | Negative | 7 Participants |
| VIS649 Cohort 5 + Vaccine | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 8 | Positive | 1 Participants |
| VIS649 Cohort 5 + Vaccine | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 16 | Positive | 2 Participants |
| VIS649 Cohort 5 + Vaccine | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Baseline | Negative | 10 Participants |
| VIS649 Cohort 5 + Vaccine | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Baseline | Positive | 0 Participants |
| VIS649 Cohort 5 + Vaccine | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 4 | Negative | 8 Participants |
| VIS649 Cohort 5 + Vaccine | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 4 | Positive | 1 Participants |
| VIS649 Cohort 5 + Vaccine | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Week 8 | Negative | 8 Participants |
Secondary
T 1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants
The terminal elimination half life (t1/2) of VIS649 from the concentration-time profile as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods.
Time frame: 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | T 1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants | 60.72 hours | Standard Deviation 4.35 |
| VIS649 Cohort 1 | T 1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants | 175.20 hours | Standard Deviation 38.4 |
| VIS649 Cohort 2 | T 1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants | 230.90 hours | Standard Deviation 76.2 |
| VIS649 Cohort 3 | T 1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants | 670 hours | Standard Deviation 179.8 |
| VIS649 Cohort 4 | T 1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants | 342.10 hours | Standard Deviation 91.62 |
Secondary
T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status.
The terminal elimination half life (t1/2) of VIS649 from the concentration-time profile as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants by anti-VIS649 antibody status (negative/positive).
Time frame: 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status. | T1/2 ADA Negative participants | 60.720 hours | Standard Deviation 4.346 |
| VIS649 Cohort 1 | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status. | T1/2 ADA Positive participants | 131.900 hours | Standard Deviation 14.75 |
| VIS649 Cohort 1 | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status. | T1/2 ADA Negative participants | 192.600 hours | Standard Deviation 29.04 |
| VIS649 Cohort 2 | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status. | T1/2 ADA Positive participants | 246.600 hours | Standard Deviation 68.52 |
| VIS649 Cohort 2 | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status. | T1/2 ADA Negative participants | 224.600 hours | Standard Deviation 85.81 |
| VIS649 Cohort 3 | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status. | T1/2 ADA Negative participants | 738.4 hours | Standard Deviation 281.8 |
| VIS649 Cohort 3 | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status. | T1/2 ADA Positive participants | 618.8 hours | Standard Deviation 59.45 |
| VIS649 Cohort 4 | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status. | T1/2 ADA Positive participants | 358.200 hours | Standard Deviation 95.52 |
| VIS649 Cohort 4 | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status. | T1/2 ADA Negative participants | 335.300 hours | Standard Deviation 96.78 |
Secondary
T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. Japanese Participants
The terminal elimination half life (t1/2) of VIS649 from the concentration-time profile as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods.
Time frame: 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) Japanese participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. Japanese Participants | 59.24 hours | Standard Deviation 3.623 |
| VIS649 Cohort 1 | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. Japanese Participants | 158.8 hours | Standard Deviation 14.67 |
| VIS649 Cohort 2 | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. Japanese Participants | 189.8 hours | Standard Deviation 12.65 |
| VIS649 Cohort 3 | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. Japanese Participants | 778.4 hours | Standard Deviation 247.3 |
Secondary
T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. Non-Japanese Participants
The terminal elimination half life (t1/2) of VIS649 from the concentration-time profile as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. Non-Japanese participants.
Time frame: 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) non-Japanese participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. Non-Japanese Participants | 61.83 hours | Standard Deviation 5.017 |
| VIS649 Cohort 1 | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. Non-Japanese Participants | 187.6 hours | Standard Deviation 48.26 |
| VIS649 Cohort 2 | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. Non-Japanese Participants | 261.8 hours | Standard Deviation 92.45 |
| VIS649 Cohort 3 | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. Non-Japanese Participants | 588.8 hours | Standard Deviation 57.65 |
| VIS649 Cohort 4 | T1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. Non-Japanese Participants | 342.1 hours | Standard Deviation 91.62 |
Secondary
The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants
Summary of the pharmacokinetic profiles of VIS649 exposure in serum for all participants. AUC0-112 presents the area under the concentration time curve from pre-dose (time 0) to the concentration on day 112. AUC0-last presents the area under the concentration time curve from pre-dose (time 0) to the last quantifiable concentration. AUC0-inf presents the area under the concentration time curve from pre-dose (time 0) extrapolated to infinite time.
Time frame: 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) including all ethnicities.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants | AUC 0-112 days | 1118 h*μg/mL | Standard Deviation 209.4 |
| Pooled Placebo | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants | AUC 0-inf | 1118 h*μg/mL | Standard Deviation 209.5 |
| Pooled Placebo | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants | AUC 0-last | 885.2 h*μg/mL | Standard Deviation 146.2 |
| VIS649 Cohort 1 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants | AUC 0-last | 10510 h*μg/mL | Standard Deviation 2811 |
| VIS649 Cohort 1 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants | AUC 0-112 days | 11680 h*μg/mL | Standard Deviation 3402 |
| VIS649 Cohort 1 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants | AUC 0-inf | 11670 h*μg/mL | Standard Deviation 3403 |
| VIS649 Cohort 2 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants | AUC 0-last | 72760 h*μg/mL | Standard Deviation 19210 |
| VIS649 Cohort 2 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants | AUC 0-112 days | 74500 h*μg/mL | Standard Deviation 18570 |
| VIS649 Cohort 2 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants | AUC 0-inf | 74380 h*μg/mL | Standard Deviation 18620 |
| VIS649 Cohort 3 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants | AUC 0-112 days | 176300 h*μg/mL | Standard Deviation 26100 |
| VIS649 Cohort 3 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants | AUC 0-inf | 187400 h*μg/mL | Standard Deviation 35980 |
| VIS649 Cohort 3 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants | AUC 0-last | 148900 h*μg/mL | Standard Deviation 17460 |
| VIS649 Cohort 4 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants | AUC 0-last | 53630 h*μg/mL | Standard Deviation 18180 |
| VIS649 Cohort 4 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants | AUC 0-112 days | 57900 h*μg/mL | Standard Deviation 18390 |
| VIS649 Cohort 4 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants | AUC 0-inf | 57910 h*μg/mL | Standard Deviation 18390 |
Secondary
The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Japanese Participants
AUC0-112 presents the area under the concentration time curve from pre-dose (time 0) to the concentration on day 112. AUC0-last presents the area under the concentration time curve from pre-dose (time 0) to the last quantifiable concentration. AUC0-inf presents the area under the concentration time curve from pre-dose (time 0) extrapolated to infinite time.
Time frame: 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) Japanese participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Japanese Participants | AUC 0-112 days | 1039 h*μg/mL | Standard Deviation 56.05 |
| Pooled Placebo | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Japanese Participants | AUC 0-inf | 1039 h*μg/mL | Standard Deviation 56.01 |
| Pooled Placebo | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Japanese Participants | AUC 0-last | 820.6 h*μg/mL | Standard Deviation 25.48 |
| VIS649 Cohort 1 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Japanese Participants | AUC 0-112 days | 9405 h*μg/mL | Standard Deviation 434.5 |
| VIS649 Cohort 1 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Japanese Participants | AUC 0-inf | 9399 h*μg/mL | Standard Deviation 432.1 |
| VIS649 Cohort 1 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Japanese Participants | AUC 0-last | 8824 h*μg/mL | Standard Deviation 216.3 |
| VIS649 Cohort 2 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Japanese Participants | AUC 0-last | 85750 h*μg/mL | Standard Deviation 11220 |
| VIS649 Cohort 2 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Japanese Participants | AUC 0-112 days | 87210 h*μg/mL | Standard Deviation 11210 |
| VIS649 Cohort 2 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Japanese Participants | AUC 0-inf | 87170 h*μg/mL | Standard Deviation 11210 |
| VIS649 Cohort 3 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Japanese Participants | AUC 0-112 days | 185200 h*μg/mL | Standard Deviation 32550 |
| VIS649 Cohort 3 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Japanese Participants | AUC 0-inf | 203500 h*μg/mL | Standard Deviation 47430 |
| VIS649 Cohort 3 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Japanese Participants | AUC 0-last | 150300 h*μg/mL | Standard Deviation 21630 |
Secondary
The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants
Summary of the pharmacokinetic profiles of VIS649 exposure in serum for non-Japanese participants. AUC0-112 presents the area under the concentration time curve from pre-dose (time 0) to the concentration on day 112. AUC0-last presents the area under the concentration time curve from pre-dose (time 0) to the last quantifiable concentration. AUC0-inf presents the area under the concentration time curve from pre-dose (time 0) extrapolated to infinite time.
Time frame: 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) non-Japanese participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants | AUC 0-112 days | 1177 h*μg/mL | Standard Deviation 273.4 |
| Pooled Placebo | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants | AUC 0-inf | 1177 h*μg/mL | Standard Deviation 273.6 |
| Pooled Placebo | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants | AUC 0-last | 933.6 h*μg/mL | Standard Deviation 187.1 |
| VIS649 Cohort 1 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants | AUC 0-last | 11780 h*μg/mL | Standard Deviation 3283 |
| VIS649 Cohort 1 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants | AUC 0-112 days | 13380 h*μg/mL | Standard Deviation 3741 |
| VIS649 Cohort 1 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants | AUC 0-inf | 13380 h*μg/mL | Standard Deviation 3741 |
| VIS649 Cohort 2 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants | AUC 0-last | 63020 h*μg/mL | Standard Deviation 18950 |
| VIS649 Cohort 2 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants | AUC 0-112 days | 64960 h*μg/mL | Standard Deviation 17990 |
| VIS649 Cohort 2 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants | AUC 0-inf | 64790 h*μg/mL | Standard Deviation 17980 |
| VIS649 Cohort 3 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants | AUC 0-112 days | 169700 h*μg/mL | Standard Deviation 22790 |
| VIS649 Cohort 3 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants | AUC 0-inf | 175300 h*μg/mL | Standard Deviation 25200 |
| VIS649 Cohort 3 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants | AUC 0-last | 147900 h*μg/mL | Standard Deviation 17160 |
| VIS649 Cohort 4 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants | AUC 0-last | 53630 h*μg/mL | Standard Deviation 18180 |
| VIS649 Cohort 4 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants | AUC 0-112 days | 57900 h*μg/mL | Standard Deviation 18390 |
| VIS649 Cohort 4 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum. Non-Japanese Participants | AUC 0-inf | 57910 h*μg/mL | Standard Deviation 18390 |
Secondary
The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status.
Summary of the pharmacokinetic profiles of VIS649 exposure in serum for all participants based on their anti-VIS649 antibody status (negative/positive). AUC0-112 presents the area under the concentration time curve from pre-dose (time 0) to the concentration on day 112. AUC0-last presents the area under the concentration time curve from pre-dose (time 0) to the last quantifiable concentration. AUC0-inf presents the area under the concentration time curve from pre-dose (time 0) extrapolated to infinite time.
Time frame: 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) including all ethnicities.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-112 days--ADA Negative participants | 1118 h*μg/mL | Standard Deviation 209.4 |
| Pooled Placebo | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-inf--ADA negative participants | 1118 h*μg/mL | Standard Deviation 209.5 |
| Pooled Placebo | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-last--ADA negative participants | 885.2 h*μg/mL | Standard Deviation 146.2 |
| VIS649 Cohort 1 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-112 days--ADA Negative participants | 12270 h*μg/mL | Standard Deviation 3876 |
| VIS649 Cohort 1 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-last--ADA positive participants | 9922 h*μg/mL | Standard Deviation 1863 |
| VIS649 Cohort 1 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-inf--ADA positive participants | 10200 h*μg/mL | Standard Deviation 1806 |
| VIS649 Cohort 1 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-112 days--ADA Positive participants | 10200 h*μg/mL | Standard Deviation 1805 |
| VIS649 Cohort 1 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-last--ADA negative participants | 10750 h*μg/mL | Standard Deviation 3277 |
| VIS649 Cohort 1 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-inf--ADA negative participants | 12260 h*μg/mL | Standard Deviation 3878 |
| VIS649 Cohort 2 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-inf--ADA negative participants | 71340 h*μg/mL | Standard Deviation 19120 |
| VIS649 Cohort 2 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-inf--ADA positive participants | 81980 h*μg/mL | Standard Deviation 21350 |
| VIS649 Cohort 2 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-112 days--ADA Positive participants | 82120 h*μg/mL | Standard Deviation 21210 |
| VIS649 Cohort 2 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-112 days--ADA Negative participants | 71440 h*μg/mL | Standard Deviation 19090 |
| VIS649 Cohort 2 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-last--ADA negative participants | 69700 h*μg/mL | Standard Deviation 20050 |
| VIS649 Cohort 2 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-last--ADA positive participants | 80410 h*μg/mL | Standard Deviation 21040 |
| VIS649 Cohort 3 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-inf--ADA negative participants | 194300 h*μg/mL | Standard Deviation 49280 |
| VIS649 Cohort 3 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-last--ADA positive participants | 151800 h*μg/mL | Standard Deviation 19810 |
| VIS649 Cohort 3 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-last--ADA negative participants | 145100 h*μg/mL | Standard Deviation 16950 |
| VIS649 Cohort 3 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-112 days--ADA Positive participants | 175300 h*μg/mL | Standard Deviation 26540 |
| VIS649 Cohort 3 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-inf--ADA positive participants | 182100 h*μg/mL | Standard Deviation 29760 |
| VIS649 Cohort 3 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-112 days--ADA Negative participants | 177700 h*μg/mL | Standard Deviation 31330 |
| VIS649 Cohort 4 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-inf--ADA positive participants | 61320 h*μg/mL | Standard Deviation 23060 |
| VIS649 Cohort 4 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-112 days--ADA Negative participants | 56390 h*μg/mL | Standard Deviation 17870 |
| VIS649 Cohort 4 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-112 days--ADA Positive participants | 61450 h*μg/mL | Standard Deviation 23170 |
| VIS649 Cohort 4 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-last--ADA negative participants | 51550 h*μg/mL | Standard Deviation 17860 |
| VIS649 Cohort 4 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-last--ADA positive participants | 58500 h*μg/mL | Standard Deviation 21880 |
| VIS649 Cohort 4 | The Pharmacokinetic Exposure Profiles of VIS649 in Serum Samples, All Participants by Anti-VIS649 Antibody Status. | AUC 0-inf--ADA negative participants | 56450 h*μg/mL | Standard Deviation 17930 |
Secondary
Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participant
The time to the maximum serum concentration (tmax) of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants
Time frame: 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pooled Placebo | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participant | 1.136 hours |
| VIS649 Cohort 1 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participant | 3.045 hours |
| VIS649 Cohort 2 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participant | 3.038 hours |
| VIS649 Cohort 3 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participant | 1.148 hours |
| VIS649 Cohort 4 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participant | 3.053 hours |
Secondary
Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status
The time to the maximum serum concentration (tmax) of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants by anti-VIS649 status (positive or negative).
Time frame: 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Pooled Placebo | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Negative | 1.136 hours |
| VIS649 Cohort 1 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Negative | 1.434 hours |
| VIS649 Cohort 1 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Positive | 3.058 hours |
| VIS649 Cohort 2 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Negative | 3.038 hours |
| VIS649 Cohort 2 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Positive | 2.089 hours |
| VIS649 Cohort 3 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Positive | 1.142 hours |
| VIS649 Cohort 3 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Negative | 3.064 hours |
| VIS649 Cohort 4 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Negative | 3.049 hours |
| VIS649 Cohort 4 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status | Positive | 3.055 hours |
Secondary
Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Japanese Participants
The time to the maximum serum concentration (tmax) of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. Japanese participants.
Time frame: 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) of Japanese ethnicity.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pooled Placebo | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Japanese Participants | 1.136 hours |
| VIS649 Cohort 1 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Japanese Participants | 3.045 hours |
| VIS649 Cohort 2 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Japanese Participants | 3.049 hours |
| VIS649 Cohort 3 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Japanese Participants | 3.064 hours |
Secondary
Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Non-Japanese Participants
The time to the maximum serum concentration (tmax) of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods.
Time frame: 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) of non-Japanese ethnicity.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pooled Placebo | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Non-Japanese Participants | 1.170 hours |
| VIS649 Cohort 1 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Non-Japanese Participants | 2.253 hours |
| VIS649 Cohort 2 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Non-Japanese Participants | 2.159 hours |
| VIS649 Cohort 3 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Non-Japanese Participants | 1.142 hours |
| VIS649 Cohort 4 | Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Non-Japanese Participants | 3.053 hours |
Secondary
Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants
The volume of distribution of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants.
Time frame: Day 1 to day 112
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants | 2747 mL | Standard Deviation 351.6 |
| VIS649 Cohort 1 | Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants | 2854 mL | Standard Deviation 323.5 |
| VIS649 Cohort 2 | Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants | 2183 mL | Standard Deviation 1365 |
| VIS649 Cohort 3 | Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants | 4122 mL | Standard Deviation 780.4 |
| VIS649 Cohort 4 | Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants | 3911 mL | Standard Deviation 828.4 |
Secondary
Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status (Positive or Negative)
The calculated volume of distribution of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods. All participants by anti-VIS649 antibody status (positive or negative).
Time frame: 112 days
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pooled Placebo | Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status (Positive or Negative) | Vd--ADA negative | 2747 mL | Standard Deviation 351.6 |
| VIS649 Cohort 1 | Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status (Positive or Negative) | Vd--ADA negative | 2961 mL | Standard Deviation 287.2 |
| VIS649 Cohort 1 | Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status (Positive or Negative) | Vd--ADA positive | 2584 mL | Standard Deviation 307.5 |
| VIS649 Cohort 2 | Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status (Positive or Negative) | Vd--ADA positive | 1956 mL | Standard Deviation 1532 |
| VIS649 Cohort 2 | Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status (Positive or Negative) | Vd--ADA negative | 2274 mL | Standard Deviation 1474 |
| VIS649 Cohort 3 | Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status (Positive or Negative) | Vd--ADA negative | 3894 mL | Standard Deviation 548.8 |
| VIS649 Cohort 3 | Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status (Positive or Negative) | Vd--ADA positive | 4292 mL | Standard Deviation 962.6 |
| VIS649 Cohort 4 | Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status (Positive or Negative) | Vd--ADA negative | 4026 mL | Standard Deviation 983.8 |
| VIS649 Cohort 4 | Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status (Positive or Negative) | Vd--ADA positive | 3641 mL | Standard Deviation 171.1 |
Secondary
Vd: The Volume of Distribution of VIS649 in Serum Samples. Japanese Participants
The volume of distribution of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods.
Time frame: Day 1 to day 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) of Japanese ethnicity.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | Vd: The Volume of Distribution of VIS649 in Serum Samples. Japanese Participants | 2441 mL | Standard Deviation 197.9 |
| VIS649 Cohort 1 | Vd: The Volume of Distribution of VIS649 in Serum Samples. Japanese Participants | 2816 mL | Standard Deviation 390.3 |
| VIS649 Cohort 2 | Vd: The Volume of Distribution of VIS649 in Serum Samples. Japanese Participants | 1197 mL | Standard Deviation 344.5 |
| VIS649 Cohort 3 | Vd: The Volume of Distribution of VIS649 in Serum Samples. Japanese Participants | 3772 mL | Standard Deviation 674.7 |
Secondary
Vd: The Volume of Distribution of VIS649 in Serum Samples. Non-Japanese Participants
The volume of distribution of VIS649 as determined by an electrochemiluminescence (ECL) immunoassay and analyzed by standard non-compartmental pharmacokinetic methods.
Time frame: Day 1 to day 112.
Population: Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) of non-Japanese ethnicity.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pooled Placebo | Vd: The Volume of Distribution of VIS649 in Serum Samples. Non-Japanese Participants | 2976 mL | Standard Deviation 241 |
| VIS649 Cohort 1 | Vd: The Volume of Distribution of VIS649 in Serum Samples. Non-Japanese Participants | 2882 mL | Standard Deviation 324.3 |
| VIS649 Cohort 2 | Vd: The Volume of Distribution of VIS649 in Serum Samples. Non-Japanese Participants | 2923 mL | Standard Deviation 1395 |
| VIS649 Cohort 3 | Vd: The Volume of Distribution of VIS649 in Serum Samples. Non-Japanese Participants | 4384 mL | Standard Deviation 837 |
| VIS649 Cohort 4 | Vd: The Volume of Distribution of VIS649 in Serum Samples. Non-Japanese Participants | 3911 mL | Standard Deviation 828.4 |