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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.
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| VIS649 | Experimental | A single dose of VIS649 will be administered IV over approximately 1 hour on Day 1, at doses ranging from 0.5 mg/kg up to but not to exceed 20 mg/kg. No other doses will be administered during the study. |
|
| Placebo | Placebo Comparator | Single IV dose of placebo will be administered via IV over approximately 1 hour on Day 1. No other doses will be administered during the study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VIS649 | Biological | Single IV dose of study product on Day 1 of study |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Baseline to day 112 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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Inclusion Criteria:
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.
Male and female subjects between 18 to 55 years of age, inclusive, at the Screening Visit.
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).
For non-Japanese subjects: Subjects must be of non-Asian descent, as evidenced by verbal confirmation that all four grandparents are non-Asian.
The following applies to female subjects:
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.
Screening laboratory values must meet the following criteria:
Body mass index (BMI) between 18 and 32 kg/m2, inclusive, at the Screening Visit.
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.
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.
QTcF or QTcB < 450 msec at Screening (may be repeated once).
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Esther Yoon, MD | Parexel | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| California Clinical Trials Medical Group | Glendale | California | 91206 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35570983 | Derived | Mathur M, Barratt J, Suzuki Y, Engler F, Pasetti MF, Yarbrough J, Sloan S, Oldach D. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VIS649 (Sibeprenlimab), an APRIL-Neutralizing IgG2 Monoclonal Antibody, in Healthy Volunteers. Kidney Int Rep. 2022 Feb 8;7(5):993-1003. doi: 10.1016/j.ekir.2022.01.1073. eCollection 2022 May. |
| Label | URL |
|---|---|
| Otsuka Clinical Trial Website | View source |
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No notable events took place between participant enrollment and assignment.
Recruitment was done for a single clinical site.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pooled Placebo | Single IV dose of placebo will be administered via IV over approximately 1 hour on Day 1. |
| FG001 | VIS649 Cohort 1 | A single dose (0.5 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. |
| FG002 | VIS649 Cohort 2 | A single dose (2.0 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. |
| FG003 | VIS649 Cohort 3 | A single dose (6.0 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. |
| FG004 | VIS649 Cohort 4 | A single dose (12 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. |
| FG005 | Placebo Cohort 5 + Vaccine | Single dose of placebo followed by single dose of vaccine |
| FG006 | VIS649 Cohort 5 + Vaccine | Single dose of 6.0 mg/kg VIS649 followed by single dose of vaccine |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Pooled Placebo | Single IV dose of placebo will be administered via IV over approximately 1 hour on Day 1. |
| BG001 | VIS649 Cohort 1 | A single dose (0.5 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Safety Population | Posted | Number | Event | Baseline to day 112 |
|
From Day -1 to Day 112
Standard definitions of adverse and serious adverse event were used. Severity was either mild, moderate or severe as determined by the investigator using standard criteria in the protocol. All participants were monitored in the clinic for 24 hours post dose. Additional clinical visits occurred on days 3, 7, 14, 21, 28, 35, 42, 49, 56, 70, 84, 98, 112.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pooled Placebo | Single IV dose of placebo will be administered via IV over approximately 1 hour on Day 1. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea, Food poisoning, Constipation, or Vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Principal Investigator | Parexel International | (781) 487-9900 | info@parexel.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol: Protocol Amendment 2 | Mar 12, 2019 | Jan 3, 2025 | Prot_000.pdf |
| Prot | Yes | No | No | Study Protocol: Protocol Amendment 1 | Dec 20, 2018 | Jan 3, 2025 | Prot_001.pdf |
| Prot | Yes | No | No | Study Protocol: Final Protocol | Aug 20, 2018 | Jan 3, 2025 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 3, 2019 | Jan 3, 2025 | SAP_003.pdf |
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| ID | Term |
|---|---|
| D005922 | Glomerulonephritis, IGA |
| ID | Term |
|---|---|
| D005921 | Glomerulonephritis |
| D009393 | Nephritis |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
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phase 1, randomized, placebo-controlled, double-blind, single ascending dose study
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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.
| Placebo |
| Biological |
Singe IV dose of placebo administered via IV on Day 1 of study |
|
| 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 | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
| 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. | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
| 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. | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
| 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. | Day 1 to day 112 |
| 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. | Day 1 to day 112 |
| 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 | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
| 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. | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
| 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. | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
| 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. | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
| 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. | Day 1 to day 112. |
| 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. | Day 1 to day 112. |
| 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. | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
| 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. | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
| 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. | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
| 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. | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
| 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. | Day 1 to day 112. |
| 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. | Day 1 to day 112. |
| 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 | From baseline to Week 24 |
| 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 | From baseline to Week 24 |
| 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 | From baseline to Week 24 |
| 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. | From baseline to Week 24 |
| 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. | From baseline to Week 24 |
| 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. | From baseline to Week 24 |
| 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. | From baseline to Week 24 |
| 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. | From baseline to Week 24 |
| Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Summary of Anti -VIS649 anti-drug antibodies (ADA) by treatment group, all participants | Baseline to Day 112 |
| Summary of Anti -VIS649 Antibody (ADA) Titer by Treatment | Summary of Anti -VIS649 antibody (ADA) titer by treatment, all participants with ADA positive results | Baseline to Day 112 |
| 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). | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
| 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). | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
| 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. | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
| 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). | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
| 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).. | 112 days |
| 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). | 112 days |
| Otsuka Clinical Trial Transparency | View source |
| Withdrawal by Subject |
|
| BG002 | VIS649 Cohort 2 | A single dose (2.0 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. |
| BG003 | VIS649 Cohort 3 | A single dose (6.0 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. |
| BG004 | VIS649 Cohort 4 | A single dose (12 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. |
| BG005 | Placebo Cohort 5 + Vaccine | Single dose of placebo followed by single dose of vaccine |
| BG006 | VIS649 Cohort 5 + Vaccine | Single dose of 6.0 mg/kg VIS649 followed by single dose of vaccine |
| BG007 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Height (cm) | Mean | Standard Deviation | cm |
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| Weight (kg) | Mean | Standard Deviation | Kg |
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| Body Mass Index | Mean | Standard Deviation | kg/m2 |
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| VIS649 Cohort 2 |
A single dose (2.0 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. |
| OG003 | VIS649 Cohort 3 | A single dose (6.0 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. |
| OG004 | VIS649 Cohort 4 | A single dose (12 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. |
| OG005 | Placebo Cohort 5 + Vaccine | Single dose of placebo followed by single dose of vaccine |
| OG006 | VIS649 Cohort 5 + Vaccine | Single dose of 6.0 mg/kg VIS649 followed by single dose of vaccine |
|
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| 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 | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration). | Posted | Mean | Standard Deviation | μg/mL | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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| 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 | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration). | Posted | Median | Full Range | hours | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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| 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. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) including all ethnicities. | Posted | Mean | Standard Deviation | h*μg/mL | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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| 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. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration). | Posted | Mean | Standard Deviation | hours | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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| 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. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration). | Posted | Mean | Standard Deviation | mL/h | Day 1 to day 112 |
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| 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. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration). | Posted | Mean | Standard Deviation | mL | Day 1 to day 112 |
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| 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 | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) of Japanese ethnicity. | Posted | Mean | Standard Deviation | μg/mL | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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| 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. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) of Japanese ethnicity. | Posted | Median | Full Range | hours | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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| 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. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) Japanese participants. | Posted | Mean | Standard Deviation | h*μg/mL | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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| 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. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) Japanese participants. | Posted | Mean | Standard Deviation | hours | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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| 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. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) of Japanese ethnicity. | Posted | Mean | Standard Deviation | mL/h | Day 1 to day 112. |
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| 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. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) of Japanese ethnicity. | Posted | Mean | Standard Deviation | mL | Day 1 to day 112. |
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| 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. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) of non-Japanese ethnicity. | Posted | Mean | Standard Deviation | μg/mL | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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| 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. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) of non-Japanese ethnicity. | Posted | Median | Full Range | hours | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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| 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. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) non-Japanese participants. | Posted | Mean | Standard Deviation | h*μg/mL | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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| 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. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) non-Japanese participants. | Posted | Mean | Standard Deviation | hours | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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| 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. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) of non-Japanese ethnicity. | Posted | Mean | Standard Deviation | mL/h | Day 1 to day 112. |
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| 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. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) of non-Japanese ethnicity. | Posted | Mean | Standard Deviation | mL | Day 1 to day 112. |
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| 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 | Pharmacodynamic population: the Safety Population subset with at least 1 pharmacodynamic parameter assessment post study drug dosing. | Posted | Median | Standard Deviation | mg/dL | From baseline to Week 24 |
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| 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 | Pharmacodynamic population: the Safety Population subset with at least 1 pharmacodynamic parameter assessment post study drug dosing. | Posted | Median | Standard Deviation | mg/dL | From baseline to Week 24 |
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| 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 | Pharmacodynamic population: the Safety Population subset with at least 1 pharmacodynamic parameter assessment post study drug dosing. | Posted | Median | Standard Deviation | mg/dL | From baseline to Week 24 |
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| 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. | Pharmacodynamic population: the Safety Population subset with at least 1 pharmacodynamic parameter assessment post study drug dosing. | Posted | Median | Standard Deviation | cells/mcl | From baseline to Week 24 |
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| 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. | Pharmacodynamic population: the Safety Population subset with at least 1 pharmacodynamic parameter assessment post study drug dosing. | Posted | Median | Standard Deviation | cells/uL | From baseline to Week 24 |
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| 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. | Pharmacodynamic population: the Safety Population subset with at least 1 pharmacodynamic parameter assessment post study drug dosing. | Posted | Median | Standard Deviation | cells/uL | From baseline to Week 24 |
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| 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. | Pharmacodynamic population: the Safety Population subset with at least 1 pharmacodynamic parameter assessment post study drug dosing. | Posted | Median | Standard Deviation | cells/uL | From baseline to Week 24 |
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| 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. | Pharmacodynamic population: the Safety Population subset with at least 1 pharmacodynamic parameter assessment post study drug dosing. | Posted | Median | Standard Deviation | cells/uL | From baseline to Week 24 |
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| Secondary | Summary of Anti -VIS649 Anti-drug Antibodies (ADA) | Summary of Anti -VIS649 anti-drug antibodies (ADA) by treatment group, all participants | Safety Population | Posted | Count of Participants | Participants | Baseline to Day 112 |
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| 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 | Safety Population | Posted | Median | Standard Deviation | titer | Baseline to Day 112 |
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| 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). | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration). | Posted | Mean | Standard Deviation | μg/mL | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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| 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). | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration). | Posted | Median | Full Range | hours | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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| 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. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration) including all ethnicities. | Posted | Mean | Standard Deviation | h*μg/mL | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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| 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). | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration). | Posted | Mean | Standard Deviation | hours | 0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112. |
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| 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).. | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration). | Posted | Mean | Standard Deviation | mL/h | 112 days |
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| 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). | Pharmacokinetic Population (all randomized participants with at least 1 quantifiable VIS649 concentration). | Posted | Mean | Standard Deviation | mL | 112 days |
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| 0 |
| 8 |
| 0 |
| 8 |
| 4 |
| 8 |
| EG001 | VIS649 Cohort 1 | A single dose (0.5 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. | 0 | 7 | 0 | 7 | 2 | 7 |
| EG002 | VIS649 Cohort 2 | A single dose (2.0 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. | 0 | 7 | 0 | 7 | 3 | 7 |
| EG003 | VIS649 Cohort 3 | A single dose (6.0 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. | 0 | 7 | 0 | 7 | 3 | 7 |
| EG004 | VIS649 Cohort 4 | A single dose (12 mg/kg) of VIS649 administered IV over approximately 1 hour on Day 1. | 0 | 7 | 0 | 7 | 3 | 7 |
| EG005 | Placebo Cohort 5 + Vaccine | Single dose of placebo followed by single dose of vaccine | 0 | 5 | 0 | 5 | 3 | 5 |
| EG006 | VIS649 Cohort 5 + Vaccine | Single dose of 6.0 mg/kg VIS649 followed by single dose of vaccine | 0 | 10 | 0 | 10 | 4 | 10 |
| General disorders and administration site conditions | General disorders | Systematic Assessment |
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| Infections and infestations | Infections and infestations | Systematic Assessment |
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| Dizziness, Headache, Head discomfort, Migraine, Somnolence, Syncope, or Taste disorder | Nervous system disorders | Systematic Assessment |
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| Sunburn | Injury, poisoning and procedural complications | Systematic Assessment |
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| Back pain or Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Oropharyngeal pain or Sneezing | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Rash papular | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Blepharitis | Eye disorders | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | Systematic Assessment |
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| Menopausal symptoms | Reproductive system and breast disorders | Systematic Assessment |
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Not provided
Not provided
| D052776 |
| Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| AUC 0-last |
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| Positive |
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| Positive |
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| AUC 0-112 days--ADA Positive participants |
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| T1/2 ADA Positive participants |
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| CL--ADA positive participants |
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| Vd--ADA positive |
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| Positive |
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| Positive |
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| Positive |
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