First in Human Study to Assess Safety of VIS649 in Healthy Subjects
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|ClinicalTrials.gov Identifier: NCT03719443|
Recruitment Status : Completed
First Posted : October 25, 2018
Last Update Posted : March 6, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Immunoglobulin A Nephropathy IgAN - IgA Nephropathy IgA Nephropathy||Biological: VIS649 Biological: Placebo||Phase 1|
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).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||41 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||phase 1, randomized, placebo-controlled, double-blind, single ascending dose study|
|Masking:||Quadruple (Participant, Care Provider, 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.|
|Official Title:||A Phase 1, Randomized, Placebo-Controlled, Single Ascending Dose First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of VIS649 Administered Intravenously in Healthy Subjects|
|Actual Study Start Date :||October 9, 2018|
|Actual Primary Completion Date :||August 10, 2019|
|Actual Study Completion Date :||August 10, 2019|
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.
Single IV dose of study product on Day 1 of study
Placebo Comparator: Placebo
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.
Singe IV dose of placebo administered via IV on Day 1 of study
- Number of participants with treatment-emergent adverse events [ Time Frame: 112 days ]The proportion of subjects with AEs and serious adverse events (SAEs) following administration of VIS649. Safety will be assessed via AE severity per CTCAE v4.0
- Frequency of 12-lead ECG treatment emergent abnormalities [ Time Frame: 112 days ]QT interval change will be measured with Bazett (QTcB) or Fridericia (QTcF) heart rate correction formulas
- The levels of anti-drug antibodies [ Time Frame: 112 days ]Blood anti-drug antibodies (ADA) level assessments over time
- The PK profile of VIS649 in serum/blood samples [ Time Frame: 112 days ]characterize blood VIS649 concentration over time
- The effect of VIS649 on pharmacodynamic (PD) parameters [ Time Frame: 112 days ]Changes in serum immunoglobulin levels over time
- The effect of VIS649 on pharmacodynamic (PD) parameters [ Time Frame: 112 days ]Changes in plasma (or serum) APRIL levels
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03719443
|United States, California|
|California Clinical Trials Medical Group|
|Glendale, California, United States, 91206|
|Principal Investigator:||Esther Yoon, MD||Parexel|