Immunoglobulin A NephropathyPhase 1NCT03719443
First in Human Study to Assess Safety of VIS649 in Healthy Subjects
A Phase 1 study testing VIS649 in people with Immunoglobulin A Nephropathy and IgAN - IgA Nephropathy, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Immunoglobulin A Nephropathy, IgAN - IgA Nephropathy, IgA Nephropathy
- What is being tested?
- VIS649
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Oct 2018to 10 Aug 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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:
- Non-childbearing potential (surgically sterile [hysterectomy or bilateral tubal ligation]) for at least 6 months, or postmenopausal ≥ 1 year, or
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- 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.
- 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:
- 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)
- 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).
Who cannot join
- 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).
- Subject is judged by the Investigator or the Medical Monitor to be inappropriate for the study.
- 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.
- 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.
- 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.
- History of a previous severe allergic reaction with generalized urticaria; angioedema or anaphylaxis.
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- Blood pressure >160/100 mmHg or <90/50 mmHg (may be repeated once if abnormal), at the Screening visit and Day 1.
- Known hypoglobulinemia disorder (i.e., common variable immunodeficiency), X linked agammaglobulinemia, selective IgA deficiency, selective IgM deficiency).
- 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.
- 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).
- 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).
- 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.
- 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.
- 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).
- 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.
- Subjects with a positive urine drug (inclusive of marijuana) or alcohol Screening test result at Screening and Day -1.
- 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).
- Subjects with a known history of a positive Human Immunodeficiency Virus (HIV) or a positive test result at Screening.
- Subjects who have donated >500 mL or blood within 60 days prior to start of Screening.
- The subject has donated any plasma within 7 days prior to Baseline (Day -1).
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
California Clinical Trials Medical Group
Glendale, California, 91206
About this study
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
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.
Read the 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).
- Being tested
- VIS649, Placebo
- Keywords
- chronic glomerular disease, autoimmune glomerulonephritis
- Medical subject headings
- Glomerulonephritis, IGA
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VIS649Biological
Single IV dose of study product on Day 1 of study
PlaceboBiological
Singe IV dose of placebo administered via IV on Day 1 of study
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: VIS649 |
| 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. Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Baseline to day 112
Secondary outcomes (34)
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
Measured: 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 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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)..
Measured: 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).
Measured: 112 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2018
- Study start9 Oct 2018
- Primary completion10 Aug 2019
- Study completion10 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Immunoglobulin A NephropathyStudies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- phase 1, randomized, placebo-controlled, double-blind, single ascending dose study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Esther Yoon, MD, Principal investigator, Parexel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03719443
- Sponsor's protocol ID
- VIS649-101
- Status last verified
- Apr 2026
- First submitted
- 10 Oct 2018
- Last updated
- 1 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
McCafferty K, Barratt J, Suzuki Y, Liew A, Rizk DV, Chacko B, Kooienga L, Lafayette R, Wong MG, Pasetti MF, Shriver MC, Follman K, Moc Willeford C, Sahay M, Honig G, Andrews L, Olinski LE, Mathur M, Oldach D. Humoral Response to COVID-19 Vaccines and Infection during Sibeprenlimab Treatment of IgA Nephropathy: Data from the ENVISION Trial. Clin J Am Soc Nephrol. 2026 Jun 11. doi: 10.2215/CJN.0000001089. Online ahead of print.
PubMed 42275148Mathur 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.
PubMed 35570983
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03719443
- Acronym / sponsor ID
- VIS649-101
- Keywords
- chronic glomerular disease, autoimmune glomerulonephritis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Study start
- 9 Oct 2018 (actual)
- Primary completion
- 10 Aug 2019 (actual)
- Study completion
- 10 Aug 2019 (actual)
- First posted
- 25 Oct 2018 (actual)
- Results
- Posted 20 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- phase 1, randomized, placebo-controlled, double-blind, single ascending dose study
| Arm | Type | Receives |
|---|---|---|
| VIS649 | Experimental | Biological: VIS649A 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 | Biological: PlaceboSingle 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (28 listed)
- 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:
Key exclusion criteria (21 listed)
- 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).
- Subject is judged by the Investigator or the Medical Monitor to be inappropriate for the study.
- 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.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VIS649Single IV dose of study product on Day 1 of study | Biological | VIS649 |
| PlaceboSinge IV dose of placebo administered via IV on Day 1 of study | Biological | Placebo |
Primary outcome
Overall Summary of Treatment Emergent Adverse Events
Time frame: 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
34 secondary outcomes
Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants
Time frame: 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 Participant
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: Day 1 to day 112
Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants
Time frame: Day 1 to day 112
Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Time Profile. Japanese Participants
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 1 to day 112.
Vd: The Volume of Distribution of VIS649 in Serum Samples. Japanese Participants
Time frame: Day 1 to day 112.
Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. Non-Japanese Participants
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 1 to day 112.
Vd: The Volume of Distribution of VIS649 in Serum Samples. Non-Japanese Participants
Time frame: Day 1 to day 112.
Pharmacodynamic Effect of VIS649 on Total Immunoglobulin G Species. All Participants
Time frame: From baseline to Week 24
Pharmacodynamic Effect of VIS649 on Total Immunoglobulin A Species. All Participants
Time frame: From baseline to Week 24
Pharmacodynamic Effect of VIS649 on Total Immunoglobulin M Species. All Participants
Time frame: From baseline to Week 24
Pharmacodynamic Effect of VIS649 on Circulating CD16 +CD56 (Natural Killer) Cells for All Participants in Cohorts 1-4
Time frame: From baseline to Week 24
Pharmacodynamic Effect of VIS649 on Circulating CD19 (B Cells) for All Participants in Cohorts 1-4
Time frame: From baseline to Week 24
Pharmacodynamic Effect of VIS649 on Circulating CD4 T Cells for All Participants in Cohorts 1-4
Time frame: From baseline to Week 24
Pharmacodynamic Effect of VIS649 on Circulating CD3 T Cells for All Participants in Cohorts 1-4
Time frame: From baseline to Week 24
Pharmacodynamic Effect of VIS649 on Circulating CD8 T Cells for All Participants in Cohorts 1-4
Time frame: From baseline to Week 24
Summary of Anti -VIS649 Anti-drug Antibodies (ADA)
Time frame: Baseline to Day 112
Summary of Anti -VIS649 Antibody (ADA) Titer by Treatment
Time frame: Baseline to Day 112
Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants by Anti-VIS649 Status
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 112 days
Vd: The Volume of Distribution of VIS649 in Serum Samples. All Participants by Anti-VIS649 Antibody Status (Positive or Negative)
Time frame: 112 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42275148McCafferty K, Barratt J, Suzuki Y, Liew A, Rizk DV, Chacko B, Kooienga L, Lafayette R, Wong MG, Pasetti MF, Shriver MC, Follman K, Moc Willeford C, Sahay M, Honig G, Andrews L, Olinski LE, Mathur M, Oldach D. Humoral Response to COVID-19 Vaccines and Infection during Sibeprenlimab Treatment of IgA Nephropathy: Data from the ENVISION Trial. Clin J Am Soc Nephrol. 2026 Jun 11. doi: 10.2215/CJN.0000001089. Online ahead of print.
- Derived from this study: PubMed 35570983Mathur 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.
- Otsuka Clinical Trial WebsiteLink provided by the sponsor.
- Otsuka Clinical Trial TransparencyLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Esther Yoon, MD principal investigator
Parexel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VIS649 in people with Immunoglobulin A Nephropathy and IgAN - IgA Nephropathy, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Summary of Treatment Emergent Adverse Events (time frame: Baseline to day 112). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03719443, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2026.