First in Human Study to Assess Safety of VIS649 in Healthy Subjects

NCT03719443 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: VIS649-101
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, randomized, placebo-controlled, double-blind, single ascending dose study of IV VIS649 in healthy subjects. VIS649 is a monoclonal immunoglobulin G2 (IgG2) antibody targeting the B-cell growth factor APRILL. The study will enroll up to 45 subjects and will be conducted in up to 5 sequential dosing cohorts at four different dose levels, enrolling 9 subjects per cohort. Subjects will be randomized to VIS649 or placebo in a ratio of 7:2 (7 active, 2 placebo). Safety, pharmacokinetic (PK) and pharmacodynamic (PD) data from the initial cohorts will be assessed.

Conditions

Immunoglobulin A Nephropathy; IgAN - IgA Nephropathy; IgA Nephropathy

Keywords

chronic glomerular disease; autoimmune glomerulonephritis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (34)

• Cmax: Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participants

  0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.

• Tmax: Time to the Maximum Serum VIS649 Concentration Determined Directly From the Concentration-time Profile. All Participant

  0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.

• The Pharmacokinetic Exposure Profiles of VIS649 in Serum. All Participants

  0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.

• T 1/2 The Terminal Elimination Half Life of VIS649 in Serum Samples. All Participants

  0, 1, 2, 8, and 24-hours post-dose, Day 3, 7, 14, 28, 42, 56, 70, and 112.

• CL: The Clearance of VIS649 in Serum Samples Calculated Using Exposure Extrapolated to Infinity by Dose.

  Day 1 to day 112

Study Arms (2)

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.

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.

Biological: Placebo

Interventions

VIS649 BIOLOGICAL

Single IV dose of study product on Day 1 of study

VIS649

Placebo BIOLOGICAL

Singe IV dose of placebo administered via IV on Day 1 of study

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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 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.
• 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.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (1)

California Clinical Trials Medical Group

Glendale, California, 91206, United States

Location

Related Publications (1)

• 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.

  PMID: 35570983 DERIVED

Related Links

• Otsuka Clinical Trial Website
• Otsuka Clinical Trial Transparency

MeSH Terms

Conditions

Glomerulonephritis, IGA

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Principal Investigator
• Organization: Parexel International

info@parexel.com

(781) 487-9900

Study Officials

• Esther Yoon, MD

  Parexel

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: phase 1, randomized, placebo-controlled, double-blind, single ascending dose study

Study Record Dates

• First Submitted: October 10, 2018
• First Posted: October 25, 2018
• Study Start: October 9, 2018
• Primary Completion: August 10, 2019
• Study Completion: August 10, 2019
• Last Updated: May 1, 2026
• Results First Posted: March 20, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)