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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03719443
• Date of registration: 10/10/2018
• Prospective Registration: No
• Primary sponsor: Visterra, Inc.
• Public title: First in Human Study to Assess Safety of VIS649 in Healthy Subjects
• Scientific 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
• Date of first enrolment: October 9, 2018
• Target sample size: 41
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03719443
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Esther Yoon, MD
• Affiliation: Parexel

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Subject voluntarily agrees to participate in this study and signs an Institutional
Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent form
prior to performing any of the Screening Visit procedures and be able to sign and date
an appropriate Health Insurance Portability and Accountability Act (HIPAA)
authorization form or subject privacy form, if appropriate.

2. Male and female subjects between 18 to 55 years of age, inclusive, at the Screening
Visit.

3. For Japanese subjects: Subject is of Japanese descent as evidenced by verbal
confirmation of familial heritage (a subject has all four Japanese grandparents born
in Japan).

4. For non-Japanese subjects: Subjects must be of non-Asian descent, as evidenced by
verbal confirmation that all four grandparents are non-Asian.

5. The following applies to female subjects:

- Non-childbearing potential (surgically sterile [hysterectomy or bilateral tubal
ligation]) for at least 6 months, or postmenopausal = 1 year, or

- Non-pregnant, non-lactating females of childbearing potential must report prior
use (over the 28 days prior to dosing of study drug) of medically acceptable
forms of birth control (hormonal contraception, abstinence, diaphragm with
spermicide, condom with spermicide or intrauterine device, or partner with
vasectomy), with agreement to continue to use a medically acceptable form of
birth control (as described) through the end of their participation in the study.
Alternatively, a reported history of abstinence beginning at least 28 days prior
to study drug dosing, with agreement to continue abstinence through the end of
their participation in the study are required. Females of childbearing potential
must also have a negative serum human chorionic gonadotropin (hCG) pregnancy test
at Screening and a negative urine hCG pregnancy test at Baseline (Day -1). Female
subjects must also agree not to donate eggs/bank eggs for the duration of their
participation in the study.

6. For male, subject and/or his partner must use a highly effective form of contraception
(i.e., double-barrier as described above, have had a vasectomy, or have a female
partner of non childbearing potential) or agree to abstinence following study drug
dosing, through the end of the subject's participation in the study. Male subjects
must also agree to not donate sperm for the duration of their participation in the
study, following study drug dosing.

7. Screening laboratory values must meet the following criteria:

- White blood cells 3,000 12,000/mm3

- Platelets >150,000/mm3

- Hemoglobin >13 gm/dL for male and>11 gm/dL for female

- Estimated glomerular filtration rate >80 mL/min/1.73 m2

- Serum creatinine <1.25x Upper Limit of Normal (ULN)

- Blood Urea Nitrogen (BUN) =25mg/dL

- Aspartate aminotransferase (AST) =50 U/L

- Alanine aminotransferase (ALT) =67 U/L

- Alkaline phosphatase =150 U/L

- Total Bilirubin =1.4 mg/dL unless patient has Gilbert Syndrome, in which case
direct bilirubin must be within normal range

- Glucose (fasting) <115 mg/dL

- Drug and alcohol screen Negative

- Serum Immunoglobulin G (IgG) >750 mg/dL (7.5 g/L)

- Serum Immunoglobulin M (IgM) >55 mg/dL (0.55 g/L)

- Serum IgA >80 mg/dL (0.8 g/L)

8. Body mass index (BMI) between 18 and 32 kg/m2, inclusive, at the Screening Visit.

9. Healthy, determined by pre-study medical evaluation (medical history, physical
examination, vital signs, 12-lead ECG, and clinical laboratory evaluations), as judged
by the Investigator.

10. Is willing and able to comply with study restrictions and to remain at the central
processing unit (CPU) for the in-patient duration of the study and return for all
follow-up outpatient visits.

11. QTcF or QTcB < 450 msec at Screening (may be repeated once).

Exclusion Criteria:

1. Is participating in another clinical study of any investigational drug, device, or
intervention or has received any investigational medication during the last 30 days or
five half-lives, whichever is longer, before Baseline (Day -1).

2. Subject is judged by the Investigator or the Medical Monitor to be inappropriate for
the study.

3. Subject has a history or current evidence of a serious and/or unstable cardiovascular,
respiratory, gastrointestinal, hematologic, autoimmune, blood dyscrasias or other
medical disorder, including psychiatric disorders, cirrhosis or malignancy. History of
minor skin cancers (not including melanoma) or surgically treated, limited cervical
carcinomas (i.e., carcinoma in situ) are not exclusionary.

4. Subject has a history or presence of proteinuria, chronic kidney disease, disease
requiring immunosuppressive therapy (including systemic steroids), or is considered to
be immunosuppressed for any other reason.

5. Previous receipt of antibody or biologic therapy whether licensed or investigational
(immunoglobulin products, monoclonal antibodies or antibody fragments) within 30 days
prior to dosing or 5 half-lives within the dose of Investigational medicinal products
(IMP), whichever is longer.

6. History of a previous severe allergic reaction with generalized urticaria; angioedema
or anaphylaxis.

7. Blood pressure >160/100 mmHg or <90/50 mmHg (may be repeated once if abnormal), at the
Screening visit and Day 1.

8. Known hypoglobulinemia disorder (i.e., common variable immunodeficiency), X linked
agammaglobulinemia, selective IgA deficiency, selective IgM deficiency).

9. History of pre-existing latent infections (e.g., tuberculosis) or any infection
requiring hospitalization or treatment with antivirals or antibiotics, or vaccination
within 30 days prior to administration of study medication.

10. Concomitant use of marketed or investigational systemic immunosuppressive or
immunomodulatory medications (e.g., corticosteroids, methotrexate, azathioprine, etc.
and/or biologics) is prohibited and require a washout period prior to Screening (30
days or 5 half lives, whichever is longer).

11. Has received any prescription or non-prescription (over-the-counter [OTC]) except
acetaminophen or ibuprofen, including hormonal contraceptives, topical medications,
vitamins, dietary or herbal during the last 30 days o


Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

IgAN - IgA Nephropathy

Immunoglobulin A Nephropathy

IgA Nephropathy

Intervention(s)

Biological: VIS649

Biological: Placebo

Primary Outcome(s)

Number of participants with treatment-emergent adverse events [Time Frame: 112 days]

Frequency of 12-lead ECG treatment emergent abnormalities [Time Frame: 112 days]

Secondary Outcome(s)

The levels of anti-drug antibodies [Time Frame: 112 days]

The PK profile of VIS649 in serum/blood samples [Time Frame: 112 days]

The effect of VIS649 on pharmacodynamic (PD) parameters [Time Frame: 112 days]

Secondary ID(s)

VIS649-101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors