| Eligibility |
Inclusion Criteria:
1. Must be a healthy adult 18 to 45 years of age, inclusive, with a body mass index (BMI)
greater than 18 or less than 35 kg/m^2, inclusive.
2. Participants of childbearing potential* having vaginal intercourse must use an
effective method of contraception** from 45 days before study product administration
through the final study visit.
*Not sterilized via hysterectomy or bilateral oophorectomy and/or salpingectomy or be
less than 1 year from the last menses if menopausal.
**Includes any of the following (a) exclusive non-male sexual relationships; (b)
monogamous relationship with vasectomized partner (greater than or equal to 180 days
between procedure and subject receipt of investigational product); (c) bilateral tubal
ligation or tubal occlusion (eg., Essure(R)); (d) effective intrauterine device (IUD);
(e) hormonal implants (eg., Implanon(R)); (f) other hormonal contraceptives (such as
birth control pills, vaginal rings, patches or injections); (g) barrier methods
(condom, diaphragm, cervical cap) PLUS spermicide (gel or foam)
3. Women of childbearing potential must agree not to donate ova or oocytes (ie, human
eggs) during the study.
4. Male subjects (including those with vasectomies) whose partners are of childbearing
potential should use condoms with spermicide and not donate sperm for the duration of
the study.
5. Must have adequate venous access for IV infusions and blood draws.
6. Agrees to be available for all study visits and willing to cooperate fully with the
requirements* of the study protocol.
*Requirements include remaining in confinement for at least 72 hours after receiving
study product and other activities outlined in the protocol's Schedule of Events.
7. Is able to understand the informed consent process and procedures and signs the
consent form.
8. Will agree not to donate any blood or blood products* for the duration of the study.
- Includes whole blood, red blood cells, platelets, plasma, or plasma derivatives.
9. Will agree to avoid travel to endemic areas (as defined by the Center for Disease
Control (CDC)) for Chikungunya Virus (CHIKV) at any point during the Follow-up period
(https://www.cdc.gov/chikungunya/geo/index.html).
Exclusion Criteria:
1. Has any medical condition (renal dysfunction) that, in the opinion of the site PI or
appropriate sub-investigator listed on Form Food and Drug Administration (FDA) 1572,
is a contraindication to study participation.
2. Has any clinically significant (CS) electrocardiogram (ECG) abnormalities in the
opinion of the site Principal Investigator (PI) or appropriate sub-investigator been
listed on Form FDA 1572.
3. Use of any prohibited prescription medication (excluding contraceptives in females)
within 14 days before study product administration, through Day 56** *Prohibited
medications include immunosuppressives; immune modulators; oral corticosteroids
(topical/intranasal steroids are acceptable); prescription Non-Steroidal
Anti-inflammatory Drugs (NSAIDs); anti-neoplastic agents; any vaccine (licensed or
investigational). If study activities overlap with the influenza season, subjects will
be instructed to obtain influenza vaccine at least 45 days prior to proposed dosing or
delay vaccination until after Day 56. Subjects will be instructed to obtain the last
dose of any vaccine for SARS-CoV-2 (COVID-19) at least 45 days prior to proposed
dosing or delay vaccination until after Day 56.
4. Use of nonprescription systemic drugs within 7 days before study product
administration (includes vitamins, antacids*, over-the-counter drugs**, herbal/dietary
supplements, etc.) through Day 28***
*Nonprescription drugs and supplements may be allowed before Day 28 at the discretion
of the site PI.
**Includes proton pump inhibitors and H2-blockers (Histamine-2 blockers)
***Nonprescription drugs and supplements may be allowed before Day 28 at the
discretion of the site PI. In the event an OTC oral contraceptive becomes available
during the course of the study, it must be reviewed and approved by the site PI.
5. Hypertension, with confirmed systolic blood pressure (BP) greater than 140 mm Hg or
confirmed diastolic BP greater than 90 mm Hg, measured after 5 minutes of rest at
Screening.
6. Hypotension, with confirmed systolic BP less than 90 mm Hg.
7. Resting heart rate (HR) less than 45 bpm or greater than 100 bpm at Screening.
8. Body weight less than 50 kg.
9. History of a significant illness, per the investigators' clinical judgment, within 2
weeks before dosing (subjects can screen after illness is resolved for 2 weeks).
10. Known diagnosis of prolonged QT interval, congenital long QT syndrome,
bradyarrhythmias, or uncompensated heart failure.
11. Males with a mean QTcF greater than 450 msec or females with a mean QTcF greater than
470 msec (Fridericia's correction) at Screening.*
*ECG tracings should be recorded at least 1 minute apart, after at least 5 minutes of
rest in the supine position. If the mean QTcF value from the 3 tracings exceeds the
limits stated, the subject is disqualified.
12. Any history of malignancy ever, except low-grade skin cancer (ie, basal cell carcinoma
thought to be cured).
13. History of drug abuse, alcohol abuse, or significant psychiatric history according to
the investigators' judgment within 12 months before Screening.
14. Positive for hepatitis B virus surface antigen, hepatitis C virus antibody, or human
immunodeficiency virus (HIV) antibody at Screening.
15. Excessive consumption of beverages containing xanthine bases, or more than 400 mg of
caffeine per day within 1 week of study product administration through the final study
visit.
16. Consumption of alcohol within 24 hours before study product administration.
17. Use of nicotine-containing products within 45 days before study product administration
through the final study visit.
18. Positive drug screen*, positive cotinine screen, or positive breathalyzer test for
alcohol at Screening or admission (Day -1).
*Cannabinoids, amphetamines, barbiturates, cocaine, opiates, benzodiazepines and
phencyclidine. Subjects should be notified by phone not to consume any poppy seeds
within 24 hours before the Screening urine test to avoid a false positive opioid test
result.
19. If female, serum positive pregnancy test at Screening or serum positive pregnancy test
on Day -1.
20. Breastfeeding throughout the duration of the study
21. Total WBC and platelet counts, hemoglobin*, total bilirubin*, alanine/aspartate
aminotransferase* and sodium* are Grade 1 or higher** at Screening visit***.
*For sodium; potential subjects excluded prior to Protocol Version 6.0 with Grade 1
sodium values may be rescreened.
For hemoglobin; a lower limit within 0.5 g/dL of the lower limit of normal (LLN) is
allowable at Screening.
For total bilirubin; ULN values will be allowed at Screening and Day -1/baseline
provided the AST and ALT are within normal limits. Potential subjects excluded prior
to Protocol Version 6.0 with bilirubin values below the Version 6.0 upper limit may be
rescreened.
- For ALT/AST; subjects who screened prior to Protocol Version 11.0 were excluded
if AST/ALT results were Grade 1 or higher at Screening. Subjects who screen with
Protocol Version 11.0, AST/ALT is exclusionary if Screening results are 1.5 × ULN
or if assessed as CS by the site PI.
- Grade 1 or higher toxicity, see Appendix C and Appendix D for subjects who
screened and enrolled prior to Protocol Version 11.0. Subjects who screen and
enroll with Protocol Version 11.0, toxicity will be assessed with the NCI CTCAE,
Version 5.0 - November 2017. Safety laboratory tests drawn on Day -1 or Screening
if within 48 hours of planned dosing will serve as baseline values. Day -1
laboratory tests with a Grade 1 severity, other than those noted above, will not
exclude subjects from participation.
- All other abnormal laboratory values collected at Screening and on Day -1
will be exclusionary at the discretion of the PI.
22. Potassium, bicarbonate or creatinine/eGFR* results are Grade 1 or higher at either
Screening or Day -1/Baseline visits.
*For creatinine; subjects who screened prior to Protocol Version 11.0 were excluded if
creatinine results were Grade 1 or higher. Subjects who screen with Protocol Version
11.0, creatinine is not an exclusionary criterion, instead subjects should have a
calculated eGFR using Chronic Kidney Disease Epidemiology Collaboration Creatinine
Equation (CKD-EPI) of >/= 90 mL/min/1.73m2 to be enrolled in the study.
23. Received an experimental agent (vaccine, drug, biologic, device, or medication) within
45 days or 5 half-lives (whichever is longer) before study product administration.*
*Prior participation at any time in noninvasive methodology trials in which no drugs
were given is acceptable.
24. Is participating in or plans to participate in another clinical trial with an
interventional agent that will be received during this trial.
25. Has donated more than 500 mL of blood or blood products* within the month before
Screening.
*Includes whole blood, red blood cells, platelets, plasma, or plasma derivatives.
26. Has a history of serologically-proven Chikungunya virus (CHIKV) exposure at any point,
or positive anti CHIKV antibodies (ie., positive IgM or IgG) at Screening.
27. Has received blood products within 120 days prior to Screening.
28. Has received mAb in the past 3-months or 5 half-lives (whichever is longer) prior to
Screening, whether licensed or investigational, or plans to receive a mAb outside of
this study.
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