A single, ascending-dose design with five dose-cohorts of 8 subjects. Forty healthy adults aged 18 to 45, inclusive, will be recruited and admitted at one US site. Each subject will be randomized to receive either SAR440894 or matching placebo via 60-minute intravenous infusion. In each cohort of 8 subjects, the randomization ratio will be 6 active to 2 placebo, and 2 sentinel subjects (one from each active and placebo group) will be dosed first. Dosing of the next dose-cohort will be dependent on acceptable meeting predefined safety criteria in the preceding cohort. Each subject's participation will take place over approximately 150 days, not including the screening visit. There are no hypotheses for this phase I study. The primary objective will be to determine the safety of single ascending intravenous (IV) infusions of SAR440894 when administered in healthy adults.
A single, ascending-dose design with five dose-cohorts of 8 subjects. Forty healthy adults
aged 18 to 45, inclusive, will be recruited and admitted at one US site. Each subject will be
randomized to receive either SAR440894 or matching placebo via 60-minute intravenous
infusion. In each cohort of 8 subjects, the randomization ratio will be 6 active to 2
placebo, and 2 sentinel subjects (one from each active and placebo group) will be dosed
first. Dosing of the next dose-cohort will be dependent on acceptable meeting predefined
safety criteria in the preceding cohort. Each subject's participation will take place over
approximately 150 days, not including the screening visit. There are no hypotheses for this
phase I study. The primary objective will be to determine the safety of single ascending
intravenous (IV) infusions of SAR440894 when administered in healthy adults. The secondary
objectives are: 1) to determine the pharmacokinetics (PK) of single ascending doses of
60-minute IV infusions SAR440894 in healthy adults and 2) to asses the immunogenicity of
single ascending doses of 60-minute IV infusions SAR440894 in healthy adults.
Other: Placebo
One time 60-minute IV infusion of lyophilized placebo for SAR440894
Biological: SAR440894
One time 60-minute IV infusion of SAR440894 monoclonal antibody (IgG1) directed against the E2 envelope protein of chikungunya virus
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 30 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 (Essure(R)) with documented radiographic confirmation at
90 days; (d) effective intrauterine device (IUD); (e) hormonal implants (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 at any point during the follow-up period.
https://www.cdc.gov/chikungunya/geo/index.html
Exclusion Criteria:
1. Has any medical condition (e.g., renal dysfunction) that, in the opinion of the site
PI or appropriate sub-investigator listed on Food and Drug Administration (FDA) Form
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 FDA Form 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 30 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 30 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.
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 median QTcF greater than 450 msec or females with a median QTcF greater
than 460 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 median 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 screen for hepatitis B virus surface antigen, hepatitis C virus antibody, or
human immunodeficiency virus (HIV) antibody.
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 30 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; lower limit values of 133-134 mmol/L will be allowed at Screening and Day
-1/baseline. If the result at screening is 132 mmol/L or below , the participant will
be scheduled to repeat the test during the screening period but before Day-1 to assure
that it is at or > 133 mmol/L Repeated sodium values of 132 mmol/L and below are
exclusionary. Potential subjects excluded prior to Protocol Version 6.0 with Grade 1
sodium values may be rescreened.
For hemoglobin; a lower limit of 13.5 g/dL for males and 11.5 mg/dL for females is
allowable at Screening. Hemoglobin values of 13.4 mg/dL and below for males and 11.4
mg/dL and below for females are exclusionary at Screening.
For total bilirubin; upper limit values of 1.2 mg/dL will be allowed at Screening and
Day -1/baseline provided the AST and ALT are within normal limits. Total bilirubin
values of 1.3mg/dL and above are exclusionary. Potential subjects excluded prior to
Protocol Version 6.0 with bilirubin values below the Version 6.0 upper limit may be
rescreened.
**Grade 1 or higher toxicity, see Appendix C or Appendix D. 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.
22. Potassium, bicarbonate or creatinine results are Grade 1 or higher at either Screening
or Day -1/Baseline visits.
23. Received an experimental agent (vaccine, drug, biologic, device, or medication) within
30 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 at Screening.
27. Has received blood products within 120 days prior to Screening.
28. Has received any mAb in the past, whether licensed or investigational, or plans to
receive a mAb during the study.
Johnson County Clin-Trials (JCCT)
Lenexa, Kansas, United States
Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit
Durham, North Carolina, United States
Michael Cohen-Wolkowiez
19196688812
michael.cohenwolkowiez@duke.edu