Phase 1 Study of SAR440894 vs Placebo

This is an interventional treatment trial for Chikungunya Virus Infection focused on measuring Chikungunya Virus, dose escalation, healthy adults, Immunogenicity, Pharmacokinetics, phase 1, placebo, SAR440894 Read More

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.