Phase I Trial of Measles Vectored Chikungungya Vaccine

This study is a randomized, double-blinded, Phase 1, placebo- controlled, and dose comparison
trial to evaluate the safety, immunogenicity and schedule of MV-CHIK. Two dosage levels (5 x
10^4 or 5 x 10^5 TCID50) and 3 immunization schedules (days 1 and 29, days 1 and 85 or days 1
and 169) will be evaluated. The study will have 6 cohorts, each with 30 subjects, 25 of whom
will receive study vaccine and 5 of whom will receive placebo. Cohorts 1-3 will receive the
low dosage of the lyophilized vaccine product (5 x 10^4 TCID50) and cohorts 4-6 will receive
the high dosage (5 x 10^5 TCID50) of the lyophilized vaccine product. Each subject will
receive two study injections using one of the three dosing schedules outlined above. This
study will enroll up to 180 healthy subjects aged 18 to 45 years (inclusive). Subjects will
be counseled on the study and will then sign an informed consent prior to any study
procedures. Screening will be performed which will include evaluation of medical history,
travel history to countries with known CHIKV circulation, medication history, a physical
examination and safety laboratory evaluations. Study duration is approximately 22 months.
Subject participation duration is approximately 8-13 months. The primary objectives are to
evaluate the safety and tolerability of 5 x 10^4 TCID50 and 5 x 10^5 TCID50 MV-CHIK and
placebo following two consecutive intramuscular injections and to assess the CHIKV serum
plaque reduction neutralization test (PRNT50) antibody responses to 5 x 10^4 TCID50, 5 x 10^5
TCID50 of MV-CHIK or placebo on day 29 following the first dose. The secondary objectives are
to assess the CHIKV serum plaque reduction neutralization test (PRNT50) antibody responses to
5 x 10^4 TCID50, 5 x 10^5 TCID50 MV-CHIK and or placebo using three dose schedules (days 1
and 29, days 1 and 85, or days 1 and 169) on day 29 following the second dose, assess CHIKV
serum PRNT50 antibody responses to 5 x 10^4 TCID50, 5 x 10^5 TCID50 MV-CHIK or placebo on
days 15, 85 and 169 following the second dose of vaccine, assess the CHIKV serum ELISA
antibody responses to 5 x 10^4 TCID50, 5 x 10^5 TCID50 MV-CHIK or placebo on day 29 following
the first dose of vaccine and days 15, 29, 85 and 169 following the second dose of vaccine,
and to assess the durability of CHIKV serum ELISA and PRNT50 antibody responses to 5 x 10^4
TCID50, 5 x 10^5 TCID50 MV-CHIK or placebo on day 85 (Groups 2+5) and day 169 (Groups 3+6)
following the first dose of vaccine.

Inclusion Criteria:

Inclusion criteria must be assessed by a clinician licensed to make medical diagnoses.
Subjects must meet all of the following inclusion criteria to participate in this study

1. Males and non-pregnant females between the ages of 18 and 45 years (at study start),
inclusive.

2. Provide written informed consent before initiation of any study procedures.

3. Women of childbearing potential must agree to practice adequate contraception during
the 30 days prior to Day 1, the first injection, through 85 days after the second
study injection. A woman is considered of childbearing potential unless surgically
sterile (tubal ligation, bilateral oophorectomy, or hysterectomy) or post-menopausal
(> /= 1 year) or successful Essure placement (permanent, non-surgical, non-hormonal
sterilization) with documented confirmation test at least 3 months after the
procedure. Acceptable birth control methods include but are not limited to: abstinence
from sexual intercourse with men; monogamous relationship with a vasectomized partner;
double-barrier methods (condoms, diaphragms, spermicides; and intrauterine devices);
and licensed hormonal methods.

4. In good health, as judged by the investigator and determined by vital signs, medical
history, and a physical examination. Temperature 37.8°C, heart rate 50-110bpm
(inclusive), systolic blood pressure 85-150 mmHg (inclusive), diastolic blood pressure
55-95 mmHg (inclusive). Subjects may be on chronic or as needed (prn) medications if,
in the opinion of the site principal investigator or appropriate sub-investigator,
they pose no additional risk to subject safety or assessment of reactogenicity and
immunogenicity. NOTE: Athletically trained subjects with a pulse > \= 45 - 49 may be
enrolled if an ECG shows no evidence of first, second or third degree heart block.

5. Screening laboratory values must be within site normal limits, though trace urine
protein is acceptable. Screening labs will include: Blood hemoglobin, White blood cell
(WBC) count, Absolute neutrophil count, Platelets, Creatinine, Aspartate
Aminotransferase (AST), Alanine Aminotransferase (ALT), Bilirubin (total), Glucose
(random, must be less than 140), Urine dipstick for protein and glucose (negative to
trace protein are acceptable), Negative HIV 1/2 antibody/antigen test, Hepatitis B
surface antigen (HBsAg), and Hepatitis C virus (HCV) antibody NOTE: Creatinine values
lower than the normal range may be acceptable if the PI or a designated licensed
clinician determines that these laboratory findings are not clinically significant.
HIV and hepatitis C viral load PCR testing may be performed for individuals suspected
of having indeterminate antibody/antigen testing (Sites will use the standard HIV
testing protocol for their institution).

6. Able to understand and comply with planned study procedures and willing to be
available for all study-required procedures, visits and calls for the duration of the
study.

7. Willing to abstain from donating whole blood or blood derivatives until 90 days after
the final study injection.

8. History of measles vaccination.

Exclusion Criteria:

1. History of known chikungunya infection.

2. Previous vaccination with an investigational chikungunya vaccine.

3. Past residence in, or travel for greater than 1 consecutive month within the past 6
months to, a location known to have local CHIKV transmission. (Examples of countries
with local chikungunya virus transmission include, but are not limited to, countries
in sub-Saharan Africa, South Asia, the Indian and Pacific Ocean). Residence in or
travel to Central and South America, the Caribbean, Florida, Puerto Rico and the U.S.
Virgin islands, if prior to 2013, will be permitted.

4. Plan to travel to a location known to have local CHIKV transmission during the course
of the study or history of travel to one of these countries within 30 days prior to
screening. Travel to Florida will be permitted. Those planning travel to Florida will
be provided information on mosquito bite protection.

5. Body temperature >/ =100 °F (>/ =37.8°C) or acute illness within 3 days before study
injection days (subject may be rescheduled).

6. A positive serum or urine pregnancy test at screening or within 24 hours prior to
study injection, women who are planning to become pregnant, or women who are
breastfeeding. If female of childbearing potential as defined in Inclusion Criterion
3. From 30 days prior to entering the study until 85 days after the final study
injection.

7. Any clinically significant acute or chronic medical condition that, in the opinion of
the investigator, would preclude participation. E.g., History of seizure disorders
(other than febrile seizures as an infant), autoimmune disease, immunodeficiency, any
spleen disease, active malignancy, active asthma, known cardiac disease, pulmonary
disease, liver disease, renal disease, unstable or progressive neurological disorders,
diabetes mellitus, and transplant recipients.

8. History of thrombocytopenia, idiopathic thrombocytopenic purpura or other platelet
disorder.

9. A history of chronic arthritis or chronic arthralgia symptoms.

10. Used an immunosuppressive or immunomodulatory drug for 2 or more consecutive weeks
within 6 months prior to the first study injection (nasal and topical steroids are
allowed). Such as >/ =20 mg total dose/day of prednisone orally or > 840 µg of inhaled
beclomethasone.

11. A diagnosis of schizophrenia, bipolar disease, or history of hospitalization for a
psychiatric condition or previous suicide attempt.

12. A history of treatment for any other psychiatric disorder in the past 3 years that
increases the risk to the subject in the opinion of the investigator Treatment for
mild depression or anxiety using a single antidepressant or anti-anxiety medication
will be allowed so long as the subject has been on stable doses for 3 months.

13. Received immunoglobulin or other blood product within 3 months prior to enrollment or
planned receipt of immunoglobulin or a blood product through study day 169 following
the second dose of vaccine.

14. Received or plan to receive any live licensed vaccines within 4 weeks or inactivated
licensed vaccines within 2 weeks of any study injection.

15. Received or plans to receive measles-containing vaccine within 3 months prior to
enrollment or planned to receive through study day 29 following the second dose of
vaccine. measles, mumps, rubella vaccine.

16. History of anaphylaxis or severe allergic reaction to vaccines or history of allergic
reaction to any components in the MV-CHIK vaccine.

17. Received an experimental or investigational agent within 1 month before study
injections or expectation to receive an experimental agent through 6 months following
the last study injection. Vaccine, drug, biologic, device, blood product, or
medication.

18. Any condition that would, in the opinion of the investigator, place the subject at an
unacceptable injury risk, render him/her unable to meet the requirements of the
protocol, or that may interfere with successful study completion.

19. A history of alcohol or drug abuse during the previous 3 years For example, daily
excessive alcohol or marijuana use or frequent binge drinking as determined by the
investigator.

20. Presence of tattoos that, in the opinion of the investigator, would preclude
evaluation of the injection site.