A Study to Evaluate the Safety and Ability of the Vaccine to Induce Antibodies Against the Respiratory Syncytial Virus in Healthy Adults

A Phase 1 Randomized, Observer Blind, Placebo Controlled, Dosage-Escalation Single Center Study to Evaluate the Safety and Immunogenicity of an RSV Fusion Glycoprotein (F) Subunit Vaccine in Healthy Adults

The purpose of this study is to evaluate the safety and immunogenicity of two doses of the investigational RSV F subunit vaccine administered intramuscularly (IM). In this current Phase 1, first-in-human study, the three different antigen amounts that have been selected will be evaluated in a stepwise manner in three different cohorts (Cohort 1: low dosage of RSV F subunit vaccine, Cohort 2: middle dosage of RSV F subunit vaccine, and Cohort 3: high dosage of RSV F subunit vaccine). In addition, the effect of an adjuvant, either aluminum hydroxide or MF59, and antibody kinetics post-vaccination at different time points will be evaluated as compared to unadjuvanted RSV F subunit vaccine at the same dosage levels.

Inclusion Criteria:

1. Healthy males and non-pregnant females 18 to 45 years of age at time of enrollment.
2. Individuals who have given written consent after the nature of the study has been explained according to local regulatory requirements.
3. Individuals in good health as determined by the outcome of the medical history, physical examination and clinical judgment of the investigator.
4. Individuals who can comply with the study procedures and are available for follow up.

Exclusion Criteria:

1. Individuals with any severe chronic or acute disease.

2. Individuals with a history of illness or with an ongoing illness that may pose additional risk to the subject if he/she participates in the study, including the following:

   • History of any chronic respiratory illness, including current diagnosis of asthma within 2 years, exercise induced wheezing, reactive airway disease, emphysema, chronic bronchitis, cystic fibrosis or chronic obstructive pulmonary disease (COPD).
   • Any respiratory illness within 7 days prior to receiving the first study injection.
   • Any active pulmonary infection or other inflammatory conditions, even in the absence of febrile episodes, within 14 days prior to the first study injection.
   • Hepatitis B or hepatitis C infection.

3. Individuals who have had a malignancy or lymphoproliferative disorder within the past 5 years.

4. Individuals with known or suspected impairment of the immune system including but not limited to HIV, autoimmune disorders, immunosuppressive therapy, and diabetes mellitus.

5. Individuals with any history of progressive or severe neurologic disorder, seizure disorder or Guillian-Barré syndrome.

6. Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.

7. Individuals with a BMI > 35 kg/m2. BMI is to be calculated by the following formula: subject weight at baseline divided by subject height in meters multiplied by the subject height in meters. The numerical result will be rounded to the nearest 0.1.

8. Individuals who are allergic to any of the vaccine components, or with a history of anaphylaxis after vaccination.

9. Individuals who during the 90 days prior to enrollment receive any medications or other treatments that may adversely affect the immune system such as allergy injections, immune globulin, interferon, immunomodulators, cytotoxic drugs or other drugs known to be frequently associated with significant major organ toxicity.

10. Individuals who receive systemic immunosuppressive agents including steroids. Prior corticosteroid therapy should be discontinued 28 days prior to enrollment. Individuals using inhaled or topical corticosteroids will be permitted.

11. Receipt or donation of blood or blood products 8 weeks prior to vaccination or planned receipt or donation during the study period.

12. Individuals participating in any clinical trial with another investigational product 28 days prior to receiving the first study vaccination or intent to participate in another clinical study at any time during the conduct of this study.

13. Individuals who have received any vaccine 28 days prior to enrollment in this study, or who plan to receive any non-study vaccines within 28 days of the second dose of study vaccine.

14. Individuals with any clinically significant abnormal safety laboratory result, as judged by the investigator.

15. If female, 'of childbearing potential', sexually active and has not used any of the 'acceptable contraceptive methods' for at least two months prior to study entry.

    Childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: menopausal for at least two years; sterile status after bilateral tubal ligation for at least one year, immediately after bilateral oophorectomy or after hysterectomy.

    Acceptable methods of birth control are defined as one or more of the following:

    • Hormonal contraceptives.
    • Barrier each and every time during intercourse.
    • Intrauterine device (IUD).
    • Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least six months prior to subject's study entry.

16. If female subject of childbearing potential and have a positive urine pregnancy test prior to study vaccinations, or are currently lactating.

17. If female of childbearing potential and sexually active, refusal to use an 'acceptable contraceptive method' through to three weeks after last study vaccination.

18. Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the subject's ability to participate in the study.

19. Individuals with a history of drug or alcohol abuse within the past 2 years.

20. Individuals who are acting as study personnel or immediate family members or the spouse of study personnel.

21. Individuals with a body temperature ≥38 °C (≥100.4◦F) within 3 days of intended study vaccination.

22. Individuals with any condition that, in the opinion of the investigator, would interfere with the primary study objectives.