Safety and Immunogenicity Study of a Ross River Virus (RRV) Vaccine

Study Overview
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Brief Summary
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The primary objective of this study is to assess the safety and tolerability of the Ross River Virus (RRV) Vaccine in a healthy young adult population. Other objectives of this study are to assess the immunogenicity of the RRV Vaccine in a healthy young adult population and to identify the optimal dose level of the RRV Vaccine in a healthy young adult population.

Official Title
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A Blinded Phase 1/2 Dose Escalation Study to Assess Safety and Immunogenicity and Investigate the Optimal Dose Level of a Formalin-Treated, UV-Inactivated, Vero Cell-Derived Ross River Virus (RRV) Vaccine in Healthy Volunteers Aged 18 to 40 Years

Conditions
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Ross River Virus Disease (RRVD)

Intervention / Treatment
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* Biological: Formalin-treated, UV-inactivated, whole-virion, Vero cell-derived, preservative free Ross River Virus (RRV) vaccine with or without an Al(OH)3 adjuvant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are 18 to 40 years of age, inclusive, on the day of screening; Have an understanding of the study and its procedures, agree to its provisions, and give written informed consent prior to study entry; Are generally healthy; Are physically and mentally capable of participating in the study and following study procedures; Agree to keep a daily record of symptoms for the duration of the study; If female of childbearing potential - have a negative urine pregnancy test result within 24 hours of the scheduled first vaccination and agree to employ adequate birth control measures for the duration of the study. Exclusion Criteria: Have a history of RRV exposure or a history of travel to a RRV endemic area: Australia, West Papua, Papua New Guinea, Solomon Islands, New Caledonia, Fiji Islands, Samoa Islands and Cook Island; Have a Body Mass Index > 35; Have an elevated blood pressure at screening of > 159 mmHg systolic and/or > 99 mmHg diastolic while seated and at rest and confirmed by two additional measurements taken at least 30 minutes apart (while seated and at rest); Have clinically significant abnormal clinical laboratory values at screening; Have clinically significant electrocardiographic abnormalities at screening; Test positive for Human Immunodeficiency Virus (HIV), Hepatitis B Surface Antigen (HbsAg) or Hepatitis C Virus (HCV); Have a history of cardiovascular disease; Have a history of immunodeficiency or autoimmune diseases; Have a history of arthritis (joint swelling, tenderness, warmth or erythema) on more than one occasion, not related to trauma (including running) or any episode of non-trauma related arthritis within the previous 6 months; Have an active neoplastic disease or have a history of hematological malignancy; Have a disease or are undergoing a form of treatment that can be expected to influence immune response. Such treatment includes, but is not limited to, systemic or high dose inhaled (> 800 mg/day of beclomethasone dipropionate or equivalent), corticosteroids, radiation treatment or other immunosuppressive or cytotoxic drugs; Have a history of inflammatory or degenerative neurological disease (eg Guillain Barré, multiple sclerosis); Have received any vaccination within 2 weeks prior to vaccination in this study; Have received a blood transfusion or immunoglobulins within 30 days prior to vaccination in this study; Have donated blood or plasma within 30 days prior to vaccination in this study; Have a history of any vaccine related contraindicating event (eg, anaphylaxis, allergy to components of the test vaccine, other known contraindications); Have a rash, dermatologic condition or tattoos which may interfere with injection site reaction rating; Have a positive urine drug screen, (unless the detected drug is currently prescribed by a licensed health care provider and the continued administration of the drug would not otherwise exclude the subject from participation); Were administered an investigational drug within 6 weeks prior to study entry; Are concurrently participating in a clinical study that includes the administration of an investigational product; Are a member of the team conducting this study; Are in a dependent relationship with one of the study team members. Dependent relationships include close relatives (ie, children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting the study; If female, are pregnant or lactating.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1, Treatment Arm 1<br>Randomization of a total of approx. 200 subjects to one of four treatment arms at 1:1:1:1 ratio to receive 1.25 µg of the RRV Vaccine with/without adjuvant (Al(OH)3), or 2.5 µg of the RRV Vaccine with/without adjuvant (Al(OH)3). Cohort 1 is subdivided into Cohort 1a (n = 60, i.e. 15 subjects per dose/adjuvantation combination) to receive the first vaccination on Day 0, with Day 7 safety data being reviewed by a Data Monitoring Committee and, following DMC recommendation, to receive the second vaccination at Day 21; Cohort 1b (n=140, i.e. 35 subjects per dose/adjuvantation combination) is to be vaccinated twice 21 days apart upon availability of DMC recommendation. Booster vaccination to follow 180 days after first vaccination. | Biological: Formalin-treated, UV-inactivated, whole-virion, Vero cell-derived, preservative free Ross River Virus (RRV) vaccine with or without an Al(OH)3 adjuvant<br>* Two intramuscular injections of either 1.25 µg, 2.5 µg, 5 µg or 10 µg on Days 0 and 21, with a booster vaccination to follow 180 days after the first.<br>|
| Experimental: Cohort 1, Treatment Arm 2<br>Same as Cohort 1, Treatment Arm 1 | Biological: Formalin-treated, UV-inactivated, whole-virion, Vero cell-derived, preservative free Ross River Virus (RRV) vaccine with or without an Al(OH)3 adjuvant<br>* Two intramuscular injections of either 1.25 µg, 2.5 µg, 5 µg or 10 µg on Days 0 and 21, with a booster vaccination to follow 180 days after the first.<br>|
| Experimental: Cohort 1, Treatment Arm 3<br>Same as Cohort 1, Treatment Arm 1 | Biological: Formalin-treated, UV-inactivated, whole-virion, Vero cell-derived, preservative free Ross River Virus (RRV) vaccine with or without an Al(OH)3 adjuvant<br>* Two intramuscular injections of either 1.25 µg, 2.5 µg, 5 µg or 10 µg on Days 0 and 21, with a booster vaccination to follow 180 days after the first.<br>|
| Experimental: Cohort 1, Treatment Arm 4<br>Same as Cohort 1, Treatment Arm 1 | Biological: Formalin-treated, UV-inactivated, whole-virion, Vero cell-derived, preservative free Ross River Virus (RRV) vaccine with or without an Al(OH)3 adjuvant<br>* Two intramuscular injections of either 1.25 µg, 2.5 µg, 5 µg or 10 µg on Days 0 and 21, with a booster vaccination to follow 180 days after the first.<br>|
| Experimental: Cohort 2, Treatment Arm 1<br>Randomization of a total of approx. 100 subjects to one of two treatment arms at 1:1 ratio to receive 5 µg of the RRV Vaccine with/without adjuvant (Al(OH)3). Vaccinations take place upon review of Cohort 1a Day 7 safety data by DMC and recommendation to proceed. Booster vaccination to follow 180 days after first vaccination. | Biological: Formalin-treated, UV-inactivated, whole-virion, Vero cell-derived, preservative free Ross River Virus (RRV) vaccine with or without an Al(OH)3 adjuvant<br>* Two intramuscular injections of either 1.25 µg, 2.5 µg, 5 µg or 10 µg on Days 0 and 21, with a booster vaccination to follow 180 days after the first.<br>|
| Experimental: Cohort 2, Treatment Arm 2<br>Same as Cohort 2, Treatment Arm 1 | Biological: Formalin-treated, UV-inactivated, whole-virion, Vero cell-derived, preservative free Ross River Virus (RRV) vaccine with or without an Al(OH)3 adjuvant<br>* Two intramuscular injections of either 1.25 µg, 2.5 µg, 5 µg or 10 µg on Days 0 and 21, with a booster vaccination to follow 180 days after the first.<br>|
| Experimental: Cohort 3, Treatment Arm 1<br>Randomization of a total of approx. 100 subjects to one of two treatment arms at 1:1 ratio to receive 10 µg of the RRV Vaccine with/without adjuvant (Al(OH)3). Vaccinations take place upon review of Cohort 1b and Cohort 2 Day 7 safety data by DMC and recommendation to proceed. Booster vaccination to follow 180 days after first vaccination. | Biological: Formalin-treated, UV-inactivated, whole-virion, Vero cell-derived, preservative free Ross River Virus (RRV) vaccine with or without an Al(OH)3 adjuvant<br>* Two intramuscular injections of either 1.25 µg, 2.5 µg, 5 µg or 10 µg on Days 0 and 21, with a booster vaccination to follow 180 days after the first.<br>|
| Experimental: Cohort 3, Treatment Arm 2<br>Same as Cohort 3, Treatment Arm 1 | Biological: Formalin-treated, UV-inactivated, whole-virion, Vero cell-derived, preservative free Ross River Virus (RRV) vaccine with or without an Al(OH)3 adjuvant<br>* Two intramuscular injections of either 1.25 µg, 2.5 µg, 5 µg or 10 µg on Days 0 and 21, with a booster vaccination to follow 180 days after the first.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of subjects with fever with onset within 7 days after the first and 7 days after the second vaccination |  | Within 7 days after the first and second vaccinations | 
| Immune response measured by RRV-specific IgG titer 21 days after the second vaccination |  | 21 days after the second vaccination |