Safety and Tolerability of CV8102 Alone and in Combination With a Rabies Virus Vaccine in Healthy Adults

Study Overview
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Brief Summary
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The purpose of this clinical trial is to investigate the safety and tolerability of IM administered CV8102 and an IM administered combination of CV8102 and rabies vaccine in humans.

Official Title
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Phase I Safety and Tolerability Trial of Single and Repeat Doses of the RNA-based Adjuvant CV8102 Alone and in Combination With a Licensed Rabies Virus Vaccine in Healthy Adults

Conditions
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Rabies

Intervention / Treatment
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* Biological: CV8102
* Biological: Rabipur
* Biological: CV8102 + Rabipur


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Compliant with protocol procedures and available for clinical F/U until the protocol-defined end of the trial Physical examination and laboratory results without clinically significant findings Body Mass Index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 Subjects must use reliable forms of contraception (barrier method with spermicidal agent or true abstinence) and must refrain from sperm donation during treatment and the 4-week F/U period after the last treatment. Exclusion Criteria: Use of any investigational or non-registered product (adjuvant, drug) other than CV8102 within 4 weeks preceding the administration of the CV8102, or planned use of any such agent during the trial period Subject has received any licensed or non-licensed vaccines within 4 weeks prior to the administration of CV8102 alone or in combination with the licensed rabies vaccine or planned vaccinations during the trial period Any treatment with immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of CV8102 alone or in combination with the licensed rabies vaccine. The use of inhaled and nasal steroids, as well as topical steroids outside the vaccination area, will be permitted Any medically diagnosed or suspected immune deficient condition based on medical history and physical examination History of autoimmune disease or suspected autoimmune disease based on medical history and physical examination that cannot be ruled out based on further examinations Administration of immunoglobulins (Igs) and/or any blood products within the 3 months preceding the administration of CV8102 or licensed rabies vaccine Acute disease at the time of enrolment. Acute disease is defined as the presence of any acute condition including but not limited to non-febrile or febrile common colds, urinary tract infections, inflammatory, allergic or traumatic conditions that may interfere with safety assessment of the investigational products Presence or evidence of significant acute or chronic disease, in particular heart disease including coronary artery disease and chronic pulmonary diseases (e.g., chronic obstructive pulmonary disease [COPD]); uncontrolled medical or psychiatric illness (subjects with uncomplicated chronic diagnoses stable and treated for ≥ 3 months e.g., mild hypertension well-controlled with medication, may be enrolled - provided the condition and its therapy are known not to be associated with an immunocompromised state or an autoimmune disease) Major congenital defects Known allergy to any component (or closely related substance) of the licensed rabies vaccine product Known type I allergy to beta-lactam antibiotics Evidence of current alcohol or drug abuse History of any neurological disorders or seizures Known seropositivity for human immunodeficiency virus (HIV), hepatitis B virus (HBV) (except in subjects previously vaccinated against HBV) or hepatitis C virus (HCV) Foreseeable non-compliance with protocol as judged by the Investigator History of any life-threatening anaphylactic reactions Subjects with impaired coagulation in whom an IM injection is contraindicated. Additional exclusion criteria for subjects participating in the (adjuvanted) rabies vaccination part: Subject has previously received any investigational or licensed rabies vaccine Intending to travel to regions/countries for which rabies vaccinations are recommended or where high risk of infection exists according to travel recommendations by the German Society of Tropical Medicine and International Health (DTG) during the trial and F/U period Subject is taking chloroquine for malaria treatment or prophylaxis.

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

Sexes Eligible for Study
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Male

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CV8102<br> | Biological: CV8102<br>* Subjects will receive 2 intramuscular doses of CV8102 given 21 days apart<br>|
| Active Comparator: Rabipur<br> | Biological: Rabipur<br>* Subjects will receive 2 intramuscular doses of Rabipur given 21 days apart<br>|
| Experimental: CV8102 + Rabipur<br> | Biological: CV8102 + Rabipur<br>* Subjects will receive 2 intramuscular doses of CV8102+Rabipur given 21 days apart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with serious and non serious adverse events |  | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) of CV8102 within the dose range of 25 µg to 250 µg. |  | Up to day 49 | 
| MTD of CV8102 in combination with rabies vaccine |  | Up to Day 49 | 
| Vaccination-elicited serum rabies VNTs among the dose groups |  | Up to day 35 | 
| Vaccination-elicited innate and adaptive immune responses | Evaluation of corresponding serum and blood parameters (e.g. relevant cytokines, chemokines, immune effector molecules and lymphocyte phenotyping) | Up to Day 35 |