A Study to Assess the Safety, Reactogenicity and Immune Response of CureVac's Candidate Rabies mRNA Vaccine in Healthy Adults

Study Overview
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Brief Summary
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Rabies infection is a disease that is caused by a virus and which is transmitted in many countries by rabid animals (dogs, monkeys, bats, etc.) through bites, scratches or licking of wounds. In most cases, humans die from it once the disease has broken out. CV7202 is a new vaccine which has not yet been studied in humans and does not consist of virus protein. Instead, the building block for the protein in the form of a so-called messenger RNA (mRNA) will be used. All living organisms have mRNA in their body. mRNA is the carrier of the information that the cells require to form proteins. In this study, mRNA that carries the information for the formation of the rabies virus protein called RABV-G will be injected into the muscle. Following the vaccination, the vaccinated individual's own cells will produce the RABV-G protein. The immune system recognizes the protein and an immune response is triggered. This clinical study will assess the safety, reactogenicity and immunogenicity of CV7202 mRNA-rabies vaccine in healthy adults.

Official Title
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A Non-Randomized, Open Label, Controlled, Dose-Escalation, Phase I Clinical Trial to Evaluate the Safety, Reactogenicity and Immunogenicity of One or Two Administrations of Candidate Rabies mRNA Vaccine CV7202 in Healthy Adult Subjects

Conditions
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Rabies

Intervention / Treatment
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* Biological: Rabipur®
* Biological: Rabies mRNA vaccine CV7202 Dose level 1
* Biological: Rabies mRNA vaccine CV7202 Dose level 2
* Biological: Rabies mRNA vaccine CV7202 Dose level 3


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Subjects must satisfy the following criteria at trial entry: Healthy male and female subjects aged 18 to 40 years inclusive. Healthy Subject is defined as an individual who is in good general health, not having any mental or physical disorder requiring regular or frequent medication. Expected to be compliant with protocol procedures and available for clinical follow-up through the last planned visit. Physical examination and laboratory results without clinically significant findings. Body Mass Index (BMI) ≥18.0 and ≤32.0 kg/m2. Females: At the time of screening, negative human chorionic gonadotropin (hCG) pregnancy test (serum) for women presumed to be of childbearing potential on the day of enrolment. On Day 1 (pre-vaccination): negative urine pregnancy test (hCG), (only required if the screening visit serum pregnancy test was performed more than 3 days before). Females of childbearing potential must use acceptable methods of birth control from 2 weeks before the first administration of the test vaccine until 3 months following the last administration. Males must use reliable forms of contraception (condom) from the moment of the first administration of the test vaccine until 3 months following the last administration and must refrain from sperm donation from the moment of the first administration of the test vaccine until 3 months after the last administration. Exclusion Criteria Any trial subject who meets any of the following criteria will not qualify for entry into the trial Use of any investigational or non-registered product (drug or vaccine) other than the trial vaccine within 4 weeks preceding the administration of the trial vaccine, or planned use during the trial period. Receipt of any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrolment in this trial or planned receipt of any vaccine within 28 days of any trial vaccine administration. Receipt of any licensed or investigational rabies vaccine prior to the administration of the trial vaccine. Planning 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 during the trial and up to the end of the trial. Any treatment with immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the trial vaccine or planned use during the trial, with the exception of inhaled and nasal steroids, or topically-applied steroids. Any medically diagnosed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination, including human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection. History of a potential immune mediated disease. Administration of immunoglobulins (Igs) and/or any blood products within the 3 months preceding the administration of any dose of the trial vaccine. Presence or evidence of significant acute or chronic, uncontrolled medical or psychiatric illness. Known allergy to any component of CV7202 such as type I allergy to beta-lactam antibiotics or Rabipur®. Evidence of current alcohol or drug abuse. History of any neurological disorders or seizures including Guillain-Barré syndrome (GBS), with the exception of febrile seizures during childhood. Foreseeable non-compliance with protocol as judged by the investigator. For females: Pregnancy or lactation. History of any life-threatening anaphylactic reactions. Subjects with impaired coagulation or any bleeding disorder in whom an i.m. injection or a blood draw is contraindicated. Known relatives of site research staff working on this trial.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rabipur®<br> | Biological: Rabipur®<br>* 3 doses administered IM at Days 1, 8 and 29 in the deltoid region of the arm<br>* Other names: Licensed rabies vaccine containing inactivated rabies virus;|
| Experimental: CV7202 Dose level 1<br> | Biological: Rabies mRNA vaccine CV7202 Dose level 1<br>* 1 or 2 doses administered IM at Days 1 and 29 in the deltoid region of the arm<br>|
| Experimental: CV7202 Dose level 2<br> | Biological: Rabies mRNA vaccine CV7202 Dose level 2<br>* 1 or 2 doses administered IM at Days 1 and 29 in the deltoid region of the arm<br>|
| Experimental: CV7202 Dose level 3<br> | Biological: Rabies mRNA vaccine CV7202 Dose level 3<br>* 1 or 2 doses administered IM at Days 1 and 29 in the deltoid region of the arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary endpoint | The percentages of subjects with, and the frequencies and intensities of solicited local adverse events (AEs) | During a 8-day follow-up period (i.e.on the day of vaccination and 7 subsequent days) after each vaccination] | 
| Primary endpoint | The percentages of subjects with, and the frequencies, intensities and relationship to vaccination, of solicited systemic AEs | During a 8-day follow-up period (i.e., on the day of vaccination and 7 subsequent days) after each vaccination] | 
| Primary endpoint | The duration (in days) of solicited local AEs, of solicited systemic AEs and of the individual solicited AEs | During a 8-day follow-up period (i.e., on the day of vaccination and 7 subsequent days) after each vaccination] | 
| Primary endpoint | The percentages of subjects with and frequencies and intensities of any unsolicited and related unsolicited AEs | During a 29-day follow-up period (i.e., on the day of vaccination and 28 subsequent days) after each vaccination] | 
| Primary endpoint | The percentages of subjects with and frequencies and relationship to vaccination of any serious adverse events (SAEs) and any medically-attended AEs (MAAEs) | 0 - 12 months | 
| Primary endpoint | The percentages of subjects with and frequencies and relationship to vaccination of any adverse events of special interest (AESIs) | 0 - 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary endpoint | The percentages of subjects with and frequencies of SAEs and MAAEs related to study vaccination | 12 - 24 months | 
| Secondary endpoint | The percentages of subjects with and frequencies and relationship to vaccination of any AESIs | 12 - 24 months | 
| Secondary endpoint | Percentages of subjects with rabies-specific serum VNTs ≥0.5 IU/ml by trial Group. | 0-24 months | 
| Secondary endpoint | Serum geometric mean titers (GMTs) of virus-neutralizing antibodies by trial group | 0-24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rabies, Vaccine, Safety, Ractogenicity, Immunogenicity