Clinical trial NCT02241135: RNActive® Rabies Vaccine (CV7201) in Healthy Adults
Official title: Phase I Safety and Immunogenicity Trial of an Investigational RNActive® Rabies Vaccine (CV7201) in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rabies
Keywords: Rav G protein
rabies
VNT
immunogenicity
PrEP vaccination
mRNA
CV7201
Lead sponsor: CureVac
Sponsor class: INDUSTRY
First posted: 2014-09-16
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this trial is to assess the safety and immunogenicity of an investigational RNActive® rabies vaccine (CV7201) in healthy adults.


Eligibility criteria: Inclusion Criteria:

1. Healthy male and female volunteers aged 18 to 40 years inclusive
2. Compliant with protocol procedures and available for clinical follow-up through the last planned visit (V9)
3. Physical examination and laboratory results without clinically significant findings
4. Body Mass Index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2
5. Females: Negative human chorionic gonadotropin (HCG) pregnancy test (serum) for women presumed to be of reproductive potential on the day of enrolment
6. Females of childbearing potential must use acceptable methods of birth control during the trial and Follow-up period (from 6 weeks before the first administration of the test vaccine for the duration of the trial i.e., until the last planned visit (V9)). The following methods of birth control are acceptable when used consistently and correctly: established use of oral, injected or implanted hormonal methods of contraception; intrauterine devices (IUDs) or intrauterine systems (IUSs) with the exception of steel or copper wire; barrier methods of contraception (condom or occlusive cap \[diaphragm or cervical/vault caps\] with spermicidal foam/gel/film/cream/suppository); true abstinence (periodic abstinence \[e.g., calendar, ovulation, symptothermal and postovulation methods\] and withdrawal are not acceptable).
7. Males must use reliable forms of contraception (barrier method with spermicidal agent or true abstinence) and must refrain from sperm donation during the trial and Follow-up period i.e., until the last planned visit (V9).

Exclusion Criteria:

1. 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
2. Subject has received any other licensed vaccines within 4 weeks prior to the administration of the trial vaccine
3. Subject has received any investigational or licensed rabies vaccine previously
4. Intending to travel to regions/countries for which rabies vaccinations are recommended or where high risk of infections exists according to travel recommendations by the German Society of Tropical Medicine and International Health (DTG) during the trial and up to V9 (Day 91/120) Follow-up
5. Any treatment with immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the trial vaccine. The use of inhaled and nasal steroids, as well as topical steroids outside the vaccination area, will be permitted
6. Any medically diagnosed or suspected immunodeficient condition based on medical history and physical examination
7. History of autoimmune disease
8. Administration of immunoglobulins (Igs) and/or any blood products within the 3 months preceding the administration of the trial vaccine
9. Subject is taking chloroquine for malaria treatment or prophylaxis
10. Acute disease at the time of enrolment. Acute disease is defined as the presence of a moderate or severe illness or fever ≥ 38 °C measured orally
11. Presence or evidence of significant acute or chronic, 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
12. Major congenital defects
13. Known allergy to any component of the trial product i.e., protamine. This includes subjects with allergy to fish protein, diabetics with allergy to protamine-containing insulin, or post-vasectomy males
14. Known type I allergy to beta lactam antibiotics
15. Evidence of current alcohol or drug abuse
16. History of any neurological disorders or seizures, with the exception of febrile seizures during childhood
17. Seropositivity for human immunodeficiency virus (HIV), hepatitis B virus (HBV) (except in subjects previously vaccinated against HBV) or hepatitis C virus (HCV)
18. Foreseeable non-compliance with protocol as judged by the Investigator
19. For females: Pregnancy or lactation
20. History of any life-threatening anaphylactic reactions.
21. Subjects with impaired coagulation in whom an IM injection is contraindicated.

Primary outcomes:
measure: Incidence and severity of serious adverse events (SAEs)/adverse events (AEs) and local tolerability assessment of the vaccination site
timeFrame: up to 64 days after the last vaccination
Secondary outcomes:
measure: The lowest CV7201 dose to elicit rabies VNTs ≥ 0.5 IE/ml
timeFrame: Rabies VNTs measured 14 days after the 3rd vaccination (Visit 8)
measure: Number of treatment discontinuation due to IMP-related AEs/SAEs
timeFrame: up to 64 days after the last vaccination
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Abteilung für Infektions- und Tropenmedizin der Ludwig-Maximilians-Universität
Study officials:
affiliation: Ludwig-Maximilians - University of Munich
name: Franz-Josef Falkner von Sonnenburg, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alberer M, Gnad-Vogt U, Hong HS, Mehr KT, Backert L, Finak G, Gottardo R, Bica MA, Garofano A, Koch SD, Fotin-Mleczek M, Hoerr I, Clemens R, von Sonnenburg F. Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial. Lancet. 2017 Sep 23;390(10101):1511-1520. doi: 10.1016/S0140-6736(17)31665-3. Epub 2017 Jul 25.