Clinical trial NCT03713086: A Study to Assess the Safety, Reactogenicity and Immune Response of CureVac's Candidate Rabies mRNA Vaccine in Healthy Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rabies
Keywords: Rabies
Vaccine
Safety
Reactogenicity
Immunogenicity
Lead sponsor: CureVac
Sponsor class: INDUSTRY
First posted: 2018-10-19
Enrollment: 53
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 primary objective of this clinical study is to assess the safety, and reactogenicity of CV7202 mRNA-rabies vaccine in healthy adults. Immunogenicity is also assessed.


Eligibility criteria: Inclusion criteria: Subjects must satisfy the following criteria at trial entry:

1. 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.
2. Expected to be compliant with protocol procedures and available for clinical follow-up through the last planned visit.
3. Physical examination and laboratory results without clinically significant findings.
4. Body Mass Index (BMI) ≥18.0 and ≤32.0 kg/m2.
5. 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).
6. 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.
7. 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

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. 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.
3. Receipt of any licensed or investigational rabies vaccine prior to the administration of the trial vaccine.
4. 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.
5. 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.
6. 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.
7. History of a potential immune mediated disease.
8. Administration of immunoglobulins (Igs) and/or any blood products within the 3 months preceding the administration of any dose of the trial vaccine.
9. Presence or evidence of significant acute or chronic, uncontrolled medical or psychiatric illness.
10. Known allergy to any component of CV7202 such as type I allergy to beta-lactam antibiotics or Rabipur®.
11. Evidence of current alcohol or drug abuse.
12. History of any neurological disorders or seizures including Guillain-Barré syndrome (GBS), with the exception of febrile seizures during childhood.
13. Foreseeable non-compliance with protocol as judged by the investigator.
14. For females: Pregnancy or lactation.
15. History of any life-threatening anaphylactic reactions.
16. Subjects with impaired coagulation or any bleeding disorder in whom an i.m. injection or a blood draw is contraindicated.
17. Known relatives of site research staff working on this trial.

Primary outcomes:
measure: Number of Participants Who Experienced a Local Solicited Adverse Event (AE) Post Dose 1 (Day 1)
timeFrame: From the first dose of vaccination up to 7 days after vaccination (up to Day 8)
measure: Number of Participants With Grade 0, 1, 2 and 3 Local Solicited AEs Post Dose 1 (Day 1)
timeFrame: From the first dose of vaccination up to 7 days after vaccination (up to Day 8)
measure: Number of Participants Who Experienced a Systemic Solicited AE and Related Systemic Solicited AE Post Dose 1 (Day 1)
timeFrame: From the first dose of vaccination up to 7 days after vaccination (up to Day 8)
measure: Number of Participants With Grade 0, 1, 2, and 3 of Systemic Solicited AEs and Related Systemic Solicited AEs Post Dose 1 (Day 1)
timeFrame: From the first dose of vaccination up to 7 days after vaccination (up to Day 8)
measure: Number of Days of Local Solicited AEs Post Dose 1 (Day 1)
timeFrame: From Day 1 (post-dose 1) to Day 8
measure: Number of Days of Local Solicited AEs Post Dose 2
timeFrame: CV7202: From Day 29 (post-dose 2) to Day 36; Rabipur: Day 8 (post-dose 2) to Day 15
measure: Number of Days of Local Solicited AEs Post Dose 3
timeFrame: Day 29 (post-dose 3) to Day 36
measure: Number of Days of Systemic Solicited AEs Post Dose 1
timeFrame: From Day 1 (post-dose 1) to Day 8
measure: Number of Days of Systemic Solicited AEs Post Dose 2
timeFrame: CV7202: From Day 29 (post-dose 2) to Day 36; Rabipur: Day 8 (post-dose 2) to Day 15
measure: Number of Days of Systemic Solicited AEs Post Dose 3
timeFrame: Day 29 (post-dose 3) to Day 36
measure: Number of Participants Who Experienced Unsolicited and Related Unsolicited AEs
timeFrame: From the first dose of vaccination up to 28 days after vaccination (up to Day 29)
measure: Number of Participants With Grade 1, 2 and 3 Unsolicited and Related Unsolicited AEs
timeFrame: From the first dose of vaccination up to 28 days after vaccination (up to Day 29)
measure: Number of Participants With Any Serious Adverse Events (SAEs) up to 12 Months
timeFrame: From the first dose of vaccination up to 12 months
measure: Number of Participants With Any Medically-attended AEs (MAAEs) up to 12 Months
timeFrame: From the first dose of vaccination up to 12 months
measure: Number of Participants With Any Adverse Events of Special Interest (AESIs) and Related AESI up to 12 Month
timeFrame: From the first dose of vaccination up to 12 months
Secondary outcomes:
measure: Number of Participants With Related SAEs From 12 Months Post-vaccination up to 24 Months
timeFrame: From 12 months up to 24 months
measure: Number of Participants With Related MAAEs From 12 Months up to 24 Months
timeFrame: From 12 months up to 24 months
measure: Number of Participants With Any Related AESIs From 12 Months up to 24 Months
timeFrame: From 12 months up to 24 months
measure: Percentages of Participants With Rabies-specific Serum Virus-neutralizing Antibody Titer (VNTs)
timeFrame: Baseline (Day 1), Days 15, 43, 365, 547, and 730
measure: Serum Geometric Mean Titers (GMTs) of Rabies-specific VNTs
timeFrame: Baseline (Day 1), Days 8, 15, 29, 36, 43, 57, 91, 182, 365, 547, and 730
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Munich
country: Germany
facility: Department of Infectious Diseases and Tropical Medicine (DITM), Medical Center of the University of Munich
state: Bavaria
Study officials:
References:
citation: Aldrich C, Leroux-Roels I, Huang KB, Bica MA, Loeliger E, Schoenborn-Kellenberger O, Walz L, Leroux-Roels G, von Sonnenburg F, Oostvogels L. Proof-of-concept of a low-dose unmodified mRNA-based rabies vaccine formulated with lipid nanoparticles in human volunteers: A phase 1 trial. Vaccine. 2021 Feb 22;39(8):1310-1318. doi: 10.1016/j.vaccine.2020.12.070. Epub 2021 Jan 22.