A Study to Assess the Safety, Reactogenicity and Immune Response of CureVac's Candidate Rabies mRNA Vaccine in Healthy Adults
- Conditions
- Rabies
- Interventions
- Biological: Rabipur®Biological: Rabies mRNA vaccine CV7202
- Registration Number
- NCT03713086
- Lead Sponsor
- CureVac
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 53
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Rabipur® Rabipur® Participants received 3 doses of Rabipur® intramuscular injection at Days 1, 8 and 29 according to the manufacturer's recommendations. CV7202 1 mcg Rabies mRNA vaccine CV7202 Participants received messenger ribonucleic acid (mRNA) CV7202 1 microgram (mcg) intramuscular injection at Day 1, of whom half of the participants received a second dose of CV7202 1 mcg at Day 29. CV7202 2 mcg Rabies mRNA vaccine CV7202 Participants received mRNA CV7202 2 mcg intramuscular injection at Day 1, of whom half of the participants received a second dose of CV7202 2 mcg at Day 29. CV7202 5 mcg Rabies mRNA vaccine CV7202 Participants received mRNA CV7202 5 mcg intramuscular injection at Day 1.
- Primary Outcome Measures
Name Time Method Number of Participants Who Experienced a Local Solicited Adverse Event (AE) Post Dose 1 (Day 1) From the first dose of vaccination up to 7 days after vaccination (up to Day 8) An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. Local solicited AEs included injection site pain, redness, swelling, and itching. All AEs were documented in a diary by the participant.
Number of Participants With Grade 0, 1, 2 and 3 Local Solicited AEs Post Dose 1 (Day 1) From the first dose of vaccination up to 7 days after vaccination (up to Day 8) An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. The intensity of local solicited AEs was graded as:Pain at injection site(Grade 0:absent,Grade 1:Does not interfere with activity, Grade 2:Interferes with activity/repeated use of non-narcotic pain reliever greater than \[\>\] 24 hours,Grade 3:prevent daily activity/repeated use of narcotic pain reliever); Redness(Grade 0:less than or equal to \[\<=\]2.5 centimeters(cm), Grade 1:2.5 to 5cm,Grade 2: 5.1 to 10cm, Grade 3: \>10cm);Swelling(Grade 0: \<=2.5 cm,Grade 1: 2.5 to 5cm and does not interfere with activity,Grade 2:5.1 to 10cm/interferes with activity,Grade 3:\>10cm or prevents daily activity);Itching(Grade 0:absent,Grade 1:Mild,no interference with normal activity,Grade 2:Moderate,some interference with normal activity,Grade 3:Significant, prevents normal activity).
Number of Participants Who Experienced a Systemic Solicited AE and Related Systemic Solicited AE Post Dose 1 (Day 1) From the first dose of vaccination up to 7 days after vaccination (up to Day 8) An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. Systemic solicited AEs included fever, nausea/vomiting, diarrhea, headache, fatigue, myalgia, and arthralgia on the day of vaccination and following 7 days after dose 1. All AEs were documented in diary by the participant.
Number of Participants With Grade 0, 1, 2, and 3 of Systemic Solicited AEs and Related Systemic Solicited AEs Post Dose 1 (Day 1) From the first dose of vaccination up to 7 days after vaccination (up to Day 8) The intensity of Systemic AEs was graded as: Fever(Grade 0: \<38 degree Celsius (°C), Grade 1: \>=38°C to 38.4°C, Grade 2:\>=38.5°C to 38.9°C, Grade 3: \>=39°C); Headache(Grade 0: absent, Grade 1: Mild, Grade 2: Moderate, Grade 3: Significant); Fatigue(Grade 0: Absent, Grade 1: Mild, Grade 2: Moderate, Grade 3: Significant); Chills(Grade 0: Absent, Grade 1: Mild, Grade 2: Moderate, Grade 3: Significant); Myalgia(Grade 0: Absent, Grade 1: Mild, Grade 2: Moderate, Grade 3: Significant); Arthralgia(Grade 0: Absent, Grade 1: Mild, Grade 2: Moderate, Grade 3: Significant); Nausea/Vomiting(Grade 0: Absent, Grade 1: Mild, no interference with activity/1-2 episodes/24 hours, Grade 2: Moderate, some interference with activity/\>2 episodes/ 24 hours, Grade 3: Severe, prevents daily activity, requires outpatient intravenous \[IV\] hydration); Diarrhea(Grade 0: Absent, Grade 1: 2-3 stools, Grade 2: 4-5 stools, Grade 3: 6 or more watery stools or requires outpatient IV hydration).
Number of Days of Local Solicited AEs Post Dose 1 (Day 1) From Day 1 (post-dose 1) to Day 8 An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. Local solicited AEs included injection site pain, redness, swelling, and itching. All AEs were documented in diary by the participant.
Number of Days of Local Solicited AEs Post Dose 2 CV7202: From Day 29 (post-dose 2) to Day 36; Rabipur: Day 8 (post-dose 2) to Day 15 An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. Local solicited AEs included injection site pain, redness, swelling, and itching. All AEs were documented in diary by the participant.
Number of Days of Local Solicited AEs Post Dose 3 Day 29 (post-dose 3) to Day 36 An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. Local solicited AEs included injection site pain, redness, swelling, and itching. All AEs were documented in diary by the participant.
Number of Days of Systemic Solicited AEs Post Dose 1 From Day 1 (post-dose 1) to Day 8 An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. Systemic solicited AEs included fever, nausea/vomiting, chills, diarrhea, headache, fatigue, myalgia, and arthralgia. All AEs were documented in diary by the participant.
Number of Days of Systemic Solicited AEs Post Dose 2 CV7202: From Day 29 (post-dose 2) to Day 36; Rabipur: Day 8 (post-dose 2) to Day 15 An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. Systemic solicited AEs included fever, nausea/vomiting, diarrhea, chills, headache, fatigue, myalgia, and arthralgia. All AEs were documented in diary by the participant.
Number of Days of Systemic Solicited AEs Post Dose 3 Day 29 (post-dose 3) to Day 36 An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. Systemic solicited AEs included fever, nausea/vomiting, diarrhea, headache, fatigue, myalgia, and arthralgia. All AEs were documented in diary by the participant.
Number of Participants Who Experienced Unsolicited and Related Unsolicited AEs From the first dose of vaccination up to 28 days after vaccination (up to Day 29) An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. An unsolicited AE was defined as any other AE reported by the participant via diary cards or during study visits on the day of vaccination and the 28 subsequent days. The number of participants with unsolicited and related unsolicited AEs were reported.
Number of Participants With Grade 1, 2 and 3 Unsolicited and Related Unsolicited AEs From the first dose of vaccination up to 28 days after vaccination (up to Day 29) An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. An unsolicited AE was defined as any other AE reported by the participant via diary cards or during study visits on the day of vaccination and the 28 subsequent days. The intensity of AEs was graded as: 1) Mild (Grade 1): An event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities.; 2) Moderate (Grade 2): An event that caused sufficient discomfort to interfere with normal everyday activities.; 3) Severe (Grade 3): An event that prevented normal everyday activities. Number of participants with Grade 1, 2 and 3 unsolicited and related unsolicited AEs were reported.
Number of Participants With Any Serious Adverse Events (SAEs) up to 12 Months From the first dose of vaccination up to 12 months An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. SAE was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect.
Number of Participants With Any Medically-attended AEs (MAAEs) up to 12 Months From the first dose of vaccination up to 12 months An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. Vaccine-related MAAEs include any AEs for which the participant received medical attention, defined as hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel for any reason for which there is evidence to suggest a causal relationship between the study product and the adverse event. Number of participants with any MAAEs were reported.
Number of Participants With Any Adverse Events of Special Interest (AESIs) and Related AESI up to 12 Month From the first dose of vaccination up to 12 months An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. AEs with a suspected potential immune-mediated disease etiology was considered as AESIs. AESI was assessed by the investigator. Vaccine-related AESIs was included as AESIs for which there was evidence to suggest a causal relationship between the study product and the adverse event.
- Secondary Outcome Measures
Name Time Method Number of Participants With Related SAEs From 12 Months Post-vaccination up to 24 Months From 12 months up to 24 months An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. SAE was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. Vaccine-related SAEs was included as SAEs for which there is evidence to suggest a causal relationship between the study product and the adverse event.
Number of Participants With Related MAAEs From 12 Months up to 24 Months From 12 months up to 24 months An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. Vaccine-related MAAEs include any AEs for which the participant received medical attention, defined as hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel for any reason for which there is evidence to suggest a causal relationship between the study product and the adverse event. Number of participants with related MAAEs were reported.
Number of Participants With Any Related AESIs From 12 Months up to 24 Months From 12 months up to 24 months An AE was defined as any untoward medical occurrence in a clinical study participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. AEs with a suspected potential immune-mediated disease etiology was considered as AESIs. AESI was assessed by the investigator. Vaccine-related AESIs was included as AESIs for which there was evidence to suggest a causal relationship between the study product and the adverse event. Number of participants with any related AESIs were reported.
Percentages of Participants With Rabies-specific Serum Virus-neutralizing Antibody Titer (VNTs) Baseline (Day 1), Days 15, 43, 365, 547, and 730 Rabies-specific serum response was defined as VNT ≥ 0.5 international units per milliliter (IU/mL). Rabies-specific serum VNT were measured using the WHO-recommended rapid fluorescent foci inhibition test (RFFIT). Serial dilutions of each serum sample are mixed with a standard dose of rabies virus before tissue culture cells are added. Virus infected cells are detected via a fluorochrome conjugated rabies-specific antibody. If the serum contains antibodies that bind and neutralize the virus, the infectivity of the virus is reduced. The virus neutralization end-point titer is defined as the highest sample dilution at which 50% of the observed microscopic fields contain ≥ 1 infected cell. The percentages of participants with rabies-specific serum VNTs ≥0.5 were taken as positive and were reported.
Serum Geometric Mean Titers (GMTs) of Rabies-specific VNTs Baseline (Day 1), Days 8, 15, 29, 36, 43, 57, 91, 182, 365, 547, and 730 Serum geometric mean titer (antilog mean of log-transformed VNTs) was obtained from measuring VNTs using the WHO-recommended rapid fluorescent foci inhibition test. The virus neutralization end-point titer (VNT) is defined as the highest sample dilution at which 50% of the observed microscopic fields contain \>=1 infected cell.
Trial Locations
- Locations (2)
Department of Infectious Diseases and Tropical Medicine (DITM), Medical Center of the University of Munich
🇩🇪Munich, Bavaria, Germany
University Hospital Ghent
🇧🇪Ghent, Belgium