CClinicalTrials.gg
CompletedNCT03713086Updated Dec 19, 2024Results posted

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

A Phase 1 interventional study of Rabipur® and Rabies mRNA vaccine CV7202 in Rabies, sponsored by CureVac. Completed at 2 sites in 2 countries. Open to participants aged 18 Years to 40 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-12-19.

Sponsored by CureVac · Phase 1, Interventional, and Prevention

Phase
Phase 1
Study type
Interventional
Enrollment
53
Allocation
Non-randomized
Ages
18 Years to 40 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Rabies

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Keywords

  • Rabies
  • Vaccine
  • Safety
  • Reactogenicity
  • Immunogenicity
03

Who can participate

Ages eligible
18 Years to 40 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

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.
04

Study design

Phase
Phase 1
Primary purpose
Prevention
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
53 participants (actual)

Study arms

  • Active comparator
    Rabipur®

    Participants received 3 doses of Rabipur® intramuscular injection at Days 1, 8 and 29 according to the manufacturer's recommendations.

    Biological: Rabipur®

  • Experimental
    CV7202 1 mcg

    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.

    Biological: Rabies mRNA vaccine CV7202

  • Experimental
    CV7202 2 mcg

    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.

    Biological: Rabies mRNA vaccine CV7202

  • Experimental
    CV7202 5 mcg

    Participants received mRNA CV7202 5 mcg intramuscular injection at Day 1.

    Biological: Rabies mRNA vaccine CV7202

Interventions

  • BiologicalRabipur®

    3 doses administered IM at Days 1, 8 and 29 in the deltoid region of the arm

    Also known as: Licensed rabies vaccine containing inactivated rabies virus

  • BiologicalRabies mRNA vaccine CV7202

    CV7202 administered IM at Days 1 and 29 in the deltoid region of the arm

  • BiologicalRabies mRNA vaccine CV7202

    CV7202 administered IM at Days 1 and 29 in the deltoid region of the arm

  • BiologicalRabies mRNA vaccine CV7202

    CV7202 administered IM at Days 1 and 29 in the deltoid region of the arm

05

What researchers measure

Primary outcomes

  1. Number of Participants Who Experienced a Local Solicited Adverse Event (AE) Post Dose 1 (Day 1)

    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.

    Time frame: From the first dose of vaccination up to 7 days after vaccination (up to Day 8)

  2. Number of Participants With Grade 0, 1, 2 and 3 Local Solicited AEs Post Dose 1 (Day 1)

    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).

    Time frame: From the first dose of vaccination up to 7 days after vaccination (up to Day 8)

  3. Number of Participants Who Experienced a Systemic Solicited AE and Related Systemic Solicited AE Post Dose 1 (Day 1)

    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.

    Time frame: From the first dose of vaccination up to 7 days after vaccination (up to Day 8)

  4. Number of Participants With Grade 0, 1, 2, and 3 of Systemic Solicited AEs and Related Systemic Solicited AEs Post Dose 1 (Day 1)

    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).

    Time frame: From the first dose of vaccination up to 7 days after vaccination (up to Day 8)

  5. Number of Days of Local Solicited AEs Post Dose 1 (Day 1)

    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.

    Time frame: From Day 1 (post-dose 1) to Day 8

  6. Number of Days of Local Solicited AEs Post Dose 2

    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.

    Time frame: CV7202: From Day 29 (post-dose 2) to Day 36; Rabipur: Day 8 (post-dose 2) to Day 15

  7. Number of Days of Local Solicited AEs Post Dose 3

    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.

    Time frame: Day 29 (post-dose 3) to Day 36

  8. Number of Days of Systemic Solicited AEs Post Dose 1

    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.

    Time frame: From Day 1 (post-dose 1) to Day 8

  9. Number of Days of Systemic Solicited AEs Post Dose 2

    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.

    Time frame: CV7202: From Day 29 (post-dose 2) to Day 36; Rabipur: Day 8 (post-dose 2) to Day 15

  10. Number of Days of Systemic Solicited AEs Post Dose 3

    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.

    Time frame: Day 29 (post-dose 3) to Day 36

  11. Number of Participants Who Experienced Unsolicited and Related Unsolicited AEs

    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.

    Time frame: From the first dose of vaccination up to 28 days after vaccination (up to Day 29)

  12. Number of Participants With Grade 1, 2 and 3 Unsolicited and Related Unsolicited AEs

    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.

    Time frame: From the first dose of vaccination up to 28 days after vaccination (up to Day 29)

  13. Number of Participants With Any Serious Adverse Events (SAEs) 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.

    Time frame: From the first dose of vaccination up to 12 months

  14. Number of Participants With Any Medically-attended AEs (MAAEs) 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.

    Time frame: From the first dose of vaccination up to 12 months

  15. Number of Participants With Any Adverse Events of Special Interest (AESIs) and Related AESI up to 12 Month

    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.

    Time frame: From the first dose of vaccination up to 12 months

Secondary outcomes

  1. Number of Participants With Related SAEs From 12 Months Post-vaccination 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.

    Time frame: From 12 months up to 24 months

  2. Number of Participants With Related MAAEs 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.

    Time frame: From 12 months up to 24 months

  3. Number of Participants With Any Related AESIs 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.

    Time frame: From 12 months up to 24 months

  4. Percentages of Participants With Rabies-specific Serum Virus-neutralizing Antibody Titer (VNTs)

    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.

    Time frame: Baseline (Day 1), Days 15, 43, 365, 547, and 730

  5. Serum Geometric Mean Titers (GMTs) of Rabies-specific VNTs

    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.

    Time frame: Baseline (Day 1), Days 8, 15, 29, 36, 43, 57, 91, 182, 365, 547, and 730

06

Results

Posted Dec 19, 2024

Participant flow

The study was conducted at 2 investigative sites in Germany and Belgium between 12 October 2018 and 23 November 2021.

Participant flow — Overall Study
MilestoneCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Started16161011
Received dose at day 116161011
Received dose at day 800011
Received dose at day 2988011
Completed1613910
Not completed0311
Withdrew: Withdrawal by subject0210
Withdrew: Lost to follow-up0101

Outcome measures

PrimaryNumber of Participants Who Experienced a Local Solicited Adverse Event (AE) Post Dose 1 (Day 1)

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.

Time frame:
From the first dose of vaccination up to 7 days after vaccination (up to Day 8)
Reported as:
Count of participants · Participants
Number of Participants Who Experienced a Local Solicited Adverse Event (AE) Post Dose 1 (Day 1)
ParticipantsCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Number of Participants Who Experienced a Local Solicited Adverse Event (AE) Post Dose 1 (Day 1)1315105
PrimaryNumber of Participants With Grade 0, 1, 2 and 3 Local Solicited AEs Post Dose 1 (Day 1)

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).

Time frame:
From the first dose of vaccination up to 7 days after vaccination (up to Day 8)
Reported as:
Count of participants · Participants
Number of Participants With Grade 0, 1, 2 and 3 Local Solicited AEs Post Dose 1 (Day 1)
ParticipantsCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Grade 0 (No AE/Absent)3105
Grade 1 (Mild)131345
Grade 2 (Moderate)0150
Grade 3 (Severe)0110
Not assessed0001
PrimaryNumber of Participants Who Experienced a Systemic Solicited AE and Related Systemic Solicited AE Post Dose 1 (Day 1)

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.

Time frame:
From the first dose of vaccination up to 7 days after vaccination (up to Day 8)
Reported as:
Count of participants · Participants
Number of Participants Who Experienced a Systemic Solicited AE and Related Systemic Solicited AE Post Dose 1 (Day 1)
ParticipantsCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Participants with Systemic Solicited AE111398
Participants with Related Systemic Solicited AE81395
PrimaryNumber of Participants With Grade 0, 1, 2, and 3 of Systemic Solicited AEs and Related Systemic Solicited AEs Post Dose 1 (Day 1)

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).

Time frame:
From the first dose of vaccination up to 7 days after vaccination (up to Day 8)
Reported as:
Count of participants · Participants
Number of Participants With Grade 0, 1, 2, and 3 of Systemic Solicited AEs and Related Systemic Solicited AEs Post Dose 1 (Day 1)
ParticipantsCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Participants with Systemic Solicited AEs — Grade 0 (No AE/Absent)5312
Participants with Systemic Solicited AEs — Grade 1 (Mild)8404
Participants with Systemic Solicited AEs — Grade 2 (Moderate)3634
Participants with Systemic Solicited AEs — Grade 3 (Severe)0360
Participants with Systemic Solicited AEs — Not assessed0001
Participants with Related Systemic Solicited AEs — Grade 0 (No AE/Absent)8315
Participants with Related Systemic Solicited AEs — Grade 1 (Mild)5402
Participants with Related Systemic Solicited AEs — Grade 2 (Moderate)3633
Participants with Related Systemic Solicited AEs — Grade 3 (Severe)0360
Participants with Related Systemic Solicited AEs — Not assessed0001
PrimaryNumber of Days of Local Solicited AEs Post Dose 1 (Day 1)

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.

Time frame:
From Day 1 (post-dose 1) to Day 8
Reported as:
Median · Days
Number of Days of Local Solicited AEs Post Dose 1 (Day 1)
DaysCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Pain1 (1 to 4)2 (1 to 3)3 (1 to 6)2 (1 to 4)
Redness——2 (2 to 2)—
PrimaryNumber of Days of Local Solicited AEs Post Dose 2

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.

Time frame:
CV7202: From Day 29 (post-dose 2) to Day 36; Rabipur: Day 8 (post-dose 2) to Day 15
Reported as:
Median · Days
Number of Days of Local Solicited AEs Post Dose 2
DaysCV7202 1 mcgCV7202 2 mcgRabipur®
Pain1 (1 to 4)2 (1 to 4)2 (1 to 4)
PrimaryNumber of Days of Local Solicited AEs Post Dose 3

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.

Time frame:
Day 29 (post-dose 3) to Day 36
Reported as:
Median · Days
Number of Days of Local Solicited AEs Post Dose 3
DaysRabipur®
Pain2 (1 to 2)
PrimaryNumber of Days of Systemic Solicited AEs Post Dose 1

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.

Time frame:
From Day 1 (post-dose 1) to Day 8
Reported as:
Median · Days
Number of Days of Systemic Solicited AEs Post Dose 1
DaysCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Temperature—1 (1 to 2)1 (1 to 1)—
Headache1 (1 to 4)2 (1 to 5)2 (1 to 4)1 (1 to 4)
Fatigue2 (1 to 2)2 (1 to 3)2 (1 to 7)1 (1 to 5)
Chills—1.5 (1 to 2)1 (1 to 2)—
Myalgia2 (1 to 5)3 (1 to 3)2 (1 to 5)1 (1 to 1)
Athralgia1 (1 to 3)1 (1 to 2)2 (1 to 3)—
Nausea/Vomiting1 (1 to 1)3 (3 to 3)1 (1 to 3)1 (1 to 1)
Diarrhea4 (4 to 4)1 (1 to 1)2 (1 to 3)—
PrimaryNumber of Days of Systemic Solicited AEs Post Dose 2

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.

Time frame:
CV7202: From Day 29 (post-dose 2) to Day 36; Rabipur: Day 8 (post-dose 2) to Day 15
Reported as:
Median · Days
Number of Days of Systemic Solicited AEs Post Dose 2
DaysCV7202 1 mcgCV7202 2 mcgRabipur®
Temperature1 (1 to 1)1.5 (1 to 2)—
Headache1 (1 to 3)2 (1 to 4)1.5 (1 to 2)
Fatigue2 (1 to 2)2 (2 to 3)2 (1 to 3)
Chills1.5 (1 to 2)1.5 (1 to 2)—
Myalgia1.5 (1 to 2)1.5 (1 to 2)—
Arthralgia1 (1 to 2)2 (2 to 2)—
Nausea/Vomiting—2 (2 to 2)—
Diarrhea—2 (2 to 2)—
PrimaryNumber of Days of Systemic Solicited AEs Post Dose 3

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.

Time frame:
Day 29 (post-dose 3) to Day 36
Reported as:
Median · Days
Number of Days of Systemic Solicited AEs Post Dose 3
DaysRabipur®
Headache1 (1 to 1)
Fatigue2 (2 to 2)
Chills1 (1 to 1)
PrimaryNumber of Participants Who Experienced Unsolicited and Related Unsolicited AEs

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.

Time frame:
From the first dose of vaccination up to 28 days after vaccination (up to Day 29)
Reported as:
Count of participants · Participants
Number of Participants Who Experienced Unsolicited and Related Unsolicited AEs
ParticipantsCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Participants with Unsolicited AEs101496
Participants with Related Unsolicited AEs2971
PrimaryNumber of Participants With Grade 1, 2 and 3 Unsolicited and Related Unsolicited AEs

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.

Time frame:
From the first dose of vaccination up to 28 days after vaccination (up to Day 29)
Reported as:
Count of participants · Participants
Number of Participants With Grade 1, 2 and 3 Unsolicited and Related Unsolicited AEs
ParticipantsCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Participants with all unsolicited AEs — Grade 1 (Mild)3322
Participants with all unsolicited AEs — Grade 2 (Moderate)4913
Participants with all unsolicited AEs — Grade 3 (Severe)3261
Participants with related unsolicited AEs — Grade 1 (Mild)1410
Participants with related unsolicited AEs — Grade 2 (Moderate)1311
Participants with related unsolicited AEs — Grade 3 (Severe)0250
PrimaryNumber of Participants With Any Serious Adverse Events (SAEs) 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.

Time frame:
From the first dose of vaccination up to 12 months
Reported as:
Count of participants · Participants
Number of Participants With Any Serious Adverse Events (SAEs) up to 12 Months
ParticipantsCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Number of Participants With Any Serious Adverse Events (SAEs) up to 12 Months1001
PrimaryNumber of Participants With Any Medically-attended AEs (MAAEs) 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.

Time frame:
From the first dose of vaccination up to 12 months
Reported as:
Count of participants · Participants
Number of Participants With Any Medically-attended AEs (MAAEs) up to 12 Months
ParticipantsCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Number of Participants With Any Medically-attended AEs (MAAEs) up to 12 Months6833
PrimaryNumber of Participants With Any Adverse Events of Special Interest (AESIs) and Related AESI up to 12 Month

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.

Time frame:
From the first dose of vaccination up to 12 months
Reported as:
Count of participants · Participants
Number of Participants With Any Adverse Events of Special Interest (AESIs) and Related AESI up to 12 Month
ParticipantsCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Participants with AESIs0000
Participants with related AESIs0000
SecondaryNumber of Participants With Related SAEs From 12 Months Post-vaccination 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.

Time frame:
From 12 months up to 24 months
Reported as:
Count of participants · Participants
Number of Participants With Related SAEs From 12 Months Post-vaccination up to 24 Months
ParticipantsCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Number of Participants With Related SAEs From 12 Months Post-vaccination up to 24 Months0000
SecondaryNumber of Participants With Related MAAEs 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.

Time frame:
From 12 months up to 24 months
Reported as:
Count of participants · Participants
Number of Participants With Related MAAEs From 12 Months up to 24 Months
ParticipantsCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Number of Participants With Related MAAEs From 12 Months up to 24 Months0000
SecondaryNumber of Participants With Any Related AESIs 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.

Time frame:
From 12 months up to 24 months
Reported as:
Count of participants · Participants
Number of Participants With Any Related AESIs From 12 Months up to 24 Months
ParticipantsCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Number of Participants With Any Related AESIs From 12 Months up to 24 Months0010
SecondaryPercentages of Participants With Rabies-specific Serum Virus-neutralizing Antibody Titer (VNTs)

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.

Time frame:
Baseline (Day 1), Days 15, 43, 365, 547, and 730
Reported as:
Number · percentage of participants
Percentages of Participants With Rabies-specific Serum Virus-neutralizing Antibody Titer (VNTs)
percentage of participantsCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Baseline (Day 1)0.0 (0.0 to 20.6)0.0 (0.0 to 20.6)0.0 (0.0 to 30.8)0.0 (0.0 to 30.8)
Day 150.0 (0.0 to 20.6)6.3 (0.2 to 30.2)0.0 (0.0 to 30.8)100.0 (69.2 to 100.0)
Day 4350.0 (24.7 to 75.3)62.5 (35.4 to 84.8)22.2 (2.8 to 60.0)100.0 (69.2 to 100.0)
Day 36512.5 (1.6 to 38.3)14.3 (1.8 to 42.8)11.1 (0.3 to 48.2)100.0 (69.2 to 100.0)
Day 54722.2 (2.8 to 60.0)28.6 (3.7 to 71.0)16.7 (0.4 to 64.1)90.0 (55.5 to 99.7)
Day 73022.2 (2.8 to 60.0)42.9 (9.9 to 81.6)16.7 (0.4 to 64.1)90.0 (55.5 to 99.7)
SecondarySerum Geometric Mean Titers (GMTs) of Rabies-specific VNTs

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.

Time frame:
Baseline (Day 1), Days 8, 15, 29, 36, 43, 57, 91, 182, 365, 547, and 730
Reported as:
Geometric mean · IU/mL
Serum Geometric Mean Titers (GMTs) of Rabies-specific VNTs
IU/mLCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
Baseline (Day 1)0.050 ± 1.00000.050 ± 1.00000.050 ± 1.00000.050 ± 1.0000
Day 80.053 ± 1.26980.053 ± 1.21790.050 ± 1.00000.057 ± 1.3394
Day 150.069 ± 1.88030.095 ± 2.67020.062 ± 1.56857.834 ± 2.7369
Day 290.092 ± 1.98640.189 ± 3.86040.144 ± 2.80644.478 ± 3.0074
Day 360.231 ± 3.29580.433 ± 5.17840.136 ± 3.10088.921 ± 2.4253
Day 430.653 ± 9.38710.692 ± 8.36400.122 ± 2.97909.341 ± 2.2222
Day 570.540 ± 8.27280.502 ± 7.68460.125 ± 2.87867.849 ± 1.8818
Day 910.445 ± 5.85680.275 ± 6.04280.105 ± 2.91334.888 ± 1.8755
Day 1820.176 ± 4.64980.163 ± 3.61990.074 ± 2.44211.089 ± 1.9244
Day 3650.095 ± 2.75110.097 ± 2.88420.072 ± 2.34570.816 ± 2.1405
Day 5470.132 ± 2.74280.149 ± 3.63180.077 ± 2.91980.879 ± 1.9594
Day 7300.128 ± 3.92130.246 ± 4.09630.073 ± 2.56000.831 ± 2.0624

Adverse events

Collected over From the first dose of vaccination up to 24 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
CV7202 1 mcg0/16 (0%)1/16 (6.3%)14/16 (87.5%)
CV7202 2 mcg0/16 (0%)0/16 (0%)14/16 (87.5%)
CV7202 5 mcg0/10 (0%)0/10 (0%)10/10 (100%)
Rabipur®0/11 (0%)1/11 (9.1%)8/11 (72.7%)
Most frequent serious events
Most frequent serious events
EventCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
AppendicitisInfections and infestations0/160/160/101/11
Herpes zosterInfections and infestations1/160/160/100/11
Most frequent other events
Showing 10 of 104
Most frequent other events
EventCV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®
HeadacheNervous system disorders4/161/168/102/11
NasopharyngitisInfections and infestations9/165/167/104/11
ArthralgiaMusculoskeletal and connective tissue disorders0/161/163/101/11
PyrexiaGeneral disorders2/161/163/100/11
Night sweatsSkin and subcutaneous tissue disorders0/160/163/100/11
Decreased appetiteMetabolism and nutrition disorders0/160/163/100/11
Upper respiratory tract infectionInfections and infestations0/164/161/100/11
TonsillitisInfections and infestations0/160/162/100/11
DizzinessNervous system disorders0/161/162/101/11
Abdominal painGastrointestinal disorders0/160/162/100/11

Baseline characteristics

Safety analysis set included all participants who had received at least 1 dose of mRNA vaccine CV7202 or Rabipur and those participants who had any post-Day 1 safety data.

Age, Continuous
Age, Continuous(years)CV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®Total
Mean27.1 ± 5.6228.3 ± 5.8126.1 ± 3.9625.5 ± 4.2326.9 ± 5.11
Sex: Female, Male
Sex: Female, Male(Participants)CV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®Total
Female9125733
Male745420
Race (NIH/OMB)
Race (NIH/OMB)(Participants)CV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®Total
American Indian or Alaska Native00000
Asian00000
Native Hawaiian or Other Pacific Islander00000
Black or African American00000
White1516101152
More than one race00000
Unknown or Not Reported10001
Region of Enrollment
Region of Enrollment(participants)CV7202 1 mcgCV7202 2 mcgCV7202 5 mcgRabipur®Total
Belgium168101145
Germany08008
07

Study locations

2 sites
  • University Hospital Ghent
    Ghent, 9000, Belgium
  • Department of Infectious Diseases and Tropical Medicine (DITM), Medical Center of the University of Munich
    Munich, Bavaria 80802, Germany
08

References and documents

Publications

  • 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. PubMed 33487468 ↗

Study documents

  • Study protocol · Apr 30, 2020
  • Statistical analysis plan · Feb 24, 2022

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03713086
Lead sponsor
CureVac
Responsible party
Sponsor
First posted
Oct 19, 2018
Start date
Oct 12, 2018
Primary completion
Nov 23, 2021
Completion
Nov 23, 2021
Results posted
Dec 19, 2024
Last update
Dec 19, 2024

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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