None listed
Conditions
Interventions
The objective of Phase 2b is to further characterize the safety, reactogenicity, and immunogenicity of CVnCoV prior to initiating Phase 3. CVnCoV will be administered at the 12 µg dose level selected for Phase 3 investigation informed by the safety and immunogenicity data from the initial Phase 1 and 2a trials. Phase 2b will be conducted in 2 age groups of adults: 18 to 60 and ≥
61 years of age, which represent the age range of the intended Phase 3 trial population.
Approximately 4,000 subjects will be enrolled and randomized in a 1:1 ratio to receive 2 doses of either CV
This group in the corresponding control of the experimental mentioned above, for participants of phase 3. The control treatment consist of the same volume of 0.9% saline, administered on days 1 and 29. 2 doses, on days 1 and 29.
Sponsors
CureVac AG,
Eligibility
Inclusion criteria
Inclusion criteria: 1. Male or female subjects 18 years of age or older. 2. Provide written informed consent prior to initiation of any trial procedures. 3. Expected compliance with protocol procedures and availability for clinical follow-up through the last planned visit. 4. Females of non-childbearing potential defined as follows: surgically sterile (history of bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or postmenopausal {defined as amenorrhea for ≥ 12 consecutive months prior to screening (Day 1)} without an alternative medical cause). A follicle-stimulating hormone (FSH) level may be measured at the discretion of the Investigator to confirm postmenopausal status. 5. Females of childbearing potential: negative urine pregnancy test {human chorionic gonadotropin (hCG)} within 24 hours prior to each trial vaccination on Day 1 and Day 29. 6. Females of childbearing potential must use highly effective methods of birth control from 2 weeks before the first administration of the trial vaccine until 3 months following the last administration. The following methods of birth control are considered highly effective when used consistently and correctly: · Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal); · Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable); · Intrauterine devices (IUDs); · Intrauterine hormone-releasing systems (IUSs); · Bilateral tubal occlusion; · Vasectomized or infertile partner; · Sexual abstinence {periodic abstinence (e.g., calendar, ovulation, symptothermal and post-ovulation methods) and withdrawal are not acceptable}.
Exclusion criteria
Exclusion criteria: 1. History of virologically-confirmed COVID-19 illness. 2. For females: pregnancy or lactation. 3. Use of any investigational or non-registered product (vaccine or drug) within 28 days preceding the administration of the first trial vaccine or planned use during the trial. 4. Receipt of licensed vaccines within 28 days (for live vaccines) or 14 days (for inactivated vaccines) prior to the administration of the first trial vaccine. 5. Prior administration of any investigational SARS-CoV-2 vaccine or another coronavirus (SARS-CoV, MERS-CoV) vaccine or planned use during the trial. 6. Any treatment with immunosuppressants or other immune-modifying drugs (including but not limited to corticosteroids, biologicals and methotrexate) for > 14 days total within 6 months preceding the administration of trial vaccine or planned use during the trial. For corticosteroid use, this means prednisone or equivalent, 0.5 mg/kg/day for 14 days or more. The use of inhaled, topical, or localized injections of corticosteroids (e.g., for joint pain/inflammation) is permitted. 7. Any medically diagnosed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination including known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); current diagnosis of or treatment for cancer including leukemia, lymphoma, Hodgkin disease, multiple myeloma, or generalized malignancy; chronic renal failure or nephrotic syndrome; and receipt of an organ or bone marrow transplant. 8. History of angioedema (hereditary or idiopathic), or history of any anaphylactic reaction and pIMD. 9. History of allergy to any component of CVnCoV vaccine. 10. Administration of immunoglobulins or any blood products within 3 months prior to the administration of trial vaccine or planned receipt during the trial. 11. Subjects with a significant acute or chronic medical or psychiatric illness that, in the opinion of the Investigator, precludes trial participation (e.g., may increase the risk of trial participation, render the subject unable to meet the requirements of the trial, or may interfere with the subject’s trial evaluations). These include severe and/or uncontrolled cardiovascular disease, gastrointestinal disease, liver disease, renal disease, respiratory disease, endocrine disorder, and neurological and psychiatric illnesses. However, those with controlled and stable cases can be included in the trial. 12. Subjects with impaired coagulation or any bleeding disorder in whom an intramuscular injection or a blood draw is contraindicated. 13. Foreseeable non-compliance with the trial procedures as judged by the Investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Outcome name:In primary efficacy analysis, the VE, defined as the percent reduction in the frequency of any and moderate to severe COVID-19 cases (according to primary case definitions) in vaccinated subjects compared with subjects who received placebo will be calculated with exact 95%* CI as follows: VE = 1- RR = 1 - (ARV/ARP) = 1 - {p / r (1-p)} where ARV = attack rate in vaccinated group = nv/Nv = number of subjects reporting at least one COVID-19 episode in the CVnCoV group / total follow-up time of evaluable subjects in the CVnCoV group (number of person-month). ARP = attack rate in placebo group = np/Np = number of subjects reporting at least one COVID-19 episode in the placebo group / total follow-up time of evaluable subjects in the placebo group (number of person-month). RR = relative risk = ARV/ARP p = proportion of COVID-19 cases (according to primary case definition) coming from the CVnCoV group among all cases = nv/(nv+np). r = ratio of total follow-up time of evaluable subjects in the CVnCoV group over total follow-up time of evaluable subjects in the placebo group = Nv/Np. *Level of CI may be slightly adjusted due to the sequential design Measure:Co-Primary Efficacy Endpoints · Occurrence of first episodes of virologically-confirmed (RT-PCR positive) cases of COVID-19 of any severity meeting the case definition for the primary efficacy analysis. · Occurrence of first episodes of virologically-confirmed (RT-PCR positive) cases of moderate to severe COVID-19 meeting the case definition for the primary efficacy analysis (moderate and severe COVID-19 disease is defined in Appendix 3 and Appendix 4). Primary Safety Endpoints · Occurrence, intensity and relationship of medically-attended AEs collected through 6 months after the second trial vaccination in all subjects. · Occurrence, intensity and relationship of SAEs and AESIs collected through 1 year after the second trial vaccination in all subjects. | — |
Secondary
| Measure | Time frame |
|---|---|
| Outcome name:Statistical testing of the 2 key secondary efficacy endpoints will be performed according to the conditional hierarchical testing procedure using the order defined in the objective/endpoints sections. Consequently: · Efficacy of CVnCoV in regard to severe cases will be demonstrated only if there is successful demonstration of the primary efficacy objective. · Efficacy of CVnCoV in regard to asymptomatic infection will be demonstrated only if there is successful demonstration of the primary efficacy objective and secondary objective on severe cases. Otherwise, these endpoints will be analyzed as exploratory endpoints without success criteria testing. To assess the efficacy in the prevention of severe disease and asymptomatic infections, similar analyses to those performed on the primary efficacy endpoint will be performed. The efficacy will be demonstrated if the LL of the exact 2-sided 95% CI of VE is above 10% for severe disease and above 0% for asymptomatic infections. Measure:Occurrence of first episodes of virologically-confirmed (RT-PCR positive) severe cases of COVID-19 meeting the case definition for the primary efficacy analysis (severe COVID-19 disease defined in Appendix 3). Timepoints:6 months ; Outcome name:To assess the efficacy in the prevention of severe disease and asymptomatic infections, similar analyses to those performed on the primary efficacy endpoint will be performed. The efficacy will be demonstrated if the LL of the exact 2-sided 95% CI of VE is above 10% for severe disease and above 0% for asymptomatic infections. Measure:Occurrence of seroconversion to the N protein of SARS-CoV-2 ≥ 15 following after the second trial vaccination in asymptomatic seronegative subjects. Seroconversion is defined as detectable SARS-CoV-2 N protein antibodies in the serum of subjects on Day 211 and/or Day 393 of the trial, who tested seronegative at Day 1 (baseline) and Day 43 (i.e. at the 2 t | — |
Countries
Argentina, Belgium, Colombia, Dominican Republic, Germany, Mexico, Nederland, Peru, Spain
Contacts
Public ContactElizabeth Rospigliosi
RPS PERU S.A.C
Outcome results
None listed