A phase I clinical trial to assess the reactogenicity, tolerability and immunogenicity of a self-amplifying ribonucleic acid (saRNA) vaccine encoding the surface glycoprotein of rabies virus (RAB-Vac)
Rabies
RAB-Vac is a single-blinded, randomised Phase I trial using the online tool “sealed envelope” to generate randomisation lists. Healthy participants aged 18-50 years will be enrolled at a single centre and immunised with a self-amplifying ribonucleic acid (saRNA) vaccine; LNP-RABVsaRNA-01 via the intramuscular route at three timepoints. There will be 6 groups with 8 participants per group. A total of 48 participants will be recruited to the trial. Blood samples will be collected for safety and immunogenicity analysis at follow-up visits on days 0, 1, 14, 28, 29, 56, 70, 84, 168, 169, 182, 196, 252, 532 (Groups 1-3) and days 0, 1, 14, 28, 84, 85, 98, 112, 168, 169, 182, 196, 252, 532 (Groups 4-6). Group 1 receives 0.2 μg/dose of LNP-RABVsaRNA-01 (Rabies glycoprotein RNA) at weeks 0,4, 24 weeks Group 2 receives 1 μg/dose of LNP-RABVsaRNA-01 (Rabies glycoprotein RNA) at weeks 0,4, 24 weeks Group 3 receives 5 μg/dose of LNP-RABVsaRNA-01 (Rabies glycoprotein RNA) at weeks 0,4, 24 weeks Group 4 receives 0.2 μg/dose of LNP-RABVsaRNA-01 (Rabies glycoprotein RNA) at weeks 0,12, 24 weeks Group 5 receives 1 μg/dose of LNP-RABVsaRNA-01 (Rabies glycoprotein RNA) at weeks 0,12, 24 weeks Group 6 receives 5 μg/dose of LNP-RABVsaRNA-01 (Rabies glycoprotein RNA) at weeks 0,12, 24 weeks
1. Healthy adults, aged 18-50 years on the day of screening 2. Willing and able to provide written informed consent 3. If female and of childbearing potential, willing to use a highly effective method of contraception from screening until 18 weeks after last injection 4. If male and not sterilised, willing to avoid impregnating female partners from screening until 18 weeks after last injection 5. Willing to avoid all other vaccines from within 4 weeks before and after the first and second injection 6. Willing and able to comply with visit schedule, complete online diaries and provide samples 7. Willing to abstain from donating blood for 3 months after the end of their participation in the trial or longer, if necessary 8. Willing to grant authorised persons access to his/her trial-related medical record and GP records either directly or indirectly 1. A woman will be considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A post-menopausal state is defined as no menses for 18 months without an alternative medical cause. 2. The following methods are considered highly effective: 2.1. Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation – oral, intravaginal or transdermal 2.2. Progestogen-only hormonal contraception associated with inhibition of ovulation – oral, injectable or implantable 2.3. Intrauterine device (IUD) 2.4. Intrauterine hormone-releasing system (IUS) 2.5. Bilateral tubal occlusion 2.6. Vasectomised partner, where the vasectomised partner has received medical assessment of the surgical success 2.7. Sexual abstinence, defined as refraining from heterosexual intercourse – must be the preferred and usual lifestyle of the participant 3. Nonclinical studies of saRNAs showed maximal expression of the vaccine immunogen at 7 days post-immun
1. Pregnant or lactating 2. Has a significant clinical history, physical finding on clinical examination during screening, or presence of a disease that is active or requires treatment to control it, including cardiac, respiratory, endocrine, metabolic, autoimmune, liver, neurological, oncological, psychiatric, immunosuppressive/immunodeficient or other disorders which in the opinion of the investigator is not compatible with healthy status, may compromise the volunteer’s safety, preclude vaccination or compromise interpretation of the immune response to vaccine. Individuals with mild/moderate, well-controlled comorbidities are allowed. 3. History of rabies infection 4. History of anaphylaxis or angioedema 5. History of severe or multiple allergies to drugs or pharmaceutical agents 6. History of severe local or general reaction to vaccination defined as: 6.1. Local: extensive, indurated redness and swelling involving most of the arm, not resolving within 72 hours 6.2. General: fever ≥39.5 °C within 48 hours; bronchospasm; laryngeal oedema; collapse; convulsions or encephalopathy within 72 hours 7. Have ever received an experimental or authorised vaccine against Rabies virus 8. Receipt of any immunosuppressive agents within 18 weeks of screening by any route other than topical 9. Detection of antibodies to hepatitis C 10. Detection of antibodies to HIV 11. Grade 1i and above abnormalities in routine laboratory parameters (see Table 4) using the FDA toxicity table Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, taking account of local laboratory reference ranges. https://www.fda.gov/media/73679/download 12. Participating in another clinical trial with an investigational drug or device or treated with an investigational drug within 28 days of screening. 13. Has received an immunisation within 28 days of screening Trace of protein and/or blood on dipstick urinalysis and ALT/AST ≤1.2 x ULN are not exclus