A clinical trial to assess whether a self-amplifying ribonucleic acid (saRNA) vaccine against Rabies viruses is safe and induces immune responses

INTERVENTION: 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 CONDITION: Rabies ; Infections and Infestations PRIMARY OUTCOME: The safety of a self‐amplifying ribonucleic acid (saRNA) vaccine encoding the surfaceglycoprotein of Rabies virus, assessed using:; 1. Solicited local injection site reactions starting within 7 days of administration of the vaccine: pain, tenderness, erythema, swelling. These will be measured using a participant diary card.; 2. Solicited systemic reactions starting within 7 days of administration of the vaccine: pyrexia, fatigue, myalgia, headache, chills, arthralgia. These will be measured using a participant diary card; 3. Unsolicited adverse reactions (ARs) recorded throughout the trial period (including serious ARs); 4. Serious adverse events recorded throughout the trial period; 5. Unsolicited adverse events recorded throughout the trial period SECONDARY OUTCOME: The immunogenicity of a self‐amplifying ribonucleic acid (saRNA) vaccine encoding the surface glycoprotein of Rabies virus, measured using the titre of vaccine‐induced neutralising antibody responses to the Rabies virus surface glycoproteins at 4 weeks after the second vaccinations INCLUSION CRITERIA: 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