Safety and Immunogenicity of a Self-Amplifying RNA Vaccine Against Crimean-Congo Hemorrhagic Fever
brief summary
The goal of this clinical trial is to assess the safety, tolerability and immunogenicity of three dosage levels, and a single or two-dose administration regimen, of the investigational HDT-321 product administered intra-muscularly. The main questions it aims to answer are: * Is HDT-321 safe to use * Does HDT-321 provide protection against Crimean-Congo hemorrhagic fever virus (CCHFV) Researchers will record any adverse events and test blood samples to see if HDT-321 is safe and works to protect participants against Crimean-Congo hemorrhagic fever virus (CCHFV) Participants will: * Receive 1 or 2 doses of HDT-321 * Complete a memory aid and measurements for 7 days after receiving each dose of HDT-321 * Be followed throughout the study using phone calls and clinic visits to check for and record adverse events * Provide blood samples at specific study visits
detailed description
This is an open-label, dose-escalation, first-in-human study to evaluate the safety, reactogenicity and immunogenicity of the investigational product HDT-321 in approximately 48 healthy adults aged 18-64 years.
Four groups of 12 participants at three dosage levels will be sequentially recruited in the study, starting with the lowest dose. Groups 1, 2 and 4 will receive 2 doses and group 3 will receive 1 dose of HDT-321.
Study progression and dose escalation will occur according to the following:
Group 1 (10 μg): Three sentinel participants will be initially enrolled and followed for 7 days post-first study injection for safety assessment by predetermined objective criteria. If none of the pre-defined halting rules are met, as confirmed by the Safety Review Team (SRT), enrollment of the remaining participants of the group will proceed. In addition, available safety data for 7 days post-second study injection will be evaluated in the sentinel group prior to administering the second injection of the remaining participants of Group 1. Available safety data for 7 days post-first study injection of all participants will be reviewed by the SRT. If none of the pre-defined halting rules are met and no safety concerns have been identified, enrollment of Group 2 participants will proceed.
Group 2 (25 μg): In a similar fashion, three sentinel participants will be initially enrolled and followed for 7 days post-first study injection for safety assessment by predetermined objective criteria. If none of the pre-defined halting rules are met, as confirmed by the SRT, enrollment of the remaining participants of the group will proceed. In addition, available safety data for 7 days post second study injection will be evaluated in the sentinel group prior to administering the second injection of the remaining participants of Group 2. Available safety data for 7 days post-first study injection of all Group 1 and 2 participants along with any available post-second injection from Group 1 participants will be reviewed by the SRT. If none of the pre-defined halting rules are met and no safety concerns have been identified, enrollment of Groups 3 and 4 participants will proceed.
Groups 3 and 4 (50 μg): the same procedure with initial enrollment of three sentinel participants will be followed as outlined above, prior to enrollment of the remaining participants of Group 3 and all of Group 4. In addition, the available data 7 days post-first injection of the entire Group 3 and 4 along with available post-second injection data from Group 1 and 2 will be reviewed prior to administering the second dose of Group 4 participants.
official title
A Phase 1, Open Label, Dose-Escalation Study to Evaluate the Safety, Reactogenicity and Immunogenicity of a Nanoparticle Carrier-Formulated Self-Amplifying RNA Vaccine Against Crimean-Congo Hemorrhagic Fever (HDT-321) in Healthy Adults