Safety and Immunogenicity of a Self-Amplifying RNA Vaccine Against Crimean-Congo Hemorrhagic Fever

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.

Blood samples will be collected from all participants in the study. Participants in groups 1, 2 and 4 will provide samples at screening and 8 additional visits. Participants in group 3 will provide samples at screening and 7 additional visits.

Participants will be requested to attend a combination of in person clinic visits and phone calls. Participants in groups 1, 2 and 4 will have 2 phone calls and 10 in-clinic visits. Two of the clinic visits will include administration of HDT-321 via IM injections. Participants in cohort 3 will have 1 phone call and 9 in-clinic visits. One of the clinic visits will include administration of HDT-321 via IM injection.

Protocol-defined solicited local and systemic AEs will be collected for 7 days following each study injection via memory aid. Other AEs will be collected for 28 days following each study injection. SAEs, AESIs, MAAEs and NOCDs will be collected from the first study injection through their entire study participation.