NCT05945485

A Study to Evaluate the Safety and Immunogenicity of Two Doses of DCVC H1 HA mRNA-LNP in Healthy Adults

A Phase 1, Comparator-Controlled, Dosage-Escalation Study to Evaluate the Safety and Immunogenicity of Two Doses of DCVC H1 HA mRNA-LNP in Healthy Adults

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 50 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 49 Years
• Healthy volunteers: Accepted

Summary

This is a Phase 1, single-site, comparator-controlled, dosage-escalating study of an intramuscularly administered mRNA-LNP vaccine encoding for DCVC H1 HA in up to 50 adult volunteers aged 18 to 49 years, inclusive. This study is designed to assess the safety and immunogenicity of two doses of DCVC H1 HA mRNA vaccine administered 28 days apart. Eligible participants will be sequentially enrolled into dosage escalation groups (10 mcg, 25 mcg, and 50 mcg). A separate group of 10 participants will receive one dose of the licensed quadrivalent influenza vaccine (IIV4). Enrollment of participants into the IIV4 group is limited to when the vaccine is available for a given year. Concurrent enrollment of the IIV4 group and any pre-specified study product group or groups may present logistical challenges due to the availability of the IIV4 vaccine and may preclude enrollment of all study participants prior to the subsequent off-season. Participants receiving IIV4 will be followed for safety but only their immune responses will be compared to those of participants receiving DCVC H1 HA mRNA vaccine. Dosing of DCVC H1 HA mRNA vaccine will commence at the lowest dose (10 mcg) and only escalate to the next highest dose if safety concerns are not identified. For each DCVC H1 HA mRNA vaccine dosing group, the first two participants enrolled will be considered the sentinel subgroup. After the two participants in the Low Dose sentinel subgroup are enrolled and given their first vaccination, enrollment and subsequent vaccinations in that dosing group will then be stopped until Day 3. This review will be conducted by a Safety Review Committee (SRC). If no halting criteria are met, the SRC will allow administration of the second dose for the sentinel subgroup and continued enrollment of the remaining 8 Low Dose Group participants (expanded subgroup) to complete enrollment of 10 participants. In order for a timely receipt of a second dose of study product on Day 29, SRC review and approval must occur prior to Study Day 28 for the first sentinel participant in the Low Dose Group. After the Low Dose Group enrollment is completed and both doses have been administered, enrollment will be stopped pending SRC review. After all participants in the Low Dose Group have completed the Day 36 visit, the SRC will review the clinical laboratory, reactogenicity, and adverse event information through the Day 36 visit for all Low Dose Group participants that received two doses. Approval by the SRC will allow dose escalation and initiation of enrollment of the Medium Dose Group sentinel subgroup. The Medium and High Dose sentinel and expanded groups will be enrolled as described above for the Low Dose sentinel and expanded groups, respectively, with the High Dose expanded subgroup enrolling up to 18 individuals. The primary objective of this study is to assess the safety of two doses of DCVC H1 HA mRNA Vaccine administered intramuscularly in healthy adults (18-49 yrs) at dosage levels of 10 mcg, 25 mcg, and 50 mcg.

Detailed description

This is a Phase 1, single-site, comparator-controlled, dosage-escalating study of an intramuscularly administered mRNA-LNP vaccine encoding for DCVC H1 HA in up to 50 adult volunteers aged 18 to 49 years, inclusive. This study is designed to assess the safety and immunogenicity of two doses of DCVC H1 HA mRNA vaccine administered 28 days apart. Eligible participants will be sequentially enrolled into dosage escalation groups (10 mcg, 25 mcg, and 50 mcg). A separate group of 10 participants will receive one dose of the licensed quadrivalent influenza vaccine (IIV4). Enrollment of participants into the IIV4 group is limited to when the vaccine is available for a given year. Concurrent enrollment of the IIV4 group and any pre-specified study product group or groups may present logistical challenges due to the availability of the IIV4 vaccine and may preclude enrollment of all study participants prior to the subsequent off-season. Participants receiving IIV4 will be followed for safety but only their immune responses will be compared to those of participants receiving DCVC H1 HA mRNA vaccine. Dosing of DCVC H1 HA mRNA vaccine will commence at the lowest dose (10 mcg) and only escalate to the next highest dose if safety concerns are not identified. For each DCVC H1 HA mRNA vaccine dosing group, the first two participants enrolled will be considered the sentinel subgroup. After the two participants in the Low Dose sentinel subgroup are enrolled and given their first vaccination, enrollment and subsequent vaccinations in that dosing group will then be stopped until Day 3. This review will be conducted by a Safety Review Committee (SRC). If no halting criteria are met, the SRC will allow administration of the second dose for the sentinel subgroup and continued enrollment of the remaining 8 Low Dose Group participants (expanded subgroup) to complete enrollment of 10 participants. In order for a timely receipt of a second dose of study product on Day 29, SRC review and approval must occur prior to Study Day 28 for the first sentinel participant in the Low Dose Group. After the Low Dose Group enrollment is completed and both doses have been administered, enrollment will be stopped pending SRC review. After all participants in the Low Dose Group have completed the Day 36 visit, the SRC will review the clinical laboratory, reactogenicity, and adverse event information through the Day 36 visit for all Low Dose Group participants that received two doses. Approval by the SRC will allow dose escalation and initiation of enrollment of the Medium Dose Group sentinel subgroup. The Medium and High Dose sentinel and expanded groups will be enrolled as described above for the Low Dose sentinel and expanded groups, respectively, with the High Dose expanded subgroup enrolling up to 18 individuals. The primary objective of this study is to assess the safety of two doses of DCVC H1 HA mRNA Vaccine administered intramuscularly in healthy adults (18-49 yrs) at dosage levels of 10 mcg, 25 mcg, and 50 mcg. The secondary objective of this study is to assess the serum antibody responses to two doses of DCVC H1 HA mRNA Vaccine administered intramuscularly 28 days apart in healthy adults at dosage levels of 10 mcg, 25 mcg, and 50 mcg in comparison to a standard dose of IIV4.

Conditions

• Influenza

Interventions

Type	Name	Description
BIOLOGICAL	DCVC H1 HA mRNA vaccine	A modified nucleoside messenger RNA (mRNA) vaccine encoding the full length HA of influenza A/California/07/2009 (H1N1) encapsulated in lipid nanoparticle (LNP) composed of ionizable lipid, DSPC, cholesterol, and PEG lipid for delivery
BIOLOGICAL	Quadrivalent Recombinant Seasonal Influenza Vaccine	The vaccine contains recombinant hemagglutinin (HA) proteins from four influenza viruses, expressed using a baculovirus vector. These HA proteins are produced in a continuous insect cell line.
OTHER	Sodium Chloride, 0.9%	0.9% Sodium Chloride Injection

Timeline

• Start date: 2023-10-16
• Primary completion: 2026-06-01
• Completion: 2026-06-01
• First posted: 2023-07-14
• Last updated: 2026-04-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study