History of Changes for Study: NCT04896086

VRC 325: A Phase I Open-Label Clinical Trial to Evaluate the Dose, Safety, Tolerability and Immunogenicity of Mosaic Quadrivalent Influenza Vaccine Compared With a Licensed Inactivated Seasonal QIV, In Healthy Adults.

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Study Record Versions

Version	Submitted Date	Changes
1	May 20, 2021	None (earliest Version on record)
2	May 21, 2021	Study Status
3	May 22, 2021	Study Description, Study Status, Eligibility and Study Identification
4	May 25, 2021	Study Status
5	May 26, 2021	Study Status and Study Identification
6	October 7, 2021	Document Section and Study Status
7	October 8, 2021	Recruitment Status, Contacts/Locations, Study Status and References
8	October 13, 2021	Study Status
9	November 5, 2021	Study Status
10	March 15, 2022	IPDSharing and Study Status
11	March 16, 2022	Study Status
12	March 17, 2022	Study Status
13	March 18, 2022	Study Status
14	March 19, 2022	Study Status and Arms and Interventions
15	March 22, 2022	Study Status
16	March 23, 2022	Study Status
17	March 24, 2022	Study Status
18	March 25, 2022	Study Status
19	March 26, 2022	Study Status
20	March 30, 2022	Study Status
21	March 31, 2022	Study Status
22	April 1, 2022	Eligibility and Study Status
23	April 2, 2022	Study Status
24	April 5, 2022	Study Status
25	April 6, 2022	Study Status
26	April 7, 2022	Study Status
27	April 8, 2022	Study Status
28	April 9, 2022	Study Status
29	April 13, 2022	Study Status
30	April 14, 2022	Study Status
31	April 15, 2022	Study Status
32	April 16, 2022	Study Status
33	April 19, 2022	Study Status
34	April 20, 2022	Study Status
35	April 21, 2022	Study Status
36	April 22, 2022	Study Status
37	April 23, 2022	Study Design and Study Status
38	April 26, 2022	Study Status
39	April 27, 2022	Study Status
40	April 29, 2022	Study Status
41	May 2, 2022	Study Status
42	May 3, 2022	Study Status
43	May 4, 2022	Study Status
44	May 5, 2022	Study Status
45	May 6, 2022	Study Status
46	May 9, 2022	Study Status
47	May 10, 2022	Study Status
48	May 11, 2022	Study Status
49	May 12, 2022	Study Status
50	May 13, 2022	Study Status
51	May 16, 2022	Study Status
52	May 17, 2022	Study Status
53	May 18, 2022	Study Status
54	May 19, 2022	Study Status
55	May 20, 2022	Study Status
56	May 23, 2022	Study Status
57	May 24, 2022	Study Status
58	May 25, 2022	Study Status
59	May 26, 2022	Study Status
60	May 27, 2022	Study Status
61	May 31, 2022	Study Status
62	June 1, 2022	Study Status
63	June 2, 2022	Study Status
64	June 3, 2022	Study Status
65	June 6, 2022	Study Status
66	June 7, 2022	Study Status
67	June 8, 2022	Study Status
68	June 9, 2022	Study Status
69	June 10, 2022	Study Status
70	June 13, 2022	Study Status
71	June 14, 2022	Study Status
72	June 15, 2022	Study Status
73	June 17, 2022	Arms and Interventions and Study Status
74	June 21, 2022	Study Status
75	June 22, 2022	Study Status
76	June 23, 2022	Study Status
77	June 24, 2022	Study Status
78	June 27, 2022	Study Status
79	June 29, 2022	Study Status
80	June 30, 2022	Study Status
81	July 1, 2022	Study Status
82	July 5, 2022	Study Status
83	July 6, 2022	Study Status
84	September 7, 2022	Outcome Measures, Arms and Interventions, Eligibility, Study Description, Study Status and Study Identification
85	September 9, 2022	Study Status
86	September 13, 2022	Recruitment Status, Study Status, Contacts/Locations, Study Design and References
87	September 17, 2022	Study Status
88	November 10, 2022	Study Status and Contacts/Locations
89	January 13, 2023	Contacts/Locations and Study Status
90	January 19, 2023	Study Description and Study Status
91	January 20, 2023	Study Status
92	January 28, 2023	Study Status
93	March 9, 2023	Arms and Interventions and Study Status
94	March 25, 2023	Study Status
95	April 11, 2023	Study Status
96	April 15, 2023	Study Status
97	April 27, 2023	Study Status
98	May 5, 2023	Recruitment Status, Study Status, Contacts/Locations, Study Design and References
99	May 8, 2023	Study Status
100	July 31, 2023	Study Status
101	December 1, 2023	Contacts/Locations, Study Description and Study Status
102	December 7, 2023	Study Status
103	January 12, 2024	Contacts/Locations and Study Status
104	January 19, 2024	Study Status
105	January 20, 2024	Study Status
106	February 9, 2024	Recruitment Status and Study Status
107	February 23, 2024	Study Status
108	March 5, 2024	Document Section and Study Status

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	10000410
Brief Title:	VRC 325: A Phase I Open-Label Clinical Trial to Evaluate the Dose, Safety, Tolerability and Immunogenicity of Mosaic Quadrivalent Influenza Vaccine Compared With a Licensed Inactivated Seasonal QIV, In Healthy Adults.
Official Title:	VRC 325: A Phase I Open-Label Clinical Trial to Evaluate the Dose, Safety, Tolerability and Immunogenicity of Mosaic Quadrivalent Influenza Vaccine Compared With a Licensed Inactivated Seasonal QIV, In Healthy Adults.
Secondary IDs:	000410-I

Study Status


Record Verification:	May 19, 2021
Overall Status:	Recruiting
Study Start:	May 26, 2021
Primary Completion:	May 1, 2023 [Anticipated]
Study Completion:	May 1, 2023 [Anticipated]

First Submitted:	May 20, 2021
First Submitted that Met QC Criteria:	May 20, 2021
First Posted:	May 21, 2021 [Actual]

Last Update Submitted that Met QC Criteria:	May 20, 2021
Last Update Posted:	May 21, 2021 [Actual]

Sponsor/Collaborators


Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:

Study Description

Brief Summary:

This is a Phase I, open-label, dose escalation study to evaluate the dose, safety, tolerability, and immunogenicity of the mosaic quadrivalent influenza vaccine VRC-FLUMOS0111-00-VP (FluMos-v1). The hypotheses are that the FluMos-v1 vaccine is safe and tolerable and will elicit an immune response. The primary objective is to evaluate the safety and tolerability of the investigational vaccine in healthy adults. Secondary objectives are related to immunogenicity of the investigational vaccine and dosing regimen compared with the licensed inactivated seasonal Flucelvax(Registered Trademark) quadrivalent influenza vaccine (QIV) in Healthy Adults.

The investigational vaccine FluMos-v1 was developed by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases (NIAID) and is composed of the following 4 influenza strains:

Influenza A:

H1: A/Idaho/07/2018

H3: A/Perth/1008/2019

Influenza B:

B/Victoria lineage: B/Colorado/06/2017

B/Yamagata lineage: B/Phuket/3073/2013

FluMos-v1 is supplied in a single-use vial at a concentration of 180 mcg/mL.

The FDA licensed inactivated 2020-2021 QIV Flucelvax(Registered Trademark) was developed by Seqirus, Inc. and is composed of the following 4 influenza strains:

Influenza A:

H1: A/Hawaii/70/2019 (H1N1) pdm09-like virus

H3: A/Hong Kong/45/2019 (H3N2)-like virus

Influenza B:

B/Victoria lineage: B/Washington/02/2019-like virus

B/Yamagata lineage: B/Phuket/3073/2013-like virus

Flucelvax(Registered Trademark) is supplied in a single-use syringe at 15 mcg HA of each of the four influenza strains, for a total of 60 mcg HA per 0.5 mL dose.

FluMos-v1 and Flucelvax(Registered Trademark) will be administered intramuscularly (IM) in the deltoid muscle via needle and syringe.

Healthy adults between the ages of 18-50 years inclusive will be enrolled.

The study will evaluate the safety, tolerability and immunogenicity of a single dose of FluMos-v1 vaccine in a dose-escalation design. In Group 1A-1B, five subjects will receive a dose of 20 mcg of FluMos-v1. If the 20 mcg dose is assessed as safe and tolerable, enrollment will begin for Group 2A-2B.

In Group 2A-2B, subjects will receive a dose of 60 mcg of FluMos-v1. In Group 3A-3B, subjects will receive the licensed QIV Flucelvax(Registered Trademark) and may enroll at any time after the study is open to accrual.

The protocol requires 1 vaccination visit, about 8 follow-up visits, and a telephone contact on the day after vaccination. For all groups, solicited reactogenicity will be evaluated using a 7-day diary card. Assessment of vaccine safety will include clinical observation and monitoring of hematological and chemical parameters at clinical visits throughout the study.

Subjects will be evaluated for 40 weeks following vaccine administration and through an influenza season.

Detailed Description:

Influenza A:

H1: A/Idaho/07/2018

H3: A/Perth/1008/2019

Influenza B:

B/Victoria lineage: B/Colorado/06/2017

B/Yamagata lineage: B/Phuket/3073/2013

FluMos-v1 is supplied in a single-use vial at a concentration of 180 mcg/mL.

The FDA licensed inactivated 2020-2021 QIV Flucelvax(Registered Trademark) was developed by Seqirus, Inc. and is composed of the following 4 influenza strains:

Influenza A:

H1: A/Hawaii/70/2019 (H1N1) pdm09-like virus

H3: A/Hong Kong/45/2019 (H3N2)-like virus

Influenza B:

B/Victoria lineage: B/Washington/02/2019-like virus

B/Yamagata lineage: B/Phuket/3073/2013-like virus

Flucelvax(Registered Trademark) is supplied in a single-use syringe at 15 mcg HA of each of the four influenza strains, for a total of 60 mcg HA per 0.5 mL dose.

FluMos-v1 and Flucelvax(Registered Trademark) will be administered intramuscularly (IM) in the deltoid muscle via needle and syringe.

Healthy adults between the ages of 18-50 years inclusive will be enrolled.

Subjects will be evaluated for 40 weeks following vaccine administration and through an influenza season.

Conditions


Conditions:	Influenza Seasonal Influenza
Keywords:	Seasonal Influenza Flu Virus Respiratory Illness Viral Infection Experimental Vaccine

Study Design


Study Type:	Interventional
Primary Purpose:	Prevention
Study Phase:	Phase 1
Interventional Study Model:	Sequential Assignment
Number of Arms:	3
Masking:	None (Open Label)
Allocation:	Non-Randomized
Enrollment:	40 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: Group 1A-1B 20 mcg of FluMos-v1	Biological: VRC-FLUMOS0111-00-VP (FluMos-v1) The VRC-FLUMOS0111-00-VP (FluMos-v1) vaccine is composed of engineered pentamer yeast C. albicans lumazine synthase assembled with 20 HA ectodomain trimers from the following influenza strains: Influenza A (H1: A/Idaho/07/2018, H3: A/Perth/1008/2019) and Influenza B (B/Victoria lineage: B/Colorado/06/2017, B/Yamagata lineage: B/Phuket/3073/2013)
Experimental: Group 2A-2B 60 mcg of FluMos-v1	Biological: VRC-FLUMOS0111-00-VP (FluMos-v1) The VRC-FLUMOS0111-00-VP (FluMos-v1) vaccine is composed of engineered pentamer yeast C. albicans lumazine synthase assembled with 20 HA ectodomain trimers from the following influenza strains: Influenza A (H1: A/Idaho/07/2018, H3: A/Perth/1008/2019) and Influenza B (B/Victoria lineage: B/Colorado/06/2017, B/Yamagata lineage: B/Phuket/3073/2013)
Active Comparator: Group 3A-3B standard dose of 60 mcg of the licensed QIV Flucelvax	Biological: Flucelvax Flucelvax is a cell-based vaccine which contains the same four influenza strains selected by the WHO, and has shown better safety and immunogenicity profiles that the traditional licensed seasonal egg based vaccine

Outcome Measures


Primary Outcome Measures:
1.	Serious adverse events [ Time Frame: Day 0 through Day 280 ] Occurrence of serious adverse events
2.	New chronic medical conditions [ Time Frame: Day 0 through Day 280 ] Occurrence of new-onset of chronic medical conditions
3.	Local Reactogenicity [ Time Frame: 7 days after product administration ] Occurrence of local reactogenicity signs and symptoms
4.	Unsolicited adverse events [ Time Frame: Day 0 through 28 days post product administration ] Occurrence of unsolicited non-serious adverse events
5.	Laboratory measures [ Time Frame: Day 0 through 28 days post product administration ] Occurrence of laboratory safety measures
6.	Systemic Reactogenicity [ Time Frame: 7 days after product administration ] Occurrence of systemic reactogenicity signs and symptoms
Secondary Outcome Measures:
1.	Group 1A-1B: vaccine-induced antibodies [ Time Frame: 2 weeks after product administration ] antibody responses to FluMos-v1
2.	Group 2A-2B: vaccine-induced antibodies [ Time Frame: 2 weeks after product administration ] antibody responses to FluMos-v1

Eligibility


Minimum Age:	18 Years
Maximum Age:	50 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	Yes
Criteria:	INCLUSION CRITERIA: A subject must meet all of the following criteria: Healthy adults between the ages of 18-50 years inclusive Based on history and physical examination, in good general health and without history of any of the conditions listed in the exclusion criteria Received at least one licensed influenza vaccine from 2016 through the 2019-2020 influenza season Able and willing to complete the informed consent process Available for clinic visits for 40 weeks after enrollment and through an influenza season Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) <=35 within the 56 days before enrollment Laboratory Criteria within 56 days before enrollment White blood cells (WBC) and differential within institutional normal range or accompanied by the site Principal Investigator (PI) or designee approval Total lymphocyte count >=800 cells/microliter Platelets = 125,000 500,000 cells/microliter Hemoglobin within institutional normal range or accompanied by the PI or designee approval Alanine aminotransferase (ALT) <=1.25 x institutional upper limit of normal (ULN) Aspartate aminotransferase (AST) <=1.25 x institutional ULN Alkaline phosphatase (ALP) <1.1 x institutional ULN Total bilirubin within institutional normal range or accompanied by the PI or designee approval. Serum creatinine <=1.1 x institutional ULN Negative for HIV infection by an FDA-approved method of detection Negative for SARS-CoV-2 prior to enrollment Criteria applicable to women of childbearing potential: Negative beta-human chorionic gonadotropin (beta-HCG) pregnancy test (urine or serum) on the day of enrollment Agrees to use an effective means of birth control from at least 21 days prior to enrollment through the end of the study EXCLUSION CRITERIA: A subject will be excluded if one or more of the following conditions apply: Breast-feeding or planning to become pregnant during the study Subject has received any of the following substances: More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 4 weeks prior to enrollment or any within the 14 days prior to enrollment Blood products within 16 weeks prior to enrollment Live attenuated vaccines within 4 weeks prior to enrollment Inactivated vaccines within 2 weeks prior to enrollment Investigational research agents within 4 weeks prior to enrollment or planning to receive investigational products while on the study Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule Current anti-TB prophylaxis or therapy Previous investigational H1, H2, or H10 influenza vaccines Groups 1A, 2A, and 3A only: Receipt of the 2020-2021 season s licensed influenza vaccine at any time prior to enrollment Groups 1B, 2B, and 3B only: Receipt of the 2020-2021 season s licensed influenza vaccine within 4 months prior to enrollment. Subject has a history of any of the following clinically significant conditions: Serious reactions to vaccines that preclude receipt of the study vaccination as determined by the investigator Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema Asthma that is not well controlled Diabetes mellitus (type I or II), with the exception of gestational diabetes Thyroid disease that is not well controlled Idiopathic urticaria within the past year Autoimmune disease or immunodeficiency Hypertension that is not well controlled Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws Malignancy that is active or history of malignancy that is likely to recur during the period of the study Seizure disorder other than 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the last 3 years Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen Guillain-Barr(SqrRoot)(Copyright) Syndrome Previous or current infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) documented by PCR test Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a subject s ability to give informed consent.

Contacts/Locations


Central Contact Person:	Floreliz H Mendoza Telephone: (301) 451-8715 Email: mendozaf@mail.nih.gov
Study Officials:	Alicia T Widge, M.D. Principal Investigator National Institute of Allergy and Infectious Diseases (NIAID)
Locations:	United States, Maryland
	National Institutes of Health Clinical Center [Recruiting] Bethesda, Maryland, United States, 20892 Contact:Contact: VRC Clinic 301-451-8715 vaccines@nih.gov

IPDSharing


Plan to Share IPD:

References


Citations:	Lambert LC, Fauci AS. Influenza vaccines for the future. N Engl J Med. 2010 Nov 18;363(21):2036-44. doi: 10.1056/NEJMra1002842. No abstract available. PubMed 21083388
	Kanekiyo M, Joyce MG, Gillespie RA, Gallagher JR, Andrews SF, Yassine HM, Wheatley AK, Fisher BE, Ambrozak DR, Creanga A, Leung K, Yang ES, Boyoglu-Barnum S, Georgiev IS, Tsybovsky Y, Prabhakaran MS, Andersen H, Kong WP, Baxa U, Zephir KL, Ledgerwood JE, Koup RA, Kwong PD, Harris AK, McDermott AB, Mascola JR, Graham BS. Mosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses. Nat Immunol. 2019 Mar;20(3):362-372. doi: 10.1038/s41590-018-0305-x. Epub 2019 Feb 11. Erratum In: Nat Immunol. 2019 Apr 12;: PubMed 30742080
Links:	URL: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_000410-I.html Description: NIH Clinical Center Detailed Web Page
Available IPD/Information: