Phase 1 trial to model primary, secondary, and tertiary dengue using a monovalent vaccine

Odio, Camila D.; Lowman, Kelsey E.; Law, Melissa; Aogo, Rosemary A.; Hunsberger, Sally; Wood, Brad J.; Kassin, Michael; Levy, Elliot; Callier, Viviane; Firdous, Saba; Hasund, Chloe M.; Voirin, Charlie; Kattappuram, Robbie; Yek, Christina; Manning, Jessica; Durbin, Anna; Whitehead, Stephen S.; Katzelnick, Leah C.

doi:10.1186/s12879-023-08299-5

BMC Infectious Diseases

Table 3 Schedule of Activities

From: Phase 1 trial to model primary, secondary, and tertiary dengue using a monovalent vaccine

	Screen	Optional^a	Schedule of Activities															Optional^b
Visit Number	Screen		SC^c	01	02	03	04	05	06	07	SC^c	08	SC^c	09	SC^c	10	11	12
Day of Study ^d			−59 to 0	D0	D1	D3	D6	D9	D12	D15	D16	D28	D29	D57	D58	D90	D180	D365
Visit Window (days)	−60 to − 1	−59 to 0	+ 2	0	0	± 2	± 2	± 2	± 2	± 4	+ 1	± 4	+ 1	+ 12	+ 1	± 10	± 15	± 15
Clinical Evaluations/ Procedures				Active Phase										Follow-up Phase
DENV3 vaccine screening consent	X
DENV3 vaccine full study informed consent^e		X		X
Demographics	X
Medical history/focused physical examination	X	X		X			X	X		X		X		X			X	X
Vital signs^f	X	X		X			X	X		X		X		X			X	X
Height/weight	X
Review of health history	X			X						X		X		X			X	X
Travel history assessment	X^g			X^h
Concomitant medication review	X	X		X			X	X		X		X		X			X	X
Pregnancy prevention counseling	X			X
Communication for any aspirate-related AEs			X								X		X		X
Administer rDEN3Δ30/31-7164 vaccineⁱ				X
AE assessment^j				X			X	X		X		X		X			X	X
Optional lymph node fine needle aspiration^k		X								X		X		X
DENV3 vaccine screening consent	X
Optional lymph node fine needle aspiration^k		X								X		X		X
Optional photos of rash, if present							X	X		X		X		X
CBC with differential	X^l	X		X	X	X	X	X	X	X		X		X
Acute care and hepatic panel	X	X		X				X	X	X		X		X
PT/PTT/INR	X	X		X				X	X	X		X		X
HBsAg, anti-HCV antibody	X
Anti-HIV 1/2 antibody/Ag	X
HLA typing				X
Human chorionic gonadotropin, pregnancy^m	X	X		X						X		X		X
Drug abuse screen, urine	X
Research blood (flavivirus antibodies, neutralizing antibody assays, serum storage, viral qRT-PCR, and culture)ⁿ	X			X	X	X	X	X	X	X		X		X		X	X	X
Research blood (T and B cell assays; plasma, PBMC storage)		X		X	X	X	X	X		X		X		X		X	X	X

Abbreviations: AE, adverse event; CBC, complete blood count; DENV, dengue virus; HbA1c, hemoglobin A1c; HBsAg, hepatitis B virus surface antigen; HCV, hepatitis C virus; HIV, human immunodeficiency virus; INR, international normalized ratio; OTC, over the counter; PBMC, peripheral blood mononuclear cells; PT, prothrombin time; PTT, partial thromboplastin time; qRT-PCR, quantitative reverse transcription polymerase chain reaction; SC, secure communication; X, to be performed
^aOptional visit for lymph node aspiration to obtain baseline cell populations
^bOptional blood draw on day 365 to assess antibody waning
^cAll patients who undergo lymph node aspiration will receive a follow-up call or secure electronic communication (per participant preference) within 24 to 48 h to assess for any procedure-related AEs.
^dAn early termination visit will be performed if the participant decides to discontinue participation or is withdrawn from the study prior to day 180. It will include a targeted history, focused physical exam, and assessment of any unresolved AEs, including abnormal laboratory results
^eWritten informed consent for screening must be obtained prior to initiation of screening procedures, and written informed consent for the DENV3 vaccination protocol must be obtained at the optional baseline lymph node aspiration day or day 0 prior to the initiation of any study procedures
^fComplete post-vaccination evaluation (temperature, blood pressure, pulse, respiratory rate, and injection site assessment) will be performed 30 to 60 min post-vaccination. For those undergoing lymph node aspiration, vital signs will also be assessed per Clinical Center and interventional radiology guidelines
^gShort travel history completed at pre-screening will only be reviewed by unblinded statistician to assist with screening target groups
^hPost-enrollment travel history assessment can be completed any time between days 0 and 57. Study staff will not review the assessment until after study unblinding
ⁱFor participants who can get pregnant, confirm that pregnancy test is negative on day 0, and for all participants, review safety labs from screening day (CBC, acute care, hepatic panels) prior to vaccine administration. Day 0 safety labs are for baseline only and will not determine eligibility
^jDay 0 evaluations, prior to the first vaccine dose, are the baseline for assessing subsequent AEs.
^kLymph fluid will be collected, with minimal blood loss anticipated (< 5 mL). Participants will be monitored post-procedure until the responsible provider deems they are safe to leave the Clinical Center. Lymph node aspirations on days 15 and 28 are opt-out procedures, and pre-vaccine and day 57 aspirations are opt-in procedures. Participants can choose to undergo any number of aspirates: from zero to four
^lHemoglobin A1c will be assessed as part of CBC on screening day only
^mNegative pregnancy test from day 0 will be confirmed prior to vaccination. Pregnancy testing will only be performed on days − 59 to − 14, 15, 28, and 57 if participants who can get pregnant undergo lymph node aspiration. Pregnancy test will be performed as part of the acute care panel, and additional volume is not required
ⁿAntibodies against DENV1-4 will be assessed in all individuals. Flavivirus antibodies may include yellow fever virus, West Nile virus, Japanese encephalitis virus, and Zika virus, among others. These will be assessed at screening if necessary to confirm vaccination, travel, and/or medical history

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