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Precedia/Protein and VLP vaccines/Heplisav-B/First dose

Heplisav-B: how was the first human dose set?

hepatitis B vaccine (recombinant), adjuvanted · HBsAg; TLR9 (CpG 1018 adjuvant)
Check my plan vs. these
First-in-human starting dose
Not stated in public reviews
Why it's blank

The public FDA and EMA reviews of Heplisav-B don't say how the first human dose was chosen. That rationale is in the IND, which is confidential, so it is missing for most approved products.

How it's usually set for vaccines outside oncology

Find the highest dose with no adverse effects (NOAEL) in each animal species, convert it to a human equivalent dose, usually by body surface area, pick the most appropriate species, then divide by a safety factor (default 10) to get the maximum recommended starting dose.

“In general, one should consider using a safety factor of at least 10. The MRSD should be obtained by dividing the HED by the safety factor.”
✓ VerifiedFDA 2005: Estimating the Maximum Safe Starting Dose in Initial Clinical…, p. 7Source ↗
This product's starting point

NOAEL / key findings: Monkey NOAEL 0.5 mg/kg CpG 1018 (>10-fold clinical) for systemic immunostimulation; spleen and lymph node hyperplasia, liver inflammation at higher doses (EMA assessment report, p. 28)

Full method, every step sourced →

NOAEL / key findings
Monkey NOAEL 0.5 mg/kg CpG 1018 (>10-fold clinical) for systemic immunostimulation; spleen and lymph node hyperplasia, liver inflammation at higher doses
“It should be noted that other systemic manifestations of TLR9 immunostimulation were seen in monkeys (i.e. spleen hyperplasia from 2.5 mg/kg/w and lymph node hyperplasia and liver inflammation at 12.5 mg/kg/w). Of importance, a NOAEL of 0.5 mg/kg 1018 ISS (>10-fold the clinical dose on mg/kg basis) for systemic immunostimulatory effects was identified in this study.”
✓ VerifiedEMA assessment report, p. 28Source ↗

Same question, other vaccines

Flublok

influenza vaccine, recombinant hemagglutinin · Influenza HA
Antigen content of quadrivalent product matched licensed trivalent vaccine plus a second B strain; no separate dose-finding

PreHevbrio

hepatitis B vaccine (recombinant), 3-antigen · HBsAg S/pre-S1/pre-S2 VLPs
Selection not stated; legacy dose-ranging studies (5 and 10 µg), one with an initial first-in-human part up to 20 µg

Arexvy

respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)
Not stated for first-in-human; final 120 µg RSVPreF3 + 50 µg AS01E dose selected on clinical data

Cervarix

human papillomavirus bivalent (types 16, 18) vaccine, recombinant, AS04-adjuvanted · HPV 16/18 L1 VLPs; TLR4 (AS04 adjuvant)
Not stated in public reviews

Cyfendus

anthrax vaccine adsorbed, adjuvanted · B. anthracis PA; TLR9 (CpG 7909 adjuvant)
Not stated in public reviews

Fendrix

hepatitis B vaccine (rDNA), AS04C-adjuvanted · HBsAg VLPs; TLR4 (AS04C adjuvant)
Not stated in public reviews

Gardasil

human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant · HPV 6/11/16/18 L1 VLPs
Not stated in public reviews

Gardasil 9

human papillomavirus 9-valent vaccine, recombinant · HPV 9-valent L1 VLPs
Not stated in public reviews

HBVaxPro

hepatitis B vaccine (rDNA) · HBsAg VLPs
Not stated in public reviews

Mosquirix

RTS,S/AS01 malaria vaccine · P. falciparum CSP-HBsAg (RTS,S) VLPs; TLR4 (AS01 adjuvant)
Not stated in public reviews

Nuvaxovid

COVID-19 vaccine, recombinant spike protein nanoparticle, Matrix-M-adjuvanted · SARS-CoV-2 spike (nanoparticle)
Not stated in public reviews

Shingrix

zoster vaccine recombinant, AS01B-adjuvanted · VZV glycoprotein E; TLR4 (AS01B adjuvant)
Not stated in public reviews

Summary across all 13 vaccines →