Nonclinical precedent Request an invite
Precedia/Protein and VLP vaccines/Gardasil/First dose

Gardasil: how was the first human dose set?

human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant · HPV 6/11/16/18 L1 VLPs
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 Gardasil 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 oncology vaccines (ICH S9)

HNSTD/STD10 is the method used for anticancer drugs in patients: the start dose is one-sixth of the highest non-severely toxic dose (HNSTD) in non-rodents, or one-tenth of the dose severely toxic to 10% of rodents (STD10), scaled by body surface area. The aim is a dose that is pharmacologically active yet reasonably safe.

“A common approach for many small molecules is to set a start dose at 1/10 the Severely Toxic Dose in 10% of the animals (STD 10) in rodents. If the non-rodent is the most appropriate species, then 1/6 the Highest Non-Severely Toxic Dose (HNSTD) is considered an appropriate starting dose.”
✓ VerifiedICH 2009: ICH S9: Nonclinical Evaluation for Anticancer Pharmaceuticals, p. 13Source ↗
This product's starting point

NOAEL / key findings: No systemic toxicity; iliac lymph node enlargement/hyperplasia and injection-site inflammation in mice (EMA assessment report, p. 8)

Full method, every step sourced →

NOAEL / key findings
No systemic toxicity; iliac lymph node enlargement/hyperplasia and injection-site inflammation in mice
“There was a treatment-related enlargement of the iliac lymph nodes. Treatment-related microscopic changes were noted in lymph nodes (hyperplasia) and in the muscle at the injection sites (inflammation).”
✓ VerifiedEMA assessment report, p. 8Source ↗

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 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

Heplisav-B

hepatitis B vaccine (recombinant), adjuvanted · HBsAg; TLR9 (CpG 1018 adjuvant)
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 →