Gintuit (allogeneic cultured keratinocytes and fibroblasts in bovine collagen): what was done before first-in-human, and what came after?

Precedia/Cell therapy/Gintuit/Tox package

Gintuit: what was done before first-in-human, and what came after?

allogeneic cultured keratinocytes and fibroblasts in bovine collagen · Allogeneic keratinocytes + fibroblasts

Before first-in-human

First-in-human: where

Not stated in public reviews

Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.

Repeat-dose tox before first-in-human

Not stated in public reviews

Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.

First-in-human starting dose

Not stated in public reviews

Why it's blank

The public FDA and EMA reviews of Gintuit 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 cell therapies

FDA expects preclinical proof-of-concept and toxicology studies to identify active dose levels and support the choice of starting dose and escalation. The 2013 guidance gives no numeric formula or scaling rule for the starting dose.

“Selection of potential starting dose level, dose-escalation schedule, and dosing regimen for clinical trials.”

✓ VerifiedFDA 2013: Preclinical Assessment of Investigational Cellular and Gene Therapy…, p. 7Source ↗

This product's starting point

NOAEL / key findings: No NOAEL; biocompatibility testing showed no findings of significant biological concern (FDA pharmacology/toxicology review, p. 49)

Full method, every step sourced →

Longest repeat-dose systemic studies

Longest repeat-dose study and recovery

No repeat-dose study (ICH chronic toxicology not conducted; nature of product and clinical experience)

“toxicology, chronic toxicology, genotoxicity, carcinogenicity, reproductive and developmental toxicity, safety pharmacology, and immunotoxicity (http://www.ich.org/cache/compo/276-254-1.html) were not conducted due to the nature of Apligraf® and the extensive clinical experience in the cutaneous indications.”