Gintuit
allogeneic cultured keratinocytes and fibroblasts in bovine collagen
Species
MouseRabbitOther
Longest study
52 wk
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Not conducted Not conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Athymic (nude) mice for pharmacology; rabbits, guinea pigs, mice for biocompatibility
“Species: Athymic mice, 6-8 weeks old; the number, strain and sex were not provided in the study report”
Why that species
Immunodeficient mice used so human cells could engraft and persist; no species rationale stated
“The transplanted Apligraf® remained durable, as demonstrated by the persistence of human keratinocytes and fibroblasts, for at least one year in the nude mice.”
Surrogate molecule
No surrogate; clinical construct (Apligraf) grafted onto nude mice
“Apligraf® appeared to function as a skin graft (i.e., healing by primary intention) in the nude mouse full-thickness wound model.”
Study lengthopen answer page →
Longest pivotal study
52 weeks
“Grafts were harvested at 7, 14, 28, 56, 100, 180, 232, and 365 days after grafting.”
Pivotal GLP studies
No GLP repeat-dose tox; GLP ISO-10993 biocompatibility tests (systemic, subchronic subcutaneous in rabbits) and non-GLP nude mouse graft studies
“The potential toxicity of Apligraf® was evaluated via studies that reflect the initial medical device framework (i.e., biocompatibility testing in conformance to ISO-10993 standards).”
Route in tox
Topical graft (mouse); intraperitoneal, intravenous, intracutaneous, subcutaneous extracts in biocompatibility
“Sub-chronic Toxicity (Subcutaneous Injection Test – Subchronic)”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (nature of product and clinical experience)
“The toxicology study designs as discussed in the International Conference on Harmonisation (ICH) Safety (‘S’) guidelines, consisting of pharmacokinetics, acute toxicology, chronic toxicology, genotoxicity, carcinogenicity, reproductive and”
Carcinogenicity
Not conducted (nature of product and clinical experience)
“were not conducted due to the nature of Apligraf® and the extensive clinical experience in the cutaneous indications.”
Reproductive & developmental
Not conducted (nature of product and clinical experience)
“were not conducted due to the nature of Apligraf® and the extensive clinical experience in the cutaneous indications.”
Safety pharmacology
Not conducted (nature of product and clinical experience)
“were not conducted due to the nature of Apligraf® and the extensive clinical experience in the cutaneous indications.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
NOAEL / key findings
No NOAEL; biocompatibility testing showed no findings of significant biological concern
“This biocompatibility testing paradigm did not reveal any findings of significant biological concern.”
Risksopen answer page →
Immune & cytokine safety
No alloimmune response in vitro; indirect allorecognition not evaluated; xenogeneic reaction to subcutaneous injection in rabbits
“The potential for Apligraf® to induce an alloimmune response by indirect allorecognition was not evaluated.”
Biodistribution & persistence
Human keratinocytes and fibroblasts persisted at least 1 year in nude mice; did not persist in humans
“The grafted keratinocytes and fibroblasts persisted for at least 1 year after grafting.”
Modality-specific risk
Alloimmune response and graft persistence/integration; hypertrophic scarring
“Apligraf® did not integrate or show long-term persistence following application to cutaneous wounds in humans; the mechanism for this species difference was not explored.”