Cicatricial Alopecia Clinical Trial
Official title:
A Pilot Study to Assess Safety and Biomarker Responses of the Dual JAK1/TYK2 Inhibitor for Cicatricial Alopecia
Alopecia could be subdivided into two main groups of diseases: non-scarring alopecia, such as male pattern baldness, or alopecia areata (AA), in which hair follicles are preserved, yet quiescent, and scarring alopecia, also known as cicatricial alopecia (CA), in which hair follicles are irreversibly destroyed. CA leads to scarred areas, most commonly on the scalp, that cannot re-grow hair. Despite being a long-term condition, that often has significant impact on patients' well-being, available effective treatments for these diseases are lacking. In addition, the molecular abnormalities causing CA are largely unknown. The study team's research involves administrating patients a new investigational drug (a combined TYK/JAK inhibitor) which has been shown to be safe and well tolerated in clinical studies to date, and is being investigated in other conditions, such as AA. CA patients will be asked to provide small samples of skin and blood throughout the treatment period, to find out how they respond to the drug, and to attempt to better understand these diseases.
JAK inhibitors are a group of small molecules, recently emerging as an appealing class of immune modifiers in dermatology. These are antagonists of the various members of the JAK enzymes family, which consists of JAK1, JAK2, JAK3, and tyrosine kinase-2 (TYK2). JAKs enable the binding and activation of the transducer and activator of transcription (STAT), by phosphorylating the cytoplasmic domain of multiple cytokine receptors. This results in translocation of the STAT into the nucleus, which greatly affects transcription. JAK antagonism therefore blocks this signaling through STAT activation, targeting Th1/IFN-γ as well as common γc cytokines (shared between IL-2, IL-4, IL-9, IL-7, IL-15 and IL-21), and TYK2 also adds an IL-23 capability. Therefore PF-06700841, a dual inhibitor of JAK1 and TYK2, currently being investigated for a number of indications including psoriasis, Crohn's disease, ulcerative colitis, psoriatic arthritis, atopic dermatitis, psoriasis, systemic lupus erythematosus and AA, and which has been shown to be safe and well tolerated, with good safety profile, was chosen for this protocol. The study team will evaluate scalp and blood markers of inflammation, hair keratins and fibrosis, and our ultimate goal would be to elucidate the relations between inflammation and tissue scarring. While the study design is specifically powered to detect mechanistic tissue effects of PF-06700841, drug safety and tolerability in this patient population will also be closely monitored. The study team's research proposal is novel in that the team proposes to investigate the immune profile of CA patients in skin and blood, at baseline, as well as during treatment with PF-06700841. In addition to the much-needed, prospective investigation of a new treatment modality for these diseases, the study team also aims to better characterize these diseases molecularly, and attempt to determine the effects of the inflammatory process on the resultant fibrosis. These findings will help to identify new treatment targets as well as direct further investigation for the development of new therapies for these disfiguring diseases. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT04472715 -
Hair Transplantation in Cicatricial Alopecia
|
N/A | |
| Recruiting |
NCT05549934 -
Ritlecitinib for Cicatricial Alopecia
|
Phase 2 |