Tofacitinib for Immune Skin Conditions in Down Syndrome

  • STATUS
    Recruiting
  • End date
    Jul 12, 2023
  • participants needed
    46
  • sponsor
    University of Colorado, Denver
Updated on 12 December 2021
skin disorder
psoriasis
hidradenitis
tofacitinib
interferon
mediators
alopecia
atopy
dermatitis
areata alopecia
skin disease
vitiligo
alopecia areata
hidradenitis suppurativa
unbalanced translocation

Summary

People with Down syndrome (DS) display widespread immune dysregulation, including several immune skin conditions. This study hypothesizes that pharmacological inhibition of the increased interferon (IFN) signaling seen in DS is safe and could improve associated skin conditions.

The study evaluates the safety and efficacy treatment with Tofacitinib, an FDA-approved drug known to block IFN signaling, in adolescents and adults with DS and an autoimmune and/or autoinflammatory skin condition. Investigators will also measure the impact of interferon inhibition on a variety of molecular markers, as well as the cognitive abilities and quality of life of participants.

Description

Trisomy 21 (T21) is the most common human chromosomal disorder, occurring in ~1/700 live births, leading to the condition known as Down syndrome (DS). Importantly, people with DS display widespread immune dysregulation and over half of adults with T21 are affected by one or more autoimmune conditions, including several immune skin conditions. The driving hypothesis for this study is that hyperactivation of interferon (IFN) signaling leads to myriad immune-driven diseases and immunological phenotypes in people with DS, and that pharmacological inhibition of IFN signaling could have multidimensional therapeutic benefits in this population.

This study utilizes Tofacitinib, an FDA-approved drug known to block IFN signaling and several accompanying inflammatory pathways, to reduce IFN signaling in DS and to measure its effects via multidimensional endpoints. Previous studies and current clinical trials indicate that Janus kinase (JAK) inhibitors, such as Tofacitinib, can block inflammatory pathways and may have beneficial effects on immune skin conditions. Further, inhibition of chronically active IFN signaling in DS with Tofacitinib may attenuate other core drivers of immune dysregulation, leading to improvements in other immune diseases and conditions common to DS that are potentially driven by inflammation, such as cognitive deficits. Investigators will test these hypotheses using a battery of immune and molecular assessments, as well as cognitive testing and quality of life measures. This clinical trial evaluates adult participants with DS during eight study visits over an approximate five month period.

Specific Aims:

  1. To define the safety profile of JAK inhibition in people with DS,
  2. To determine the impact of JAK inhibition on the immune dysregulation caused by trisomy 21,
  3. To define the impact of JAK inhibition on immune skin conditions in DS, and
  4. To characterize the impact of JAK inhibition on cognition and quality of life in DS.

Details
Condition Down Syndrome, Alopecia Areata, Atopic Dermatitis / Eczema, Hidradenitis Suppurativa, Vitiligo, Psoriasis
Treatment tofacitinib
Clinical Study IdentifierNCT04246372
SponsorUniversity of Colorado, Denver
Last Modified on12 December 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Males or females with DS between 12 and 50 years of age who weigh at least 40 kg
Diagnosis of at least one active immune skin condition, including but not limited to
Moderate-to-severe atopic dermatitis
Alopecia areata affecting at least 25% of the scalp
Be willing to avoid pregnancy or fathering children
Moderate-to-severe hidradenitis suppurativa
Must present with a study partner or legal guardian who can complete, or assist with completing, study materials as appropriate
Moderate-to-severe psoriasis
Moderate-to-severe vitiligo

Exclusion Criteria

Poor venous access not allowing repeated blood tests or non-compliance with venipuncture requirements
Prior treatment with a JAK inhibitor or with an investigational agent, device, or procedure within 21 days of enrollment
Known allergies, hypersensitivity, or intolerance to Tofacitinib
History of thrombotic disorder
Weigh less than 40 kg
Superficial skin infection within 2 weeks of inclusion in the study
History of disseminated herpes zoster, disseminated herpes simplex, or recurrent localized dermatomal herpes zoster
Pregnancy or breast feeding
Intravenous antimicrobial therapy within 3 months of inclusion in the study
No study partner or legal guardian
Oral antimicrobials within 4 weeks of inclusion in the study
Vaccination with live attenuated virus within six weeks of inclusion in the study or planned during the study
Clinically significant chronic or active viral infection including but not limited to HIV, hepatitis, CMV, EBV, HSV
Participants may be excluded for other unforeseen reasons at the study doctor's discretion
Severe renal impairment
History of malignant solid tumor cancer within five years prior to study entry or where there is current evidence of recurrent or metastatic disease
Concomitant treatment with other immunosuppressants (e.g. corticosteroids, methotrexate) or strong CP3A4 or CYP2C19 inhibitors or inducers (e.g. ketoconazole, fluconazole)
Unable to provide assent in cases where informed consent is obtained from other authorized representative
Any history of heart attack or stroke
Kidney transplant within the last two years
Any history of lymphoma
Past or current smokers
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