Tofacitinib for Immune Skin Conditions in Down Syndrome

Study Purpose

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 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years - 60 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Adults with Down syndrome between 18 and 60 years of age.
  • - A cytogenetic diagnosis of full T21 or complete unbalanced translocation of chromosome 21.
  • - Diagnosis of at least one active immune skin condition, including but not limited to 1) moderate-to-severe atopic dermatitis, 2) alopecia areata affecting at least 25% of the scalp, 3) moderate-to-severe hidradenitis suppurativa, 4) moderate-to-severe psoriasis, 5) moderate-to-severe vitiligo - Be willing to avoid pregnancy or fathering children.
  • - Must present with a study partner or legal guardian who can complete, or assist with completing, study materials as appropriate.

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.
  • - Concomitant treatment with other immunosuppressants (e.g. corticosteroids, methotrexate) or CP3A4 or CYP2C19 inhibitors or inducers (e.g. ketoconazole, fluconazole).
  • - Known allergies, hypersensitivity, or intolerance to Tofacitinib.
  • - History of thrombotic disorder.
  • - 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.
  • - Intravenous antimicrobial therapy within 3 months of inclusion in the study.
  • - Oral antimicrobials within 4 weeks of inclusion in the study.
  • - Participants may be excluded for other unforeseen reasons at the study doctor's discretion.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04246372
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Colorado, Denver
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Joaquin Espinosa, PhDCory Dunnick, MDDavid Norris, MD
Principal Investigator Affiliation Linda Crnic Institute, University of Colorado Anschutz Medical CampusDepartment of Dermatology, University of Colorado Anschutz Medical CampusDepartment of Dermatology, University of Colorado Anschutz Medical Campus
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherNIH
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Down Syndrome, Alopecia, Atopic Dermatitis/Eczema, Hidradenitis Suppurativa, Vitiligo, Psoriasis
Study Website: View Trial Website
Additional Details

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.

Arms & Interventions

Arms

Experimental: On Treatment

Tofacitinib 5mg oral tablets twice daily for 16 weeks

Interventions

Drug: - Tofacitinib

Treatment with oral Tofacitinib for immune mediated skin conditions in adults with Down syndrome

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Linda Crnic Institute for Down Syndrome, Aurora, Colorado

Status

Recruiting

Address

Linda Crnic Institute for Down Syndrome

Aurora, Colorado, 80045

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