Tofacitinib for Immune Skin Conditions in Down Syndrome

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-21

Study Completion Date

2024-10-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Antifungal Activity of Loceryl Nail Lacquer in Combination With a Cosmetic Varnish

NCT02321098

Foot Dermatoses

COMPLETED PHASE4

A Study to Evaluate TMI-358 in the Treatment of Distal Subungual Onychomycosis

NCT01093118

Distal Subungual Onychomycosis

TERMINATED PHASE2

Treatment of Mild to Moderate Distal Subungual Onychomycosis of the Toenail

NCT00453271

Onychomycosis

COMPLETED PHASE2

The Safety and Efficacy of Topical IDP-108 Versus Vehicle in Patients With Onychomycosis

NCT01007708

Onychomycosis

COMPLETED PHASE3

Safety and Efficacy of Topical IDP-108 Versus Vehicle in Patients With Onychomycosis

NCT01008033

Onychomycosis

COMPLETED PHASE3

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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 adolescent and 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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Down Syndrome Alopecia Areata Atopic Dermatitis / Eczema Hidradenitis Suppurativa Vitiligo Psoriasis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

All participants will receive the investigational product, Tofacitinib.

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

On Treatment

Tofacitinib 5mg oral tablets twice daily for 16 weeks

Group Type EXPERIMENTAL

Tofacitinib

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Tofacitinib

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

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Xeljanz

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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:

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

* Weigh less than 40 kg.
* Pregnancy or breast feeding.
* No study partner or legal guardian.
* 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.
* 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.
* 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 strong 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 2 weeks of inclusion in the study.
* Participants may be excluded for other unforeseen reasons at the study doctor's discretion.
* Unable to provide assent in cases where informed consent is obtained from other authorized representative.
* Kidney transplant within the last two years
* Any history of heart attack or stroke.
* Any history of lymphoma.
* Past or current smokers.

Minimum Eligible Age

12 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No