Tofacitinib for Immune Skin Conditions in Down Syndrome

• Status: Recruiting
• Trial end date: 2023-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Colorado, Denver
• Collaborator: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Treatments: Tofacitinib

Criteria

Inclusion Criteria:

• Males or females with DS between 12 and 60 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 4 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.