Modulation of the Immune System in Down Syndrome for Improved Outcomes and Neurodevelopment - 1

Who can take part

• Individuals with DS aged 6 years (inclusive) to 22 years (inclusive). All forms of DS will qualify, including complete trisomy 21, Robertsonian translocation trisomy 21, partial trisomy 21 (segmental duplication), and/or mosaic trisomy 21
• Available parent(s) or guardian(s) legally able to sign the consent form and who can complete study materials as appropriate
• Body weight is at least 10 kgs

Who cannot take part

• Prior treatment with a JAK inhibitor or with an investigational agent, device, or procedure within 21 days of enrollment
• Current or planned use of a JAK inhibitor during the 6-month study period
• Vaccination with live attenuated virus within six weeks of inclusion in the study or planned during the study; Note on vaccines: Participants not yet vaccinated for MMR-V should consider their timeline for MMR-V vaccination. Specifically, the study team recommends MMR-V vaccination as soon as possible and delay study start until 6 weeks after MMR-V vaccinations
• Concomitant treatment with any of the following:; Concomitant treatment with other immunosuppressants (e.g., methotrexate, azathioprine, tacrolimus, cyclosporine); Strong CYP3A4 inhibitors (e.g., ketoconazole); Strong CYP3A4 Inducers (e.g., rifampin); Moderate CYP3A4 inhibitor(s) with a strong CYP2C19 inhibitor(s) (e.g., fluconazole); Other supplements or medications that at the determination of the treating physician would preclude safe use of tofacitinib
• Any cancer treatment within five years prior to study entry
• Intravenous antimicrobial therapy within 3 months of inclusion in the study
• Participant received blood or plasma products within 30 days of the Baseline visit
• Treatment with intravenous immunoglobulin (IVIG) within 8 weeks of the Baseline visit
• Less than 6 weeks post-surgery at Baseline appointment
• Known allergies, hypersensitivity, or intolerance to tofacitinib
• Active, uncontrolled, or life-threatening infection that at the determination of the treating physician would preclude safe use of tofacitinib
• History of gastrointestinal perforation
• Any history of leukemia, lymphoma, or unresolved transient myeloproliferative disorder
• Any current, recurrent, or metastatic forms of cancer
• Known personal history of thrombosis or bleeding disorder
• History of tuberculosis, disseminated herpes zoster, disseminated herpes simplex, or recurrent localized herpes zoster
• History of organ or bone marrow transplant
• History of myocardial infarction or stroke
• History of neurological syndrome that in the opinion of the study doctors would inhibit successful participation in the study
• Evidence of severe organ dysfunction, including significantly abnormal laboratory values or severe renal impairment, that at the determination of the treating physician would preclude safe administration of tofacitinib
• Evidence of lipid disorder, including but not limited to LDL > 190 mg/dL, per discretion of the treating physician
• Hospitalization longer than 6 months in the last year
• Total vision or hearing loss (with no corrective devices available)
• Participant must be able to attempt the neurodevelopment assessment battery at Baseline and caregiver must be able to complete proxy reports for neurodevelopmental assessments
• Poor venous access not allowing repeated blood tests or non-compliance with venipuncture requirements
• Participants may be excluded for other unforeseen reasons at the study doctor's discretion
• Pregnancy or breastfeeding
• Use of estrogen-containing oral contraceptives