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

Trial details

Who runs it

University of Colorado, Denver

Trial code

NCT07598643

Record updated

3 September 2026

Original description

This protocol describes a phase 2, double-blind, randomized, placebo-controlled clinical trial for Janus kinase (JAK) inhibition in Down syndrome (DS). This trial will evaluate the safety and efficacy of a 6-month treatment with the JAK1/3 inhibitor tofacitinib in individuals ages 6-22 (inclusive) with DS. There will be two main arms for this study: a treatment arm and a placebo control arm. Participants will be randomized into the treatment or placebo arm. Those completing 6 months in the placebo arm may be eligible to participate in a cross-over, open-label extension arm to receive 6 months of tofacitinib treatment. Participants will be evaluated during a Screening visit to determine eligibility, complete a Baseline visit if eligible, and be monitored via safety clinical laboratories and in-person evaluations by study doctors at 1 month, 3 months (mid-point visit) and 6 months (endpoint visit). An interim analysis of safety will be completed by an independent Data and Safety Monitoring Board (DSMB) after 40 participants have completed 6 months of treatment or placebo (20 in each arm).Read full original descriptionShow less

This protocol describes a phase 2, double-blind, randomized, placebo-controlled clinical trial for Janus kinase (JAK) inhibition in Down syndrome (DS). This trial will evaluate the safety and efficacy of a 6-month treatment with the JAK1/3 inhibitor tofacitinib in individuals ages 6-22 (inclusive) with DS. There will be two main arms for this study: a treatment arm and a placebo control arm. Participants will be randomized into the treatment or placebo arm. Those completing 6 months in the placebo arm may be eligible to participate in a cross-over, open-label extension arm to receive 6 months of tofacitinib treatment. Participants will be evaluated during a Screening visit to determine eligibility, complete a Baseline visit if eligible, and be monitored via safety clinical laboratories and in-person evaluations by study doctors at 1 month, 3 months (mid-point visit) and 6 months (endpoint visit). An interim analysis of safety will be completed by an independent Data and Safety Monitoring Board (DSMB) after 40 participants have completed 6 months of treatment or placebo (20 in each arm).

Inclusion: 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.

Exclusion: 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.

ClinicalTrials.gov NCT07598643