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

NCT07598643 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-0432
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

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 (XELJANZ) 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).

Conditions

Down Syndrome

Keywords

Down syndrome; JAK inhibition; Tofacitinib

Outcome Measures

Primary Outcomes (6)

• Number and percentage of subjects experiencing treatment-emergent adverse events.

  Number, percentage, type, and severity of treatment-emergent adverse events (TEAEs) will be annotated over the 6-month period in the treatment arm and placebo arm.

  From screening to 1 month after end of treatment

• Change in Kaufman Brief Intelligence Test, 2nd Edition Revised (KBIT-2 Revised) - Verbal Intelligence

  Raw scores for Verbal Intelligence

  Baseline, 6 months

• Change in Kaufman Brief Intelligence Test, 2nd Edition Revised (KBIT-2 Revised) - Nonverbal Intelligence

  Raw scores for Nonverbal Intelligence

  Baseline, 6 months

• Change in Leiter 3 - Attention Sustained subtest

  The raw score is the correct number of targets minus errors made across four trials.

  Baseline, 6 months

• Change in Vineland Adaptive Behavior Scales 3 (VABS-3) - Sum of Domain Raw Scores

  The sum of raw scores will be calculated as the applicable domain-level raw scores.

  Baseline, 6 months

• Change in Clinical Global Impressions (CGI) Scale - Improvement in Health (CGI-I-H)

  The CGI-I scale, which ranges from 1 to 7, with 1 being "very much improved" and 7 being "very much worse" to assess changes in global health during the 6-month intervention period. Noteworthy, we will also collect the CGI-S score (severity) at each time point (baseline, 3 months - midpoint visit, and 6 months - endpoint visit). The CGI-I will be collected at 3 months and 6 months.

  Baseline, 6 months

Secondary Outcomes (13)

• Change in Peabody Picture Vocabulary Test, Fifth Edition (PPVT-5)

  Baseline, 6 months

• Change in Naturalistic Language Sample

  Baseline, 6 months

• Change in Achenbach Child (or Adult) Behavior Checklist

  Baseline, 6 months

• Change in Social Responsiveness Scale 2 (SRS-2), School Age and Adult

  Baseline, 6 months

• Change in Modified Corsi Span test

  Baseline, 6 months

Other Outcomes (1)

• Change in PedsQL

  Baseline, 6 months

Study Arms (2)

Treatment Arm

EXPERIMENTAL

Participants enrolled in the treatment arm will receive a 6-month treatment with the JAK1/3 inhibitor tofacitinib (XELJANZ) to define the safety and efficacy of this medicine relative to placebo.

Drug: Tofacitinib Oral Solution

Placebo arm

PLACEBO COMPARATOR

Participants in the placebo arm will complete the same study activities as the participants in the treatment arm. Placebo will be an oral solution to mimic the active product. At the end of 6 months of activities, unblinding will occur and if eligible, participants in the placebo arm may be offered to participate in the cross-over arm to undergo 6 months of treatment with tofacitinib in an open-label design.

Drug: Placebo

Interventions

Tofacitinib Oral Solution DRUG

JAK1/3 inhibitor

Also known as: XELJANZ

Treatment Arm

Placebo DRUG

The placebo will be compounded by Children's Hospital of Colorado Investigational Drug Services using commercially available syrup with added flavoring to mimic the active product.

Placebo arm

Eligibility Criteria

• Age: 6 Years - 22 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• 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.
• Evidence of severe organ dysfunction, including severe renal impairment, that at the determination of the treating physician would preclude safe administration of tofacitinib.
• Any history of leukemia, lymphoma, or unresolved transient myeloproliferative disorder.
• Any current, recurrent, or metastatic forms of cancer.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Anschutz Acceleration Initiative: collaborator
• GLOBAL Down Syndrome Foundation: collaborator

Study Sites (1)

CU Anschutz, Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

MeSH Terms

Conditions

Down Syndrome

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Study Officials

• Joaquin Espinosa, PhD

  Linda Crnic Institute for Down Syndrome, CU Anschutz

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Constance Brecl

CONTACT

303-724-6214; constance.brecl@cuanschutz.edu

Erika Chelales, PhD

CONTACT

303-724-5017; erika.chelales@cuanschutz.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All participants, caregivers, and study team members will remain blinded to the intervention. The only personnel who will be unblinded will be the study specialist running the randomization algorithm and personnel at the Investigational Drug Services Pharmacy at Children's Hospital of Colorado. Unblinding will occur at the conclusion of the month 6 visit (all clinical procedures must be complete prior to unblinding) to define whether the participant had been assigned to the treatment or placebo arms to determine eligibility for the open-label extension.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 2, double-blind, randomized, placebo-controlled clinical trial

Study Record Dates

• First Submitted: May 13, 2026
• First Posted: May 20, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2030
• Last Updated: May 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: Data will be made available upon publication in a peer-reviewed journal.
• Access Criteria: Data access requests will be reviewed by the sponsor-investigator and collaborators.

Locations

US (1)