A Phase 2 interventional study of Tofacitinib Oral Solution and Placebo in Down Syndrome, sponsored by University of Colorado, Denver. Recruiting at 1 site in United States. Open to participants aged 6 Years to 22 Years. Per ClinicalTrials.gov, last updated 2026-09-03.
Sponsored by University of Colorado, Denver · Phase 2, Interventional, and Treatment
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).
This is a phase 2 randomized, double-blind, placebo-controlled clinical trial for Janus kinase (JAK) inhibition in Down syndrome (DS). After successful enrollment, including informed consent and assessment of inclusion and exclusion criteria, participants will be enrolled and randomized into the treatment or placebo arms and complete identical activities over the course of 6 months.
Briefly, the study recruitment goal is 80 participants (n=40 per treatment and placebo arm) with up to 92 participants enrolled. Participants enrolled in the treatment arm will receive a 6-month treatment with the JAK1/3 inhibitor tofacitinib to define the safety and efficacy of this medicine relative to placebo.
Safety monitoring will be completed over the 6-month period through a combination of self-reporting, laboratory testing, and study doctor assessment. AEs will be annotated by the study team and classified per Common Terminology Criteria for Adverse Events (CTCAE 6.0).
Diverse metrics of neurodevelopment and overall health will be obtained at the Baseline visit, 3-month visit (midpoint) and 6-month visit (endpoint). The data obtained after 6 months of treatment or placebo will be used for all endpoint analyses.
Participants enrolled in the placebo arm will be eligible to continue in the trial for an additional 6 months of tofacitinib treatment in a cross-over, open-label extension arm. Data collected during the cross-over, open-label extension arm will not contribute to any of the primary endpoint analyses. Rather, the cross-over dataset will be used to complete exploratory analyses of longitudinal intra-individual variability while on placebo and tofacitinib. Activities during 6 months of treatment in the cross-over arm will be identical to the main treatment arm. The cross-over arm will also serve to incentivize participation by ensuring that all eligible participants will be able to receive the medicine at some point during the trial.
438 studies on the registry are indexed under Down Syndrome; 99 are open to participants now.
This study's planned enrollment of 92 is above the median of 37 across 286 interventional studies indexed under Down Syndrome.
Browse Down Syndrome studies →University of Colorado, Denver is the lead sponsor of 1,543 studies on the registry; 317 are open to participants now.
Of its 147 completed or terminated interventional studies of FDA-regulated products, 92 (63%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants enrolled in the treatment arm will receive a 6-month treatment with the JAK1/3 inhibitor tofacitinib to define the safety and efficacy of this medicine relative to placebo.
Drug: Tofacitinib Oral Solution
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
JAK1/3 inhibitor
Also known as: XELJANZ, Tofacitinib
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.
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.
Time frame: From screening to 1 month after end of treatment
Change in Kaufman Brief Intelligence Test, 2nd Edition Revised (KBIT-2 Revised) - Verbal Intelligence
Verbal Intelligence score, made up of the Verbal Knowledge and Riddles subtest, is a standardized measure of verbal cognitive ability. Raw scores,will be employed. Increase in scores indicate improvement in verbal cognitive performance.
Time frame: Baseline, 6 months
Change in Kaufman Brief Intelligence Test, 2nd Edition Revised (KBIT-2 Revised) - Nonverbal Intelligence
The KBIT-2 Revised Nonverbal Intelligence score is a standardized measure of nonverbal reasoning ability and is made up of the Matrices subtest. We will be using the raw score. Increase in scores indicate improvement in nonverbal cognitive performance.
Time frame: Baseline, 6 months
Change in Leiter 3 - Attention Sustained subtest
The Leiter-3 Attention Sustained subtest is a measure of inhibitory control. The raw score, calculated as the correct number of targets minus errors made across four trials, will be used. Increase in scores indicate improvement.
Time frame: Baseline, 6 months
Change in Vineland Adaptive Behavior Scales 3 (VABS-3) - Sum of Domain Raw Scores
The Vineland Adaptive Behavior Scales, Third Edition (VABS-3) assesses adaptive functioning across communication, daily living skills, socialization, and motor domains. Domain raw scores will be summed to produce a composite raw score. . Increase in scores indicate improvement in adaptive functioning.
Time frame: 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.
Time frame: Baseline, 6 months
Change in Peabody Picture Vocabulary Test, Fifth Edition (PPVT-5)
The Peabody Picture Vocabulary Test, Fifth Edition (PPVT-5) assesses receptive vocabulary. Growth Scale Values (GSV) are used to determine an individual's absolute progress over time and is sensitive to small changes . Increase in scores indicate improvement in receptive vocabulary ability. A Naturalistic Language Sample will be utilized to measure spontaneous expressive language. We will analyze total utterances and mean length of utterance. Increase in scores indicate improvement in expressive language skills
Time frame: Baseline, 6 months
Change in Naturalistic Language Sample
This measure evaluates spontaneous expressive language narration. We will analyze total utterances and mean length of utterance.
Time frame: Baseline, 6 months
Change in Developmental Behavior Checklist 2 (DBC-2) or Achenbach Child (or Adult) Behavior Checklist
The DBC-2 reports a statistically significant change in Developmental Behavioral Checklist-2 (DBC-2) T-scores within or between treatment arms. A decrease in score indicates improvement. Or the Achenbach is a caregiver-report measure of maladaptive behavior. This is a standardized questionnaire with available score norms by chronological age resulting in T-scores. We will analyze change in the internalizing and externalizing T-scores.
Time frame: Baseline, 6 months
Change in Social Responsiveness Scale 2 (SRS-2), School Age and Adult
The Social Responsiveness Scale, Second Edition (SRS-2) generates T-scores with a mean of 50 and a standard deviation of 10. . Increase in scores indicates greater severity of autism-related symptoms (worse outcome). Both total and social communication T-scores will be analyzed.
Time frame: Baseline, 6 months
Change in Modified Corsi Test
The Modified Corsi Test assesses working memory. Scores are summed based on total performance across all trials. Increase in scores indicates improvement in working memory performance.
Time frame: Baseline, 6 months
Change in Dimensional Change Card Sort test
The Dimensional Change Card Sort Test measures cognitive flexibility. The total number of correct post-switch responses will be calculated across the last two trials. Increase in scores indicates improvement in cognitive flexibility.
Time frame: Baseline, 6 months
Change in Beery Visual Motor Integration Scales (Beery VMI)
The Beery VMI, assesses visual-motor integration skills. Increase in scores indicates improvement in visual-motor integration ability.
Time frame: Baseline, 6 months
Change in Vineland Adaptive Behavior Scales, Third Edition (VABS-3) - Sum of Raw Scores
The Vineland-3 is composed of four domains: Communication, Daily Living Skills, Socialization, and Motor. Each domain score represents summed raw scores from subdomains. We will evaluate changes in the raw scores of the four domains.. Increase in scores indicate improvement of adaptive skills in communication, daily living skills, socialization, and motor skills.
Time frame: Baseline, 6 months
Change in Composite Neurodevelopmental Improvement Scores
This composite score aggregates standardized changes across multiple assessments. Individual measures are transformed into standardized differences before averaging. The composite score is not bounded by a fixed range. Higher values indicate greater overall improvement in neurodevelopmental functioning
Time frame: Baseline, 6 months
Change in Clinical Global Impression - Improvement in Neurodevelopment (CGI-I-ND)
This composite score aggregates standardized changes across multiple assessments. Individual measures are transformed into standardized differences before averaging. The composite score is not bounded by a fixed range. Higher values indicate greater overall improvement in neurodevelopmental functioning. CGI-I-ND is a scale to rate improvement.
Time frame: Baseline, 6 months
Change in Pediatric Quality of Life Inventory (PedsQL)
The Pediatric Quality of Life Inventory (PedsQL) produces scores ranging from 0 to 100. Scores indicate improvement in health-related quality of life.
Time frame: Baseline, 6 months
Plan to share: Yes — De-identified participant data will be made available for all primary outcome measures.
Supporting information: Study protocol, Informed consent form, 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.
No publications or documents are linked to this record.
Started May 2026 (actual). Primary completion is estimated for Aug 2030, 51 months after the start.
Of 21 phase 2 interventional studies under Down Syndrome, half reached primary completion within 36 months of starting (the median), counting those still running; a quarter within 26 and three quarters within 61. This study's planned 51 months is above that.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Tofacitinib
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