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

ConditionDown Syndrome

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age6-22

SponsorUniversity of Colorado, Denver

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

Tofacitinib Oral Solution
Drug
JAK1/3 inhibitor
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.

Treatment groups

92 Participants

are divided into 2 treatment groups

Group A: Treatment ArmExperimental treatment 1 intervention

Group B: Placebo armPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

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

Secondary outcomes

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

Other outcomes

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

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Colorado, Denver

Lead sponsor

Anschutz Acceleration Initiative

Collaborator

GLOBAL Down Syndrome Foundation

Collaborator

Source ClinicalTrials.gov

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