The goal of this clinical trial is to evaluate whether the monoclonal antibody ublituximab can treat Down Syndrome Regression Disorder (DSRD) by assessing its safety, tolerability, and preliminary efficacy in affected individuals. This study is conducted in adults aged 18-40 years with Down syndrome who have DSRD and have had an inadequate or partial response to first-line therapies.
The main questions it aims to answer are:
* Does ublituximab demonstrate acceptable safety and tolerability, as measured by treatment-emergent adverse events from baseline through Week 24? * Does ublituximab lead to improvement in cognitive, neuropsychiatric, motor, and functional outcomes from baseline to Weeks 12 and 24?
This is a single-arm study, so there is no comparison group.
Participants will:
* Receive two intravenous infusions of ublituximab (150 mg on Day 1 and 450 mg on Day 15) * Attend study visits at Screening, Baseline (Day 1) , Week 2 (Day 15), Week 3, Week 6, Week 12, and Week 24 * Undergo clinical assessments, including neurological and physical exams and safety monitoring labs throughout the study * Complete cognitive, behavioral, and functional evaluations at Baseline, Week 12, and Week 24 * Provide blood samples for safety monitoring and research biomarker analyses
Age 18 to 40 years, inclusive at time of consent
Diagnosis of Down syndrome (trisomy 21 or translocation type)
Diagnosis of possible or probable Down Syndrome Regression Disorder (DSRD) based on 2022 International Consensus Criteria
History of partial response or non-response to first-line treatment (e.g., lorazepam, SSRIs, corticosteroids, and/or IVIg). Partial response = 10-50% improvement, Non-response = <10% improvement, Based on BFCRS or NPI-Q after 3 months of treatment.
Mosaic Down syndrome
Weight < 40 kg at screening
Pregnancy or breastfeeding
Current or past tobacco smoking
Single group
Ublituximab
DrugParticipants assigned to the Ublituximab arm will receive a fixed two-dose intravenous regimen consisting of 150 mg on Day 1 and 450 mg on Day 15. All participants will be followed for 24 weeks with regular safety monitoring, clinical assessments, and evaluation of cognitive, neuropsychiatric, and functional outcomes.
Total AEs on Ublituximab
Safety will be evaluated by the incidence, type, severity (graded per CTCAE v5.0), and relationship of treatment-emergent adverse events (AEs) occurring after the first dose of ublituximab. Tolerability will be assessed by the proportion of participants completing both doses and follow-up without dose modifications, interruptions, or discontinuation due to AEs.
Change in Scores for Adaptive Behavior using Vineland Adaptive Behavior Scales, Third Edition (VABS-3) Composite and Domain Survey
Change from baseline in adaptive functioning measured by the Vineland Adaptive Behavior Scales, Third Edition (VABS-3), including communication, daily living skills, socialization, and maladaptive behavior domains as reported by caregivers. The VABS-3 composite score ranges from 20 to 140, with lower scores indicating more significant adaptive deficits, and higher scores indicating better adaptive functioning and a better outcome.
Change in Scores for Catatonia Severity using Bush-Francis Catatonia Rating Scale (BFCRS)
Change from baseline in catatonia symptoms measured by the Bush-Francis Catatonia Rating Scale (BFCRS), with decreases in total score indicating improvement in symptom severity. 0 (no catatonia) - 45 (Severe Catatonia)
Change in Score for Neuropsychiatric Symptoms using Neuropsychiatric Inventory Questionnaire (NPI-Q)
Change from baseline in neuropsychiatric symptom burden as measured by the Neuropsychiatric Inventory Questionnaire (NPI-Q), a caregiver-reported assessment of symptom frequency and severity across behavioral domains. The NPI-Q severity score ranges from a minimum of 0 to a maximum of 36, with higher scores indicated greater symptom severity. The NPI-Q caregiver distress score ranges from a minimum of 0 to a maximum of 60, with higher scores indicating greater caregiver distress.
Change in Motor Function (Timed 25-Foot Walk)
Change from baseline in time (seconds) required to complete the Timed 25-Foot Walk (T25-FW), reflecting gait speed and motor function, with decreased time indicating improvement. There are no minimum or maximum scores for the T25-FW as the value reported is a unit of time to the nearest tenth of a second.
Change in Peripheral B-Cell Counts Following Ublituximab Treatment
Change from baseline in peripheral B-cell populations measured by high-sensitivity flow cytometry, including absolute B-cell counts and percentages of CD19+ and CD20+ B cells. Exploratory analyses will evaluate the extent and duration of B-cell depletion following ublituximab treatment and the association between B-cell depletion and clinical outcomes.
Change in Inflammatory Cytokine Profiles
Change from baseline in circulating inflammatory cytokine concentrations measured using multiplex immunoassay platforms. Cytokines and related inflammatory biomarkers will be evaluated to characterize immunologic changes associated with ublituximab treatment and Down Syndrome Regression Disorder (DSRD).
Change in Plasma Proteomic Signatures
Change from baseline in plasma proteomic profiles measured using high-throughput proteomic platforms. Exploratory analyses will identify protein expression patterns associated with DSRD and evaluate molecular changes occurring following ublituximab treatment.
Change in Plasma Metabolomic Profiles
Change from baseline in plasma metabolomic signatures measured using mass spectrometry-based metabolomic analyses. Exploratory analyses will evaluate treatment-associated changes in metabolic pathways and identify biomarkers associated with disease activity and therapeutic response.
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Jonathan Santoro
Lead sponsor
Children's Hospital Los Angeles
Sponsor institution
This trial is not recruiting at the moment. You can still explore other options:
