An Open-Label Phase II Feasibility Study for the Use of Ublituximab in Adults With Down Syndrome Regression Disorder

NCT07812181 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: CHLA-26-00158
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Down Syndrome Regression Disorder (DSRD); Down Syndrome (Trisomy 21); Neuroinflammatory / Neuropsychiatric Disorder

Keywords

Ublituximab; Down Syndrome Regression Disorder (DSRD); B-cell depletion

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline through Week 24

Secondary Outcomes (10)

• Change in Scores for Adaptive Behavior using Vineland Adaptive Behavior Scales, Third Edition (VABS-3) Composite and Domain Survey

  Baseline, Week 12, and Week 24

• Change in Scores for Catatonia Severity using Bush-Francis Catatonia Rating Scale (BFCRS)

  Baseline, Week 12, and Week 24

• Change in Score for Neuropsychiatric Symptoms using Neuropsychiatric Inventory Questionnaire (NPI-Q)

  Baseline, Week 12, and Week 24

• Change in Motor Function (Timed 25-Foot Walk)

  Baseline, Week 12, and Week 24

• Change in Global Clinical Status Using Clinician Global Impression of Change-Down Syndrome (CGIC-DS)

  Baseline, Week 12, and Week 24

Other Outcomes (10)

• Change in Peripheral B-Cell Counts Following Ublituximab Treatment

  Baseline, Week 2, Week 6, Week 12, and Week 24

• Change in Inflammatory Cytokine Profiles

  Baseline and Week 24

• Change in Plasma Proteomic Signatures

  Baseline and Week 24

Study Arms (1)

Ublituximab

EXPERIMENTAL

Participants 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.

Drug: Ublituximab

Interventions

Ublituximab DRUG

Participants 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.

Ublituximab

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Ability to attend all study visits with a study partner or legally authorized representative
• Study partner willing to comply with all study procedures
• Willingness to complete required washout periods for medications that may interfere with the study
• Highly effective contraception for reproductive participants and partners of childbearing potential.
• Study partner/LAR sufficiently proficient in English to complete assessments.

You may not qualify if:

• Mosaic Down syndrome
• Weight \< 40 kg at screening
• Pregnancy or breastfeeding
• Current or past tobacco smoking
• Poor venous access or inability to comply with IV procedures
• Use of IVIg within 8 weeks prior to baseline
• Use of immunosuppressive drugs within 12 weeks prior to baseline
• Prior treatment with anti-CD20 or B-cell therapies within required washout unless B-cell recovery criteria are met
• Other immunosuppressive biologics within 24 months.
• Any prior use of chemotherapeutic agents (e.g., methotrexate, cyclophosphamide)
• History of solid organ transplant
• Recent receipt of blood or plasma products (≤30 days)
• Clinically significant cardiac disease, clotting disorder, or other serious medical condition
• Active or chronic infection of clinical significance (including HBV, HCV, TB, HIV per protocol criteria)
• History of malignancy

Sponsors & Collaborators

• Jonathan Santoro: lead

Study Sites (1)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

MeSH Terms

Conditions

Down Syndrome

Interventions

ublituximab

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

• Jonathan Santoro, MD

  Children's Hospital Los Angeles

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mariam Yousuf

CONTACT

323-607-3505; dsresearch@chla.usc.edu

Samuel Otey

CONTACT

323-607-3505; dsresearch@chla.usc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Division of Neurology

Model Details: All participants are assigned to a single treatment arm and receive ublituximab. There is no comparator or control group, and outcomes are assessed longitudinally over 24 weeks.

Study Record Dates

• First Submitted: September 4, 2026
• First Posted: September 10, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: September 23, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)