Down Syndrome Regression Disorder (DSRD)Phase 2NCT07812181
An Open-Label Phase II Feasibility Study for the Use of Ublituximab in Adults With Down Syndrome Regression Disorder
A Phase 2 study testing Ublituximab in people with Down Syndrome Regression Disorder (DSRD) and Down Syndrome (Trisomy 21), run by Jonathan Santoro at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years
- Conditions the study is for
- Down Syndrome Regression Disorder (DSRD), Down Syndrome (Trisomy 21), Neuroinflammatory / Neuropsychiatric Disorder
- What is being tested?
- Ublituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2026to 1 Dec 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
- Abnormal screening labs indicating unacceptable risk
- Receipt of live or live-attenuated vaccines within 4 weeks prior to treatment
- Untreated thyroid disease (hypo- or hyperthyroidism)
- History of moyamoya syndrome or stroke
- Wards of the state
- Employees or students of Children's Hospital Los Angeles (CHLA)
- Prior neurosurgical intervention (exceptions for longstanding shunts)
- Current investigational therapy/prohibited medications
- Detailed HBV, HCV, and TB criteria
- Requirement for B-cell recovery >50 cells/μL after prior anti-CD20 therapy.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Children's Hospital Los Angeles
Los Angeles, California, 90027
Mariam Yousuf, 323-607-3505, dsresearch@chla.usc.edu
Samuel Otey, 323-607-3505, dsresearch@chla.usc.edu
About this study
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:
Read more
- 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
- Being tested
- Ublituximab
- Keywords
- Ublituximab, Down Syndrome Regression Disorder (DSRD), B-cell depletion
- Medical subject headings
- Down Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UblituximabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Ublituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: Baseline, Week 12, and Week 24
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)
Measured: Baseline, Week 12, and Week 24
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.
Measured: Baseline, Week 12, and Week 24
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.
Measured: Baseline, Week 12, and Week 24
Change in Global Clinical Status Using Clinician Global Impression of Change-Down Syndrome (CGIC-DS)
Change from baseline in global clinical status assessed using the Clinician Global Impression of Change-Down Syndrome (CGIC-DS), a Down syndrome-adapted clinician-rated instrument. The Baseline version generates a Clinical Global Impression-Severity (CGI-S) rating to assess overall illness severity, and the Follow-up version generates a Clinical Global Impression-Improvement (CGI-I) rating to assess clinical change relative to baseline. CGI-S scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill), while CGI-I scores range from 1 (very much improved) to 7 (very much worse). Assessments will be conducted at Baseline, Week 12, and Week 24.
Measured: Baseline, Week 12, and Week 24
Change in Global Clinical Status Using Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) Scores Derived from the Clinician Global Impression of Change-Down Syndrome (CGIC-DS)
Change from baseline in global clinical status measured using CGI-S and CGI-I ratings derived from the Clinician Global Impression of Change-Down Syndrome (CGIC-DS). CGI-S assesses overall illness severity, and CGI-I assesses improvement or worsening relative to baseline. Assessments will be conducted at Baseline, Week 12, and Week 24. CGI-S scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill), while CGI-I scores range from 1 (very much improved) to 7 (very much worse). Lower CGI-S scores indicate reduced illness severity, and lower CGI-I scores indicate greater clinical improvement.
Measured: Baseline, Week 12, and Week 24
Change in Participant Quality of Life Using Pediatric Quality of Life Inventory (PedsQL) Parent Report
Change from baseline in participant quality of life measured by the Pediatric Quality of Life Inventory (PedsQL) Parent Report. This caregiver-reported assessment evaluates health-related quality of life across physical functioning, emotional functioning, social functioning, and work/studies functioning domains. The PedsQL report has a minimum score of 0 and a maximum score of 100. Higher scores indicate better quality of life and functional status. Assessments will be conducted at Baseline, Week 12, and Week 24.
Measured: Baseline, Week 12, and Week 24
Change in Caregiver and Family Functioning Using Pediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM)
Change from baseline in caregiver and family functioning measured by the Pediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM). This caregiver-reported assessment evaluates the impact of the participant's condition on caregiver well-being and family functioning across physical, emotional, social, cognitive, communication, daily activities, and family relationship domains. The PedsQL-FIM has a minimum score of 0 and a maximum score of 100. Higher scores indicate better caregiver quality of life, improved family functioning, and less negative impact on the family. Assessments will be conducted at Baseline, Week 12, and Week 24.
Measured: Baseline to Week 24
Change in Communication Ability Using Observer-Reported Communication Ability (ORCA) Measure
Change from baseline in communication abilities measured by the Observer-Reported Communication Ability (ORCA) Measure, a caregiver-reported assessment of expressive and receptive communication skills. The ORCA evaluates verbal communication, use of gestures, social communication, requesting, conversation, comprehension, and functional communication abilities in everyday settings. The ORCA measure uses standardized T-scores ranging from a minimum of 25.8 and a maximum of 83.8. Higher T-scores indicate greater communication ability and improved functional communication.
Measured: Baseline, Week 12, and Week 24
Change in Obsessive-Compulsive Symptom Severity Using Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS)
Change from baseline in obsessive-compulsive symptom severity measured by the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), a clinician-administered assessment of obsessions and compulsions. The CY-BOCS evaluates symptom severity across domains including time occupied, interference, distress, resistance, and degree of control. Scores on the CY-BOSC range from a minimum of 0 and a maximum of 40. Higher scores indicate greater obsessive-compulsive symptom severity, and decreases in total score indicate improvement.
Measured: Baseline, Week 12, and Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2026
- Study start1 Oct 2026 (estimated)
- Primary completion1 Oct 2030 (estimated)
- Study completion1 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Down Syndrome Regression Disorder (DSRD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jonathan Santoro
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jonathan Santoro, Children's Hospital Los Angeles
- Investigators
- Jonathan Santoro, MD, Principal investigator, Children's Hospital Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07812181
- Sponsor's protocol ID
- CHLA-26-00158
- Status last verified
- Sep 2026
- First submitted
- 4 Sep 2026
- Last updated
- 23 Sep 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Phase II Feasibility Study for the Use of Ublituximab in Adults With Down Syndrome Regression Disorder
- ClinicalTrials.gov ID
- NCT07812181
- Acronym / sponsor ID
- CHLA-26-00158
- Conditions
- Down Syndrome Regression Disorder (DSRD), Down Syndrome (Trisomy 21), Neuroinflammatory / Neuropsychiatric Disorder
- Keywords
- Ublituximab, Down Syndrome Regression Disorder (DSRD), B-cell depletion
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Jonathan SantoroUniversity, hospital or other
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 1 Oct 2030 (estimated)
- Study completion
- 1 Dec 2030 (estimated)
- First posted
- 10 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Ublituximab | Experimental | Drug: UblituximabParticipants 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. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UblituximabParticipants 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 |
Primary outcome
Total AEs on Ublituximab
Time frame: Baseline through Week 24
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.
10 secondary outcomes
Change in Scores for Adaptive Behavior using Vineland Adaptive Behavior Scales, Third Edition (VABS-3) Composite and Domain Survey
Time frame: Baseline, Week 12, and Week 24
Change in Scores for Catatonia Severity using Bush-Francis Catatonia Rating Scale (BFCRS)
Time frame: Baseline, Week 12, and Week 24
Change in Score for Neuropsychiatric Symptoms using Neuropsychiatric Inventory Questionnaire (NPI-Q)
Time frame: Baseline, Week 12, and Week 24
Change in Motor Function (Timed 25-Foot Walk)
Time frame: Baseline, Week 12, and Week 24
Change in Global Clinical Status Using Clinician Global Impression of Change-Down Syndrome (CGIC-DS)
Time frame: Baseline, Week 12, and Week 24
Change in Global Clinical Status Using Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) Scores Derived from the Clinician Global Impression of Change-Down Syndrome (CGIC-DS)
Time frame: Baseline, Week 12, and Week 24
Change in Participant Quality of Life Using Pediatric Quality of Life Inventory (PedsQL) Parent Report
Time frame: Baseline, Week 12, and Week 24
Change in Caregiver and Family Functioning Using Pediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM)
Time frame: Baseline to Week 24
Change in Communication Ability Using Observer-Reported Communication Ability (ORCA) Measure
Time frame: Baseline, Week 12, and Week 24
Change in Obsessive-Compulsive Symptom Severity Using Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS)
Time frame: Baseline, Week 12, and Week 24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2026.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jonathan Santoro, MD principal investigator
Children's Hospital Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ublituximab in people with Down Syndrome Regression Disorder (DSRD) and Down Syndrome (Trisomy 21), run by Jonathan Santoro at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mariam Yousuf (323-607-3505, dsresearch@chla.usc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total AEs on Ublituximab (time frame: Baseline through Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Sep 2026.