A Phase 2 interventional study of Ublituximab in Down Syndrome Regression Disorder (DSRD), Down Syndrome (Trisomy 21) and Neuroinflammatory / Neuropsychiatric Disorder, sponsored by Jonathan Santoro. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years to 40 Years. Per ClinicalTrials.gov, last updated 2026-09-23.
Sponsored by Jonathan Santoro · Phase 2, Interventional, and Treatment
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:
This is a single-arm study, so there is no comparison group.
Participants will:
438 studies on the registry are indexed under Down Syndrome; 99 are open to participants now.
This study's planned enrollment of 20 is below the median of 37 across 286 interventional studies indexed under Down Syndrome.
Browse Down Syndrome studies →This is the only study on the registry with Jonathan Santoro as lead sponsor.
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:
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 line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
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.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
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.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
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.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
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.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
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.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
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
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.
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.
Time frame: Baseline through Week 24
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.
Time frame: 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)
Time frame: 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.
Time frame: 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.
Time frame: 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.
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)
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.
Time frame: 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.
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)
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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline, Week 12, and Week 24
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.
Time frame: Baseline, Week 2, Week 6, Week 12, and Week 24
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).
Time frame: Baseline and Week 24
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.
Time frame: Baseline and Week 24
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.
Time frame: Baseline and Week 24
Change in Interferon Signaling and Transcriptomic Profiles
Change from baseline in whole-blood transcriptomic signatures, including interferon-related gene expression profiles, measured from RNA biospecimens. Exploratory analyses will characterize molecular pathways associated with DSRD and assess the impact of B-cell depletion therapy on interferon signaling and other transcriptional biomarkers.
Time frame: Baseline and Week 24
Change in Global Autoantibody Profiles
Change from baseline in circulating autoantibody profiles measured using high-throughput autoantibody profiling technologies. Exploratory analyses will evaluate changes in autoantibody repertoires following ublituximab treatment and assess associations wi
Time frame: Baseline and Week 24
Change in Neurofilament Light Chain (NfL)
Change from baseline in plasma biomarker of neurodegeneration and neuroinflammation, neurofilament light chain (NfL). Exploratory analyses will evaluate relationships between biomarker changes and clinical outcomes following ublituximab treatment.
Time frame: Baseline and Week 24
Change in Glial Fibrillary Acidic Protein (GFAP)
Change from baseline in plasma biomarker of neurodegeneration and neuroinflammation, glial fibrillary acidic protein (GFAP). Exploratory analyses will evaluate relationships between biomarker changes and clinical outcomes following ublituximab treatment.
Time frame: Baseline and Week 24
Change in Ubiquitin C-terminal Hydrolase L1 (UCHL1)
Change from baseline in plasma biomarker of neurodegeneration and neuroinflammation, ubiquitin C-terminal hydrolase L1 (UCHL1). Exploratory analyses will evaluate relationships between biomarker changes and clinical outcomes following ublituximab treatment.
Time frame: Baseline and Week 24
Change in Total Tau
Change from baseline in plasma biomarker of neurodegeneration and neuroinflammation, total tau. Exploratory analyses will evaluate relationships between biomarker changes and clinical outcomes following ublituximab treatment.
Time frame: Baseline and Week 24
Plan to share: No
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Start is estimated for Oct 2026; primary completion for Oct 2030, 48 months later.
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 48 months is above that.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Ublituximab