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

2026년 9월 4일 업데이트: Jonathan Santoro

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

연구 개요

상태

아직 모집하지 않음

정황

개입 / 치료

연구 유형

중재적

등록 (추정된)

20

단계

  • 2 단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 연락처 백업

연구 장소

  • 미국
    • California
      • Los Angeles, California, 미국, 90027
        • Children's Hospital Los Angeles
        • 연락하다:
        • 연락하다:
        • 수석 연구원:
          • Jonathan Santoro, MD

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 성인

건강한 자원 봉사자를 받아들입니다

아니

설명

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • 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.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 해당 없음
  • 중재 모델: 단일 그룹 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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.
의약품: 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.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Total AEs on Ublituximab
기간: 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.
Baseline through Week 24

2차 결과 측정

결과 측정
측정값 설명
기간
Change in Scores for Adaptive Behavior using VABS-3 Composite and Domain Survey
기간: Baseline, Week 12, and Week 24
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.
Baseline, Week 12, and Week 24
Change in Scores for Catatonia Severity using Bush-Francis Catatonia Rating Scale
기간: Baseline, Week 12, and Week 24

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)
Baseline, Week 12, and Week 24
Change in Score for Neuropsychiatric Symptoms using Neuropsychiatric Inventory Questionnaire (NPI-Q)
기간: Baseline, Week 12, and Week 24
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.
Baseline, Week 12, and Week 24
Change in Motor Function (Timed 25-Foot Walk)
기간: Baseline, Week 12, and Week 24
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.
Baseline, Week 12, and Week 24
Change in Global Clinical Status Using Clinician Global Impression of Change-Down Syndrome (CGIC-DS)
기간: Baseline, Week 12, and Week 24
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.
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)
기간: Baseline, Week 12, and Week 24
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. Lower CGI-S scores indicate reduced illness severity, and lower CGI-I scores indicate greater clinical improvement.
Baseline, Week 12, and Week 24
Change in Participant Quality of Life Using Pediatric Quality of Life Inventory (PedsQL) Parent Report
기간: Baseline, Week 12, and Week 24
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. Higher scores indicate better quality of life and functional status. Assessments will be conducted at Baseline, Week 12, and Week 24.
Baseline, Week 12, and Week 24
Change in Caregiver and Family Functioning Using Pediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM)
기간: Baseline to Week 24
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. 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.
Baseline to Week 24
Change in Communication Ability Using Observer-Reported Communication Ability (ORCA) Measure
기간: Baseline, Week 12, and Week 24
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. Higher scores indicate greater communication ability and improved functional communication.
Baseline, Week 12, and Week 24
Change in Caregiver and Family Functioning Using Pediatric Quality of Life Inventory Family Impact Module (PedsQL-FIM)
기간: Baseline, Week 12, and Week 24
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 activity, and family relationship domains. Higher scores indicate better caregiver and family functioning and lower family burden.
Baseline, Week 12, and Week 24
Change in Obsessive-Compulsive Symptom Severity Using Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS)
기간: Baseline, Week 12, and Week 24
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. Higher scores indicate greater obsessive-compulsive symptom severity, and decreases in total score indicate improvement.
Baseline, Week 12, and Week 24

기타 결과 측정

결과 측정
측정값 설명
기간
Change in Peripheral B-Cell Counts Following Ublituximab Treatment
기간: Baseline, Week 2, Week 6, Week 12, and Week 24
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.
Baseline, Week 2, Week 6, Week 12, and Week 24
Change in Inflammatory Cytokine Profiles
기간: Baseline and Week 24
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).
Baseline and Week 24
Change in Plasma Proteomic Signatures
기간: Baseline and Week 24
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.
Baseline and Week 24
Change in Plasma Metabolomic Profiles
기간: Baseline and Week 24
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.
Baseline and Week 24
Change in Interferon Signaling and Transcriptomic Profiles
기간: Baseline and Week 24
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.
Baseline and Week 24
Change in Global Autoantibody Profiles
기간: Baseline and Week 24
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
Baseline and Week 24
Change in Biomarkers of Neurodegeneration and Neuroinflammation
기간: Baseline and Week 24
Change from baseline in plasma biomarkers of neurodegeneration and neuroinflammation, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCHL1), total tau, and other validated biomarkers. Exploratory analyses will evaluate relationships between biomarker changes and clinical outcomes following ublituximab treatment.
Baseline and Week 24

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Jonathan Santoro

수사관

  • 수석 연구원: Jonathan Santoro, MD, Children's Hospital Los Angeles

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 10월 1일

기본 완료 (추정된)

2030년 10월 1일

연구 완료 (추정된)

2030년 12월 1일

연구 등록 날짜

최초 제출

2026년 9월 4일

QC 기준을 충족하는 최초 제출

2026년 9월 4일

처음 게시됨 (실제)

2026년 9월 10일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 9월 10일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 9월 4일

마지막으로 확인됨

2026년 9월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • CHLA-26-00158

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다