TB006 for Autism Spectrum Disorder

Официальное название

A Multi-center Double Blind Placebo Controlled Study to Assess the Safety and Efficacy of TB006 for Improving Core Symptoms in Adults With Autism Spectrum Disorder

Обзор

Multisite 14-week prospective double-blind placebo controlled parallel-group randomized clinical trial with 14-week open-label extension at the end of double-blind treatment phase for placebo subjects. Eligible subjects will be randomized within each site in 2:1 ratio to receive either TB006 or placebo treatment.

Подробное описание

A key molecular mechanism implicated in ASD is immune dysregulation and unchecked neuroinflammation marked by increased microglial activation. Galectin-3 (Gal-3), a galactoside-binding lectin, is critical to activation of neuroinflammation resulting in the proliferation of microglia.7 Gal-3 has been shown to be elevated in individuals with ASD. To inhibit Gal-3's contribution to neuroinflammation, Truebinding has developed TB006, a neutralizing monoclonal antibody against Gal-3. Our overall hypothesis is that TB006 will significantly improve core and associated behavioral symptoms of ASD and be well tolerated with no significant adverse effects in adults with ASD.

Вмешательства

• Препарат TB006
  TB006 is a humanized immunoglobulin G4 (IgG4) (S228P) type monoclonal antibody that is highly specific and has a high affinity to human Galectin-3 (hGal-3).

Первичные конечные точки

• Childhood Autism Rating Scores (CARS) [Срок оценки: Baseline, Week 8 and Week 14]

Вторичные конечные точки (7)

• NIH Toolbox [Срок оценки: Baseline and Week 14]
• Clinical Global Impression Scale (CGI) [Срок оценки: Baseline, Week 8 and Week 14]
• Social Responsiveness Scale (SRS) [Срок оценки: Baseline, Week 8, Week 12 and Week 14]
• Aberrant Behavior Checklist (ABC) [Срок оценки: Screening, Weeks 4, 8, 12 and 14]
• Major Parental Concerns [Срок оценки: Baseline, Week 8, Week 12 and Week 14]
• Ohio State University Clinical Impressions Scale [Срок оценки: Baseline and Week 14]
• Vineland Adaptive Behavior Scale [Срок оценки: Baseline, Week 8 and Week 14]

Критерии участия

Критерии включения

• Autism Spectrum Disorder as defined below by the ADOS or ADI-R.
• Between 18 and 35 years of age at baseline.
• English included in the languages in which the individual is being raised.
• Autism severity of moderate or higher (≥4) under the 7-item clinical global impression-severity scale.
• Ability to maintain all ongoing complementary, dietary, traditional, and behavioral treatments constant for the study period.
• Unchanged complementary, dietary, traditional, and behavioral treatments for two months prior to study entry.
• In males and females of childbearing age, two forms of birth control must be used unless they are not sexually active.
• A caretaker who will accompany the patient to all procedures and has adequate contact with the participant to complete caregiver questionnaires.

Критерии исключения

• LGALS3 rs4644 single nucleotide polymorphism with two copies of the Variant-type allele.
• History of infusion reactions to immunoglobulin product.
• Significant self-abusive or violent behavior or evidence of suicidal ideation, plan or behavior.
• Severely affected as defined by CGI-Severity Standard Score = 7 (Extremely Ill).
• Severe prematurity (<34 weeks gestation) as determined by medical history.
• Current uncontrolled gastroesophageal disorders.
• Current or history of liver or kidney disease as determined by medical history and safety labs (See Laboratory Values Monitoring Plan for specific laboratory values).
• Genetic syndromes.
• Congenital brain malformations.
• Active Epilepsy Diagnosis (Epilepsy Diagnosis is defined as History of two or more unprovoked seizures; Patient with a history of epilepsy who have been off medication without seizures for more than two years do not qualify as active epilepsy).
• Any medical condition that the PI determines could jeopardize the safety of the study subject or compromise the integrity of the data.
• Significant negative reaction (i.e., fainting, vomiting, etc.) because of a previous blood draw.
• Failure to thrive or < 5%ile for Body Mass Index or weight at the time of screening.
• Concurrent treatment with drug that would significantly interact with the investigational product.
• Allergy or Sensitivity to ingredients in the investigational product or placebo.
• Evaluation with the NIH Toolbox or BOSCC within 3 months of entering the study.
• Planned evaluation with the NIH Toolbox or BOSCC during the study.
• Pregnancy
• Current DSM-5 diagnosis requiring alternative pharmacotherapy, e.g., Major Depression, Bipolar Disorder, a psychotic disorder (based on clinical assessment assisted by the Child and Adolescent Symptom Inventory).
• Refusal to comply with the use of birth control if sexually active.
• Abnormal vital signs (systolic blood pressure > 180 mmHg or < 90 mmHg; heart rate > 120 beats per minute or < 55 beats per minute; temperature > 101.0o F; oxygen saturation < 90%)
• Prolonged QTc (defined as > 450ms for males and >470ms for female) or any abnormalities felt by the investigator to be of concern.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Rossignol Medical Center — Phoenix
• Rossignol Medical Center — Aliso Viejo

Публикации

• Rodriguez JI, Kern JK. Evidence of microglial activation in autism and its possible role in brain underconnectivity. Neuron Glia Biol. 2011 May;7(2-4):205-13. doi: 10.1017/S1740925X12000142. Epub 2012 Jul 6. PMID 22874006
• Garcia-Revilla J, Boza-Serrano A, Espinosa-Oliva AM, Soto MS, Deierborg T, Ruiz R, de Pablos RM, Burguillos MA, Venero JL. Galectin-3, a rising star in modulating microglia activation under conditions of neurodegeneration. Cell Death Dis. 2022 Jul 20;13(7):628. doi: 10.1038/s41419-022-05058-3. PMID 35859075
• Wang X, Zhang S, Lin F, Chu W, Yue S. Elevated Galectin-3 Levels in the Serum of Patients With Alzheimer's Disease. Am J Alzheimers Dis Other Demen. 2015 Dec;30(8):729-32. doi: 10.1177/1533317513495107. Epub 2013 Jul 2. PMID 23823143
• Artik A, Kocaman O, Kara H, Tuncer SC. Galectin-3 levels in school aged children with autism spectrum disorder. Int J Dev Disabil. 2022 Dec 1;69(5):757-761. doi: 10.1080/20473869.2022.2150035. eCollection 2023. PMID 37547549

Идентификаторы

NCT: NCT06500637 · TB-RMC

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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