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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 2
- 主要终点
- Childhood Autism Rating Scores (CARS)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
- •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.
研究组 & 干预措施
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). Galectins are a ubiquitous group of proteins found in a variety of cells, tissues, and extravascular spaces, and are involved in numerous metabolic processes and functions. The galectins preferentially bind to β-galactoside derivatives and can cross-link surface glycoproteins by binding galactose residues. The Gal-3 protein plays an important role in different pathogenic conditions, including neurodegenerative and neuroinflammatory disorders. Serum levels of Gal-3 have been found to be elevated in ASD.
干预措施: TB006 (Drug)
Placebo
Identical IV solution without TB006 product
干预措施: TB006 (Drug)
结局指标
主要结局
Childhood Autism Rating Scores (CARS)
时间窗: Baseline, Week 8 and Week 14
The CARS is a measure of autism severity completed by a clinician. Lower Score is Better. Scores range from 15 to 60.
次要结局
- Clinical Global Impression Scale (CGI)(Baseline, Week 8 and Week 14)
- NIH Toolbox(Baseline and Week 14)
- Aberrant Behavior Checklist (ABC)(Screening, Weeks 4, 8, 12 and 14)
- Vineland Adaptive Behavior Scale(Baseline, Week 8 and Week 14)
- Social Responsiveness Scale (SRS)(Baseline, Week 8, Week 12 and Week 14)
- Major Parental Concerns(Baseline, Week 8, Week 12 and Week 14)
- Ohio State University Clinical Impressions Scale(Baseline and Week 14)