TB006 for Autism Spectrum Disorder

Official title

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

Overview

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.

Detailed description

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.

Interventions

• Drug 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).

Primary outcome measures

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

Secondary outcome measures (7)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 2 centers

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

Publications

• 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

Identifiers

NCT: NCT06500637 · TB-RMC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗