TB006 for Autism

Recruiting at 1 trial location

Overseen By Richard E Frye, M.D., PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Rossignol Medical Center

Disqualifiers: Epilepsy, Liver disease, Kidney disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 14 weeks

45 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you must keep any complementary, dietary, traditional, and behavioral treatments unchanged for two months before and during the study.

What data supports the idea that TB006 for Autism is an effective treatment?

The available research does not provide any data on the effectiveness of TB006 for Autism. All the studies mentioned focus on treatments for multiple sclerosis, a different condition. Therefore, there is no information here to support the idea that TB006 is an effective treatment for Autism. ^{1 2 3 4 5}

What safety data exists for TB006 in autism treatment?

The provided research does not mention TB006 specifically. However, it discusses the safety of aripiprazole, a medication used for irritability in autism. In a 52-week study, 58.62% of participants experienced treatment-emergent adverse events, with the most common being nasopharyngitis and weight increase. Serious adverse events occurred in 5.17% of participants but were not considered adverse drug reactions. The study concluded that aripiprazole was well tolerated. No specific safety data for TB006 is available in the provided research. ^{6 7 8 9 10}

Is the drug TB006 a promising treatment for autism?

Yes, TB006 is a promising treatment for autism because it targets IL-6, a factor linked to autism-like behaviors. By addressing IL-6, TB006 could help improve social interactions and reduce anxiety and learning difficulties in individuals with autism. ^{11 12 13 14 15}

Research Team

Richard E Frye, M.D., Ph.D

Principal Investigator

Rossignol Medical Center

Daniel A Rossignol, MD

Principal Investigator

Rossignol Medical Center

Eligibility Criteria

This trial is for individuals with Autism Spectrum Disorder. Participants should be able to attend multiple site visits over a 14-week period and are willing to potentially continue in an open-label extension phase.

Inclusion Criteria

English included in the languages in which the individual is being raised

I haven't changed my non-medical treatments in the last 2 months.

A caretaker who will accompany the patient to all procedures and has adequate contact with the participant to complete caregiver questionnaires

Exclusion Criteria

Any medical condition that the PI determines could jeopardize the safety of the study subject or compromise the integrity of the data

Congenital brain malformations

I have a diagnosed genetic syndrome.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive TB006 or placebo treatment in a double-blind manner

14 weeks

Multiple visits (in-person)

Open-label extension

Placebo subjects receive TB006 treatment in an open-label manner

14 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• TB006

Trial Overview The study tests TB006's effectiveness compared to a placebo in treating Autism Spectrum Disorders. It's designed as a double-blind, meaning neither the participants nor the researchers know who gets what treatment until after the results are collected.

Participant Groups

Group I: TB006 Experimental Treatment 1 Intervention

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.

Group II: Placebo Placebo Group 1 Intervention

Identical IV solution without TB006 product

Who Is Running the Clinical Trial?

Rossignol Medical Center

Lead Sponsor

Trials

6

Recruited

780+

Autism Discovery and Treatment Foundation

Collaborator

Trials

2

Recruited

1,000+

Findings from Research

The study evaluated the effectiveness of an electronic monitoring device combined with behavioral feedback to improve adherence to multiple sclerosis therapies in young patients.

The trial was randomized, indicating a robust design to assess the impact of these interventions on treatment adherence, although specific results and participant numbers are not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correction to: Impact of an electronic monitoring device and behavioural feedback on adherence to multiple sclerosis therapies in youth: results of a randomized trial. Yeh, EA., Grover, SA., Powell, VE., et al.[2019]

Over the past 40 years, significant advancements in neuroimmunology have led to the development of effective disease-modifying therapies (DMTs) for multiple sclerosis (MS), improving patient outcomes and reducing disease burden.

Enhanced diagnostic criteria, disability assessment scales, imaging techniques, and biomarkers have contributed to a deeper understanding of MS, paving the way for more targeted and effective treatments in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials in multiple sclerosis: past, present, and future. Manouchehri, N., Shirani, A., Salinas, VH., et al.[2022]

Ofatumumab, an anti-CD20 monoclonal antibody approved for relapsing multiple sclerosis, was prescribed to 2,101 patients in a study that highlighted its increasing use as a first-line disease-modifying therapy, particularly among DMT-naïve patients, who made up a growing percentage of users over time.

The study found that the majority of patients were middle-aged women with mild MS symptoms, and many patients aged 55 and older were also treated with ofatumumab, suggesting a growing confidence in its safety and effectiveness beyond the initial trial population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world use of ofatumumab to treat multiple sclerosis 9 months post-FDA approval during COVID-19 pandemic. Coyle, PK., Gorritz, M., Wade, RL., et al.[2023]

A systematic review of 226 randomized controlled trials (RCTs) on disease-modifying therapies (DMT) for relapsing forms of multiple sclerosis (RMS) revealed that 89% reported clinical efficacy outcomes, highlighting the importance of these measures in evaluating treatment effectiveness.

The study identified significant variability in the definitions of clinical outcomes, with 77 different outcomes and 36 definitions for 'relapse', indicating a need for standardized measures to improve consistency in future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy outcomes reported in trials of multiple sclerosis: A systematic scoping review. Oliveira, ML., Lucchetta, RC., Bonetti, AF., et al.[2021]

In a study involving 1000 patients with relapsing forms of multiple sclerosis, switching to teriflunomide from other disease-modifying therapies significantly increased treatment satisfaction scores across various reasons for switching, indicating a positive impact on patient experience.

Patients who switched to teriflunomide also showed stability or improvement in measures of disability, cognition, and quality of life, while the safety profile remained consistent with previous clinical trials, suggesting that teriflunomide is a well-tolerated option for MS treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in patients with relapsing forms of MS switching to teriflunomide from other disease-modifying therapies: Results from the global Phase 4 Teri-PRO study in routine clinical practice. Coyle, PK., Khatri, B., Edwards, KR., et al.[2021]

In a 52-week study involving 58 Asian children and adolescents with autistic disorder, aripiprazole significantly improved behavioral issues and adaptive functioning, as measured by various scales including the Aberrant Behavior Checklist and Clinical Global Impression scale.

While 58.62% of participants experienced treatment-emergent adverse events, the most common were mild (nasopharyngitis and weight gain), and serious adverse events were rare, indicating that aripiprazole is generally well tolerated over long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Improvement and Safety of Aripiprazole for Irritability and Adaptive Function in Asian Children and Adolescents with Autistic Disorder: A 52-Week, Multinational, Multicenter, Open-Label Study. Kim, BU., Kim, HW., Park, EJ., et al.[2022]

A study involving 71 adults with autism spectrum disorder (ASD) found that genotyping the CYP2D6 enzyme can help predict drug tolerability and prevent adverse reactions to medications like risperidone and aripiprazole.

Participants with the intermediate (IM) CYP2D6 phenotype experienced the highest rates of neurological and psychiatric adverse events, especially when taking multiple medications, highlighting the importance of personalized medicine in managing ASD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CYP2D6 Genotype and Pharmacovigilance Impact on Autism Spectrum Disorder: A Naturalistic Study with Extreme Phenotype Analysis. Ballester, P., Espadas, C., Almenara, S., et al.[2023]

Several treatments for autism spectrum disorders (ASD) have been identified, with melatonin, acetylcholinesterase inhibitors, naltrexone, and music therapy receiving a 'Grade A' recommendation, indicating strong support from clinical trials.

Despite the promising nature of these treatments, all are currently considered off-label for ASD, highlighting the need for further research and the importance of physicians discussing unconventional treatments with their patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel and emerging treatments for autism spectrum disorders: a systematic review. Rossignol, DA.[2018]

Adults with autism spectrum disorders (ASD) have significantly higher rates of prescription drug use and polypharmacy compared to adults without ASD, with nearly 75% of those with ASD having over 20 prescription drug claims annually.

The study found that 85% of adults with ASD used at least one psychotropic medication, with common prescriptions including antipsychotics and anticonvulsants, highlighting the need for careful monitoring of treatment efficacy and safety due to the high rates of polypharmacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescription Drug Use and Polypharmacy Among Medicaid-Enrolled Adults with Autism: A Retrospective Cross-Sectional Analysis. Vohra, R., Madhavan, S., Sambamoorthi, U., et al.[2020]

In a long-term study involving 86 pediatric patients with autistic disorder, aripiprazole was found to be generally safe and well-tolerated, with most side effects being mild or moderate, such as nasopharyngitis and somnolence.

After 48 weeks of treatment, aripiprazole significantly reduced irritability symptoms, with a mean change of -6.3 in patients previously on placebo, indicating its efficacy in managing irritability associated with autism spectrum disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label extension long-term study of the safety and efficacy of aripiprazole for irritability in children and adolescents with autistic disorder in Japan. Ichikawa, H., Hiratani, M., Yasuhara, A., et al.[2019]

Systemic treatment with IL-6 receptor antibodies (IL-6R ab) significantly reduced the development and frequency of seizures in Synapsin 2 knockout (Syn2 KO) mice when administered before the onset of seizures, indicating a potential therapeutic window for intervention.

However, early IL-6R ab treatment did not reverse neuroinflammatory changes or improve behavioral aspects related to autism spectrum disorder, suggesting that while IL-6 signaling is involved in epilepsy development, it may not directly influence cognitive or mood-related symptoms in this model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced epilepsy development in synapsin 2 knockout mice with autistic behavior following early systemic treatment with interleukin-6 receptor antibody. Bäckström, F., Ahl, M., Wickham, J., et al.[2023]

The prevalence of Autism Spectrum Disorder (ASD) has increased to about 1 in 36 children, with various hereditary and environmental factors linked to a higher risk of developing the condition.

Both pharmacological treatments (like atypical antipsychotics and antidepressants) and non-pharmacological interventions (such as cognitive behavioral therapy and music therapy) are available for managing ASD symptoms, with ongoing research into novel therapies for more effective long-term solutions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autism Spectrum Disorder: Classification, diagnosis and therapy. Sharma, SR., Gonda, X., Tarazi, FI.[2022]

In Stockholm, Sweden, the prevalence of diagnosed autism spectrum disorders (ASD) in 2011 was found to be 0.40% in children aged 0-5 years and increased to 1.76% in young adults aged 18-27, indicating a significant rise in diagnoses across age groups.

Between 2001 and 2011, the prevalence of ASD among children aged 2-17 years increased nearly 3.5 times, primarily due to an eightfold rise in cases of ASD without intellectual disability, suggesting that factors like improved awareness and diagnostic practices may have contributed to this increase.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in prevalence of autism spectrum disorders in 2001-2011: findings from the Stockholm youth cohort. Idring, S., Lundberg, M., Sturm, H., et al.[2022]

Emerging evidence suggests that elevated levels of interleukin (IL)-6 in the brain, potentially due to activated glia or maternal immune activation, may contribute to autism-like behaviors by affecting brain structure and neuronal plasticity.

This review highlights the potential of targeting IL-6 as a pharmacological intervention for autism, indicating that further research could be significant in developing new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain IL-6 and autism. Wei, H., Alberts, I., Li, X.[2013]

Mice with elevated levels of IL-6 in the brain exhibited several behaviors associated with autism, such as cognitive impairments, anxiety, and reduced social interactions, indicating a potential link between IL-6 and autistic features.

The study suggests that elevated IL-6 may disrupt the balance of excitatory and inhibitory synaptic transmissions and alter dendritic spine structures, which could contribute to the development of autism-like behaviors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors. Wei, H., Chadman, KK., McCloskey, DP., et al.[2016]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Correction to: Impact of an electronic monitoring device and behavioural feedback on adherence to multiple sclerosis therapies in youth: results of a randomized trial. [2019]

2. Poland pubmed.ncbi.nlm.nih.gov

Clinical trials in multiple sclerosis: past, present, and future. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Real-world use of ofatumumab to treat multiple sclerosis 9 months post-FDA approval during COVID-19 pandemic. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy outcomes reported in trials of multiple sclerosis: A systematic scoping review. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes in patients with relapsing forms of MS switching to teriflunomide from other disease-modifying therapies: Results from the global Phase 4 Teri-PRO study in routine clinical practice. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Long-Term Improvement and Safety of Aripiprazole for Irritability and Adaptive Function in Asian Children and Adolescents with Autistic Disorder: A 52-Week, Multinational, Multicenter, Open-Label Study. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

CYP2D6 Genotype and Pharmacovigilance Impact on Autism Spectrum Disorder: A Naturalistic Study with Extreme Phenotype Analysis. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Novel and emerging treatments for autism spectrum disorders: a systematic review. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Prescription Drug Use and Polypharmacy Among Medicaid-Enrolled Adults with Autism: A Retrospective Cross-Sectional Analysis. [2020]

10. Australia pubmed.ncbi.nlm.nih.gov

An open-label extension long-term study of the safety and efficacy of aripiprazole for irritability in children and adolescents with autistic disorder in Japan. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Reduced epilepsy development in synapsin 2 knockout mice with autistic behavior following early systemic treatment with interleukin-6 receptor antibody. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Autism Spectrum Disorder: Classification, diagnosis and therapy. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Changes in prevalence of autism spectrum disorders in 2001-2011: findings from the Stockholm youth cohort. [2022]

14. United States pubmed.ncbi.nlm.nih.gov

Brain IL-6 and autism. [2013]

15. Netherlands pubmed.ncbi.nlm.nih.gov

Brain IL-6 elevation causes neuronal circuitry imbalances and mediates autism-like behaviors. [2016]