Arbaclofen for Autism

(ARBA Trial)

No longer recruiting at 3 trial locations

Overseen By Lisa Genore

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Evdokia Anagnostou

Must not be taking: Baclofen, Vigabatrin, Tiagapine, others

Disqualifiers: Pregnancy, Serious medical conditions, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness and safety of arbaclofen in improving social skills for children and adolescents with Autism Spectrum Disorder (ASD). Participants will receive either arbaclofen or a placebo (a pill with no active medication) to compare outcomes. It suits those aged 5 to 17 with an ASD diagnosis who have been stable in their current treatments or therapies for some time. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important early-stage findings.

Will I have to stop taking my current medications?

If you are already on stable medications affecting behavior, you can continue them as long as they haven't changed in the last 6 weeks and won't change during the study. However, you cannot take certain medications like racemic baclofen, vigabatrin, tiagapine, riluzole, clobazam, or regular benzodiazepines.

Is there any evidence suggesting that arbaclofen is likely to be safe for humans?

Research has shown that arbaclofen has been tested for safety and effectiveness in various conditions. Studies have found that people generally tolerate arbaclofen well. For example, in a study involving individuals with multiple sclerosis, arbaclofen significantly reduced muscle stiffness and was considered safe. Another study demonstrated that arbaclofen was well-tolerated by individuals with spinal cord injuries at certain doses.

In children with Fragile X Syndrome, which shares some similarities with autism, arbaclofen has been studied for its effects on social withdrawal. The results suggest it was safe to use. Together, these studies indicate that arbaclofen is considered safe for humans in the situations tested. However, individual experiences can differ, and joining a clinical trial helps researchers learn more about the treatment's effectiveness and safety for everyone. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ASD?

Unlike the standard treatments for autism spectrum disorder (ASD), which often focus on behavioral interventions and medications like antipsychotics to manage symptoms, Arbaclofen offers a novel approach by targeting the GABA-B receptor in the brain. This mechanism aims to improve social functioning and reduce irritability by enhancing inhibitory neurotransmission, which is not the primary focus of existing medications. Researchers are excited about Arbaclofen because it has the potential to address core symptoms of ASD more directly, offering families a new hope for more effective management of the condition.

What evidence suggests that arbaclofen might be an effective treatment for Autism Spectrum Disorder?

Research shows that arbaclofen, which participants in this trial may receive, might help with symptoms of Autism Spectrum Disorder (ASD). Earlier studies found that it can significantly improve key areas of ASD, such as communication and repetitive behaviors. In children and teens with ASD, researchers tested arbaclofen for safety and effectiveness, yielding promising results. It also improved social skills in other related conditions, suggesting potential usefulness for ASD. Overall, these findings suggest that arbaclofen might enhance social interaction in people with ASD. ^{6 7 8 9 10}

Who Is on the Research Team?

Evdokia Anagnostou, M.D

Principal Investigator

Holland Bloorview Kids Rehabilitation Hospital

Robert Nicolson, M.D

Principal Investigator

University of Western Ontario, Lawson Health Research Institute

Julia Frei, M.D

Principal Investigator

McMaster University, Offord Centre for Child Studies

Muhammad Ayub, M.D

Principal Investigator

Queen's University

Are You a Good Fit for This Trial?

Inclusion Criteria

Outpatients 5-17 years of age inclusive.

Meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). DSM-5 criteria will be established by a clinician with expertise with individuals with ASD. Diagnosis will be supported by the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2).

Complex language to qualify for ADOS-2 modules 3 or 4.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive arbaclofen or placebo to assess its effect on social function in children and adolescents with ASD

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Arbaclofen
• Placebo

How Is the Trial Designed?

Group I: Arbaclofen Active Control 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Evdokia Anagnostou

Lead Sponsor

Trials

12

Recruited

640+

Holland Bloorview Kids Rehabilitation Hospital

Lead Sponsor

Trials

69

Recruited

14,100+

Kingston Health Sciences Centre

Collaborator

Trials

312

Recruited

112,000+

Western University, Canada

Collaborator

Trials

270

Recruited

62,500+

Queen's University

Collaborator

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

University of Western Ontario, Canada

Collaborator

Trials

168

Recruited

320,000+

Queen's University

Collaborator

Trials

382

Recruited

122,000+

Unity Health Toronto

Collaborator

Trials

572

Recruited

470,000+

Published Research Related to This Trial

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

In a review of 109 clinical studies with 1228 healthy volunteers, 19% reported adverse events during placebo administration, highlighting that even without active treatment, participants can experience side effects.

Adverse events were more common with repeated dosing (28%) and among elderly participants (26%), with headaches, drowsiness, and asthenia being the most frequently reported issues, indicating that placebo effects can significantly influence safety evaluations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The placebo effect in healthy volunteers: influence of experimental conditions on the adverse events profile during phase I studies. Rosenzweig, P., Brohier, S., Zipfel, A.[2023]

The study analyzed adverse event (AE) data from six randomized controlled trials involving schizophrenia treatments, highlighting that the absolute prevalence and expected duration of AEs provide a more comprehensive understanding of a drug's safety compared to just incidence rates.

Using a new metric to assess the drug-placebo difference in AE prevalence, the research found that some AEs not listed in the standard drug label significantly impacted drug tolerability, suggesting that including these metrics in drug labels could enhance safety signal detection and inform better treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Method for Deriving Adverse Event Prevalence in Randomized Controlled Trials: Potential for Improved Understanding of Benefit-Risk Ratio and Application to Drug Labels. Piacentino, D., Ogirala, A., Lew, R., et al.[2023]

The study systematically analyzed placebo effects from randomized, placebo-controlled trials, revealing that while placebos can influence clinical symptoms, they do not affect laboratory values like blood glucose in diabetics.

Placebo side effects were found to be similar to those of active treatments, highlighting the importance of careful placebo use in clinical research to ensure patient safety and informed consent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo treatment is effective differently in different diseases--but is it also harmless? A brief synopsis. Weihrauch, TR.[2019]

Citations

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Arbaclofen extended-release tablets for spasticity in ... Arbaclofen extended-release treatment (up to 80 mg/day) was well tolerated and reduced symptoms of spasticity in adult patients with multiple sclerosis for 1 ...

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Arbaclofen in Children and Adolescents With ASD AIMS-2-CT-01 is a randomized, double-blind, placebo controlled, study to explore the efficacy, safety and tolerability of Arbaclofen administered to ...

3. allospharma.com allospharma.com/allos-pharma-acquires-global-rights-to-arbaclofen-reports-positive-asd-trial-results-and-grant-award/

Allos Pharma Acquires Global Rights to Arbaclofen ... Significant improvements were also observed in the core ASD domains of communication and restricted/repetitive behaviors. These results provide ...

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Arbaclofen in fragile X syndrome: results of phase 3 trials - PMC Arbaclofen improved multiple abnormal phenotypes in animal models of fragile X syndrome (FXS) and showed promising results in a phase 2 clinical study.

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Study Protocol for AIMS-2-TRIALS-CT1 The AIMS2TRIALS-Clinical Trial 1 (AIMS-CT1) will examine whether arbaclofen is superior to placebo in improving social function and other ...

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Clinical potential, safety, and tolerability of arbaclofen in the ... Preliminary clinical studies support the notion that arbaclofen in the form of STX209 has promise for improving social function in the ASD population.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03290131

NCT03290131 | A Study to Investigate the Safety and ... A Study to Investigate the Safety and Effectiveness of Arbaclofen Extended-Release Tablets for Patients With MS (OS440-3004). ClinicalTrials.gov ID NCT03290131.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT01325220

NCT01325220 | Efficacy and Safety Study of STX209 ... Efficacy and Safety Study of STX209 (Arbaclofen) for the Treatment of Social Withdrawal in Children With Fragile X Syndrome (Harbor-C). ClinicalTrials.gov ID ...

9. nature.com nature.com/articles/sc201143

Efficacy and safety study of arbaclofen placarbil in patients ... AP was well tolerated at all investigated dosages and, when administered at doses of 20 or 30 mg twice daily, was efficacious in reducing spasticity due to SCI.

10. academic.oup.com academic.oup.com/braincomms/article/4/6/fcac300/6841350

Arbaclofen extended-release tablets for spasticity in multiple ... Arbaclofen extended-release 40 mg/day for 12 weeks significantly reduced multiple sclerosis-related spasticity compared with placebo and was safe and well ...