ML-004 for Autism Spectrum Disorder

Recruiting at 30 trial locations

Overseen By Mark DiBuono, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: MapLight Therapeutics

Disqualifiers: Rett syndrome, Epilepsy, Hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to test whether a new medication, ML-004, can improve social communication skills in individuals with Autism Spectrum Disorder (ASD). Participants will take either ML-004 or a placebo (a pill with no active medication) once daily. The trial seeks individuals aged 12 to 45 who have been diagnosed with ASD and have stable treatment plans for any other psychoactive medications. 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 advancements in ASD treatment.

Do I need to stop my current medications to join the trial?

The trial requires that any psychoactive medications and therapies you are taking must be stable for at least 4 weeks before you start the trial. This means you should not change your current medications during that time.

Is there any evidence suggesting that ML-004 is likely to be safe for humans?

Research shows that specific safety information for ML-004 in humans is not yet available. However, a similar treatment, aripiprazole, has been studied and is generally well-tolerated. The FDA has approved aripiprazole for other uses, suggesting its safety. This might indicate that ML-004 could also be safe, but ML-004 is still under investigation. As this study is in Phase 2, early safety tests have been completed, but more data is needed to fully understand its safety in humans. Researchers will closely monitor participants for any side effects. ^{1 2 3 4 5}

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

ML-004 is unique because it combines both immediate-release and extended-release mechanisms in a single oral tablet, which is not typical in current autism treatments. Unlike many traditional medications that may require multiple doses throughout the day, ML-004 simplifies treatment by being taken just once daily. This could improve adherence and maintain more consistent therapeutic levels in the body. Researchers are excited about this treatment as it potentially offers a more convenient and effective option for managing symptoms of Autism Spectrum Disorder.

What evidence suggests that ML-004 might be an effective treatment for ASD?

Research has shown that ML-004, which participants in this trial may receive, might improve social communication in people with Autism Spectrum Disorder (ASD). Previous participants demonstrated promising improvements in sociability, such as better eye contact and social interactions. Early studies used eye tracking to measure these improvements, suggesting that ML-004 may enhance social engagement. In this trial, the treatment is provided as a once-daily tablet with varying doses, combining both immediate and extended release for effectiveness. While more data is needed, these initial findings offer hope for those considering ML-004 as a treatment option. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adolescents and adults aged 12 to 45 with Autism Spectrum Disorder (ASD) who can swallow pills. Participants need a care partner to report on symptoms, an IQ score of at least 70, and stable use of psychoactive meds for the past month. Excluded are those with certain other disorders, recent seizures or study participation, history of severe suicidal thoughts or actions, uncontrolled high blood pressure, or if pregnant/lactating.

Inclusion Criteria

Has a body mass index (BMI) 18 through 34 kg/m², inclusive

Full scale IQ (or equivalent) ≥55 score, with adequate verbal fluency, as determined by the Principal Investigator

Has a designated care/study partner who can reliably report on symptoms

Exclusion Criteria

Systolic blood pressure ≥140 mmHg (if adult) or >135 mmHg (if adolescent), or diastolic blood pressure ≥90 (if adult) or >85 mmHg (if adolescent), or a clinical history of uncontrolled or severe hypertension

Has Rett syndrome or Child Disintegrative Disorder

I have had seizures or uncontrolled epilepsy in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ML-004 or placebo once daily to evaluate efficacy in improving social communication deficits in ASD

16 weeks

Regular visits for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ML-004

Trial Overview The study tests ML-004 in tablet form against a placebo to see its effects on ASD. It's randomized meaning participants are put into the ML-004 or placebo group by chance and double-blind so neither researchers nor participants know who gets what treatment until after the results are collected.

How Is the Trial Designed?

Group I: ML-004 (IR)/(ER) tablet Experimental Treatment 1 Intervention

ML-004 is a bilayer immediate-release (IR)/extended-release (ER, gastroretentive) oral tablet formulation. ML-004 is taken orally once daily and provided as a tablet in two dose strengths of 12 mg (3 mg IR/9 mg ER) and 24 mg tablet (6 mg IR/18 mg ER). Dose levels for this study are 12 mg (provided as one 12 mg tablet), 24 mg (one 24 mg tablet), 48 mg (two 24 mg tablets), and 72 mg (three 24 mg tablets).

Group II: ML-004 Placebo Placebo Group 1 Intervention

Matched placebo oral tablets will consist of same excipients as the investigational drug but without any ML-004. Placebo taken orally once daily to match tablet number of ML-004 dose levels for 12 mg (1 tablet), 24 mg (1 tablet), 48 mg (2 tablets), and 72 mg (3 tablets).

Who Is Running the Clinical Trial?

MapLight Therapeutics

Lead Sponsor

Trials

3

Recruited

570+

Published Research Related to This Trial

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 study of 35 children with autism, aripiprazole treatment for 8 weeks significantly reduced illness severity and improved various behavioral symptoms, as measured by the Clinical Global Impression and Autism Treatment Evaluation Checklist.

The treatment was found to be safe, with no severe adverse effects reported, indicating that aripiprazole can be a viable option for managing autism-related behavioral disorders in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical observation of aripiprazole in the treatment of autism]. Xie, Q., Tang, J., Xu, Y., et al.[2015]

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]

In a pilot study involving 10 children aged 4-7 with autism spectrum disorder (ASD), 8 out of 9 participants who completed the study showed about a 33% improvement in autism symptoms after taking 1 gram of omega-3 fatty acids daily for 12 weeks.

The study found omega-3 fatty acids to be safe, with no reported side effects, suggesting they may be a beneficial intervention for children with ASD, although further research with larger groups is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega 3 fatty acid treatment in autism. Meiri, G., Bichovsky, Y., Belmaker, RH.[2009]

In a 6-week internet-based clinical trial involving 57 children with autism spectrum disorder, those receiving omega-3 fatty acids showed a greater reduction in hyperactivity compared to a placebo, although the difference was not statistically significant.

The study demonstrated that internet-based trials are feasible for evaluating treatments in children with ASD, with positive participant feedback and rare adverse events associated with omega-3 fatty acids, suggesting a safe profile for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Internet-based, randomized, controlled trial of omega-3 fatty acids for hyperactivity in autism. Bent, S., Hendren, RL., Zandi, T., et al.[2021]

Standard clinical outcome measures for multiple sclerosis (MS) include relapse rate and the Expanded Disability Status Scale, but the MS Functional Composite is gaining validation as a meaningful measure.

New imaging techniques, such as optical coherence tomography and advanced MRI methods, are being developed to improve the sensitivity of outcome measures in MS trials, particularly for relapsing-remitting MS and primary progressive MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges to clinical trials in multiple sclerosis: outcome measures in the era of disease-modifying drugs. Hyland, M., Rudick, RA.[2013]

In a study of 281 patients with neuromyelitis optica spectrum disorder (NMOSD), long-term treatment with mycophenolate mofetil (MMF) and azathioprine (AZA) significantly reduced the risk of relapse and motor disability compared to no immunotherapy, while corticosteroids showed no significant benefit.

The study identified key prognostic predictors for disability in NMOSD, including the onset of optic neuritis and older age at onset, highlighting the importance of early immunosuppressive treatment to delay disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of immunotherapies and prognostic predictors in neuromyelitis optica spectrum disorder: a prospective cohort study. Shi, Z., Du, Q., Chen, H., et al.[2021]

There is a critical need for a standardized and structured monitoring system for multiple sclerosis (MS) to effectively manage the disease, given its complex and varied progression.

The proposed MS monitoring matrix aims to integrate various measurement tools and utilize artificial intelligence to enhance treatment outcomes, patient safety, and personalized care for individuals with MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building a monitoring matrix for the management of multiple sclerosis. Voigt, I., Inojosa, H., Wenk, J., et al.[2023]

Natalizumab and anti-CD20 therapies (like rituximab and ocrelizumab) have shown superior efficacy in treating multiple sclerosis compared to older therapies, based on both randomized trials and observational studies involving various patient populations.

There is a shift towards early aggressive treatment strategies for multiple sclerosis, where patients are started on high-efficacy disease-modifying therapies (DMTs) right away, as opposed to the traditional escalation approach, with ongoing trials like TREAT-MS and DELIVER-MS evaluating the effectiveness of these strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Aggressive Treatment Approaches for Multiple Sclerosis. Simpson, A., Mowry, EM., Newsome, SD.[2022]

The 30-day readmission rate for patients with neuromyelitis optica spectrum disorder (NMOSD) was found to be 11.9%, indicating a significant risk of returning to the hospital shortly after discharge.

Older patients (aged 65 to 74) were at higher risk for readmission, while those with private insurance had lower odds; comorbidities like respiratory failure and neurocognitive disorders were also linked to increased readmission rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hospital Readmission Rates in Patients With Neuromyelitis Optica Spectrum Disorder. Padarti, A., Amritphale, A., Kilgo, W.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05081245

ML-004 in Adolescents and Adults With Autism Spectrum ... The primary objective is to evaluate the efficacy of ML-004 compared with placebo in the improvement of social communication deficits in subjects with ASD.

2. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/540235

ML-004 in Adolescents and Adults With Autism Spectrum ... The primary objective is to evaluate the efficacy of ML-004 compared with placebo in the improvement of social communication deficits in ...

3. maplightrx.com maplightrx.com/clinical-trials/

Clinical Trials The randomized, double blind, placebo-controlled study will evaluate the efficacy and safety profile of ML-004 in up to 150 adults and adolescents with ASD. The ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05889273

ML-004 Open-Label Extension Study in Adults and ... An Open-label Extension Study to Investigate Safety and Tolerability of ML-004 in Adolescents and Adults With Autism Spectrum Disorders (ASD). Conditions.

5. isctm.org isctm.org/public_access/21st_Annual/Poster/Abbs-Poster.pdf

The IRIS Trial for Investigational ML-004 in Autism ... Given these results, MapLight designed a Phase 2 trial to test whether ML-004 could increase sociability in individuals with ASD, including eye tracking as an ...

6. withpower.com withpower.com/trial/phase-3-autism-spectrum-disorder-10-2021-e6f27

ML-004 for Autism Spectrum Disorder What safety data exists for ML-004 in humans? There is no specific safety data available for ML-004, but aripiprazole, a similar treatment, has been studied ...