ARD-501 for Autism

Recruiting in Palo Alto (17 mi)

Overseen by Ann Childress, M.D.

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: Aardvark Therapeutics, Inc.

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests a new medication called ARD-501 for safety and effectiveness in people with Autism Spectrum Disorder (ASD). Participants will receive the medication in two different doses to compare results. The goal is to see if ARD-501 can help improve symptoms of ASD.

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

The trial requires that you stop taking certain medications. You cannot use scheduled benzodiazepines, baclofen, gabapentin, pregabalin, supplements affecting the GABA system, any cannabinoids, or opioids. Also, your mood, anxiety, or behavior medication doses must be stable for 4 weeks before the trial.

What data supports the idea that ARD-501 for Autism is an effective treatment?

The available research does not provide any data supporting the effectiveness of ARD-501 for Autism. The studies focus on the use of androgen deprivation therapy (ADT) in combination with radiotherapy for prostate cancer, not Autism. Therefore, there is no information to compare ARD-501 to other treatments for Autism or to demonstrate its effectiveness for this condition. ^{1 2 3 4 5}

What safety data exists for ARD-501 in treating autism?

The safety data for ARD-501, also known as aripiprazole, includes several studies. A randomized, double-blind, placebo-controlled study in Japan found aripiprazole to be generally safe and well-tolerated in children and adolescents with autism spectrum disorder, with no serious adverse events reported. An open-label extension study and a 52-week post-marketing surveillance study in Japan also supported its safety, with common treatment-emergent adverse events being nasopharyngitis and weight increase. A multinational, 52-week open-label study reported a 5.17% incidence of serious adverse events, including epiphysiolysis, seizure, and a suicide attempt, but these were not considered adverse drug reactions. Overall, aripiprazole was well-tolerated with improvements in behavioral problems and adaptive functioning. ^{6 7 8 9 10}

Is the drug ARD-501 a promising treatment for autism?

Yes, ARD-501, also known as aripiprazole, is a promising treatment for autism. It has shown effectiveness in improving sensory abnormalities, reducing irritability and aggression, and enhancing overall behavior in children and adolescents with autism spectrum disorder. ^{10 11 12 13 14}

Research Team

Ann Childress, M.D.

Principal Investigator

Center for Psychiatry and Behavioral Medicine

Eligibility Criteria

This trial is for males and females aged 17-25 with Autism Spectrum Disorder, confirmed by DSM-5 criteria and specific assessments. Participants must be in good health, understand the study, and agree to follow its rules. Sexually active participants must use effective birth control methods.

Inclusion Criteria

I am using a reliable birth control method that is not dependent on daily use.

You have a score of 76 or higher on the SRS™-2 test adjusted for your age group.

I have been diagnosed with ASD based on DSM-5 and ADOS-2.

Treatment Details

Interventions

• ARD-501 (Other)

Trial Overview The study tests two different doses of ARD-501 against a placebo in people with ASD. It's blinded, meaning participants don't know what they're getting, and it uses a cross-over design so everyone gets each treatment at some point.

Participant Groups

Group I: Phase 2: High Dose Experimental Treatment 1 Intervention

ARD-501 for 7 days at 0.5 mg/kg

Group II: Phase 2: Crossover Placebo to High Dose Experimental Treatment 1 Intervention

ARD-501 for 7 days at 0.5 mg/kg

Group III: Phase 1: Low Dose Experimental Treatment 1 Intervention

ARD-501 for 7 days at 0.2 mg/kg

Group IV: Phase 2: Crossover High Dose to Placebo Placebo Group 1 Intervention

Placebo for 7 days

Group V: Phase 2: Placebo Placebo Group 1 Intervention

Placebo for 7 days

Who Is Running the Clinical Trial?

Aardvark Therapeutics, Inc.

Lead Sponsor

Trials

5

Recruited

150+

Center for Psychiatry And Behavioral Medicine Inc.

Industry Sponsor

Trials

2

Recruited

100+

Findings from Research

The review of literature on androgen deprivation therapy (ADT) combined with dose-escalated radiation therapy (RT) shows mixed results, with some studies indicating potential benefits while others do not.

The overall effectiveness of adding ADT to dose-escalated RT remains uncertain, highlighting the need for ongoing prospective randomized trials to clarify its role in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current role of androgen deprivation in patients undergoing dose-escalated external beam radiation therapy for clinically localized prostate cancer. Smith, MJ., Akhtar, NH., Tagawa, ST.[2021]

In a study using R3327-G Dunning rat prostate tumor cells, the sequence of androgen deprivation (AD) followed by radiotherapy (RT) resulted in the longest tumor doubling time, indicating prolonged suppression of tumor growth, even after testosterone restoration.

The findings suggest that administering RT after a period of AD is more effective than other sequences, highlighting the importance of treatment timing in enhancing the efficacy of combined therapies for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of sequencing of androgen deprivation and radiotherapy on prostate cancer growth. Kaminski, JM., Hanlon, AL., Joon, DL., et al.[2019]

In a study of 373 intermediate-risk prostate cancer patients treated with radiotherapy over 14 years, those aged 70 or younger who received radiotherapy alone had a higher risk of biochemical failure compared to those who received combined radiotherapy and androgen deprivation therapy (ADT).

The results suggest that short-term ADT may be beneficial for younger patients with favorable intermediate-risk prostate cancer, as it improved biochemical relapse-free survival from 82.1% to 94.0% compared to radiotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy with or without androgen deprivation therapy in intermediate risk prostate cancer? Amit, U., Lawrence, YR., Weiss, I., et al.[2020]

In a study of 18,598 men with favorable intermediate-risk prostate cancer, adding androgen-deprivation therapy (ADT) to modern dose-escalated radiotherapy (RT) did not improve overall survival rates, with 8-year survival at 77.7% for ADT plus RT and 78.4% for RT alone.

The findings suggest that for patients with favorable intermediate-risk prostate cancer, using dose-escalated RT alone may be a reasonable treatment option, as ADT did not show survival benefits and carries potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the effectiveness of adding androgen deprivation to modern dose-escalated radiotherapy for men with favorable intermediate-risk prostate cancer. Falchook, AD., Basak, R., Mohiuddin, JJ., et al.[2018]

In a study of 14,126 patients with intermediate-risk prostate cancer, adding androgen-deprivation therapy (ADT) to high-dose radiation therapy (RT) did not show an overall survival benefit compared to RT alone, indicating that ADT may not be necessary for all patients in this group.

However, patients with all three intermediate-risk factors did experience a significant survival benefit from ADT, suggesting that this treatment may be beneficial for a specific subset of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival outcomes of radiotherapy with or without androgen-deprivation therapy for patients with intermediate-risk prostate cancer using the National Cancer Data Base. Amini, A., Rusthoven, CG., Jones, BL., et al.[2022]

In an 8-week study involving 92 children and adolescents with autism spectrum disorder, aripiprazole significantly reduced irritability compared to placebo, as measured by parent/caregiver and clinician ratings.

Aripiprazole was found to be effective and well-tolerated, with no serious adverse events reported, indicating a favorable safety profile for treating irritability in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole in the Treatment of Irritability in Children and Adolescents with Autism Spectrum Disorder in Japan: A Randomized, Double-blind, Placebo-controlled Study. Ichikawa, H., Mikami, K., Okada, T., et al.[2022]

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 study involving 510 pediatric patients with autism spectrum disorder, aripiprazole demonstrated a high continuation rate of treatment, with 84.6% of patients still on the medication after 24 weeks, indicating its effectiveness and tolerability in real-world settings.

The treatment led to a significant reduction in irritability symptoms, as measured by the Aberrant Behavior Checklist, with a mean score change of -5.7 after 4 weeks, showing that aripiprazole can effectively manage irritability in children and adolescents with ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole in the real-world treatment for irritability associated with autism spectrum disorder in children and adolescents in Japan: 52-week post-marketing surveillance. Sugimoto, Y., Yamamura, K., Takayama, T., 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]

In a study of 13 children and adolescents with autism, aripiprazole was found to improve sensory deficits and disruptive behaviors over an average treatment duration of 24.4 weeks.

The medication showed specific benefits in areas such as auditory processing and visual input modulation, indicating its potential effectiveness in addressing sensory abnormalities associated with autism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective review of the effectiveness of aripiprazole in the treatment of sensory abnormalities in autism. Fung, LK., Chahal, L., Libove, RA., et al.[2015]

Aripiprazole has been shown to be effective in reducing behavioral disturbances in children and adolescents with autism spectrum disorder (ASD), particularly in areas like irritability, hyperactivity, inappropriate speech, and stereotypic behavior, based on a meta-analysis of 408 randomized patients.

The treatment was found to be safe and well-tolerated, with a lower discontinuation rate due to adverse events compared to placebo, although it did not significantly improve lethargy or social withdrawal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole in acute treatment of children and adolescents with autism spectrum disorder: a systematic review and meta-analysis. Maneeton, N., Maneeton, B., Putthisri, S., et al.[2022]

In a preliminary study involving 5 children and adolescents with pervasive developmental disorders, aripiprazole was found to be effective, with all participants showing improvement according to the Clinical Global Impressions-Improvement scale.

The treatment was well tolerated, with no significant adverse effects reported, although mild somnolence was noted in two patients and some weight loss occurred, likely due to the discontinuation of other medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole for maladaptive behavior in pervasive developmental disorders. Stigler, KA., Posey, DJ., McDougle, CJ.[2015]

In a study of 82 children aged 2 to 13 with autism spectrum disorder (ASD), treatment with risperidone or aripiprazole led to significant improvements in challenging behaviors, with 96% of patients showing notable improvement according to the Clinical Global Impression scale.

While the medications were effective, some side effects were noted, including elevated prolactin levels in 12 patients and weight gain in 2 patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Core Signs and Symptoms in Children with Autism Spectrum Disorder Improved after Starting Risperidone and Aripiprazole in Combination with Standard Supportive Therapies: A Large, Single-Center, Retrospective Case Series. Alsayouf, HA., Talo, H., Biddappa, ML.[2023]

Aripiprazole is an atypical antipsychotic that has been approved for treating irritability and aggression in children and adolescents aged 6-17 with autism spectrum disorder, based on evidence from randomized controlled trials.

The effectiveness and safety of aripiprazole can vary significantly among individuals with autism due to the disorder's heterogeneity, suggesting that patient subgrouping and consideration of underlying causes of symptoms are important for optimal treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole for the treatment of irritability and aggression in children and adolescents affected by autism spectrum disorders. Rizzo, R., Pavone, P.[2018]

References

1. Egypt pubmed.ncbi.nlm.nih.gov

The current role of androgen deprivation in patients undergoing dose-escalated external beam radiation therapy for clinically localized prostate cancer. [2021]

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

Effect of sequencing of androgen deprivation and radiotherapy on prostate cancer growth. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Radiotherapy with or without androgen deprivation therapy in intermediate risk prostate cancer? [2020]

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

Evaluation of the effectiveness of adding androgen deprivation to modern dose-escalated radiotherapy for men with favorable intermediate-risk prostate cancer. [2018]

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

Survival outcomes of radiotherapy with or without androgen-deprivation therapy for patients with intermediate-risk prostate cancer using the National Cancer Data Base. [2022]

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

Aripiprazole in the Treatment of Irritability in Children and Adolescents with Autism Spectrum Disorder in Japan: A Randomized, Double-blind, Placebo-controlled Study. [2022]

7. 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]

8. England pubmed.ncbi.nlm.nih.gov

Aripiprazole in the real-world treatment for irritability associated with autism spectrum disorder in children and adolescents in Japan: 52-week post-marketing surveillance. [2021]

9. 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]

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

A retrospective review of the effectiveness of aripiprazole in the treatment of sensory abnormalities in autism. [2015]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Aripiprazole in acute treatment of children and adolescents with autism spectrum disorder: a systematic review and meta-analysis. [2022]

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

Aripiprazole for maladaptive behavior in pervasive developmental disorders. [2015]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Core Signs and Symptoms in Children with Autism Spectrum Disorder Improved after Starting Risperidone and Aripiprazole in Combination with Standard Supportive Therapies: A Large, Single-Center, Retrospective Case Series. [2023]

14. England pubmed.ncbi.nlm.nih.gov

Aripiprazole for the treatment of irritability and aggression in children and adolescents affected by autism spectrum disorders. [2018]