ARD-501 for Autism

Overseen By Alexa M Warner, BSc

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Aardvark Therapeutics, Inc.

Must not be taking: Benzodiazepines, Cannabinoids, Opioids, others

Disqualifiers: Seizure disorder, Major depressive disorder, others

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

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, ARD-501, for people with Autism Spectrum Disorder (ASD). Researchers aim to determine the safety of this medication at different doses. Participants will receive either a low or high dose of ARD-501 or a placebo (a harmless pill with no effect). The trial seeks individuals diagnosed with ASD who are in generally good health. 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 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.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as benzodiazepines, baclofen, gabapentin, pregabalin, and any cannabinoids. If you're on mood, anxiety, or behavior medications, your dosage must be stable for at least 4 weeks before starting the trial.

Is there any evidence suggesting that ARD-501 is likely to be safe for humans?

Research has shown that ARD-501, also known as aripiprazole, has undergone safety testing in earlier studies. In Japan, a study was conducted where neither participants nor researchers knew who received the actual treatment or a placebo (a harmless pill with no effect). This study gathered safety information about ARD-501.

The research tested two different doses of ARD-501 and found that most people did not experience serious side effects, indicating the treatment was generally well-tolerated. These safety findings apply to both the lower and higher doses tested.

Overall, while ARD-501 appears promising and has been studied before, the current trial will provide more information about its safety specifically for people with autism. ^{1 2 3 4 5}

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

ARD-501 is unique because it offers a potentially faster-acting treatment option for autism compared to current therapies like behavioral interventions and medications such as antipsychotics and antidepressants, which can take weeks to show effects. Researchers are excited about ARD-501 because it targets autism symptoms directly and may demonstrate results in just seven days, which is much quicker than existing treatments. Additionally, the trial explores both low and high doses of ARD-501, providing insight into its efficacy and safety at different levels, which could lead to more tailored treatment options.

What evidence suggests that ARD-501 might be an effective treatment for autism?

Research has shown that ARD-501, also known as aripiprazole, may help treat autism. It has effectively improved sensory issues, common challenges for people with autism. Some studies suggest it can reduce these sensory problems and might also help with other symptoms. In this trial, researchers are studying both low and high doses of ARD-501 to evaluate their effectiveness. While not yet fully proven, ARD-501's potential benefits make it a hopeful option for those with Autism Spectrum Disorder. ^{1 3 5 6 7}

Who Is on the Research Team?

Ann Childress, M.D.

Principal Investigator

Center for Psychiatry and Behavioral Medicine

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Phase 1 Treatment

Participants receive ARD-501 at 0.2 mg/kg for 7 days followed by a 7-day washout period

2 weeks

2 visits (in-person)

Phase 2 Treatment

Participants are randomized to receive ARD-501 at 0.5 mg/kg and placebo in a cross-over design, each for 7 days with a 7-day washout period

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ARD-501

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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 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 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]

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 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 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]

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 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]

Citations

1. withpower.com withpower.com/trial/phase-2-autistic-disorder-10-2023-badb0

ARD-501 for Autism · Info for Participants Yes, ARD-501, also known as aripiprazole, is a promising treatment for autism. It has shown effectiveness in improving sensory abnormalities, reducing ...

2. trialx.com trialx.com/clinical-trials/listings/254386/a-study-to-evaluate-ard-501-in-patients-with-autism-spectrum-disorder/

A Study to Evaluate ARD-501 in Patients With Autism ... Overview. This is a blinded, placebo controlled, cross-over trial evaluating the safety of two dose-levels of ARD-501 in subjects with ASD.

3. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/ard-501-aardvark-therapeutics-autism-spectrum-disorder-asd-likelihood-of-approval/

ARD-501 by Aardvark Therapeutics for Autism Spectrum ... According to GlobalData, Phase II drugs for Autism Spectrum Disorder (ASD) have a 49% phase transition success rate (PTSR) indication benchmark ...

4. clinconnect.io clinconnect.io/trials/NCT06126653

A Study to Evaluate ARD-501 in Patients With Autism This is a blinded, placebo controlled, cross-over trial evaluating the safety of two dose-levels of ARD-501 in subjects with ASD.

5. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06126653/

Trial | NCT06126653 This study is a blinded, placebo controlled, cross-over trial evaluating the safety and efficacy of two dose levels in subjects with Autism Spectrum Disorder.

6. ctv.veeva.com ctv.veeva.com/study/a-study-to-evaluate-ard-501-in-patients-with-autism-spectrum-disorder

A Study to Evaluate ARD-501 in Patients With Autism ... This is a blinded, placebo controlled, cross-over trial evaluating the safety of two dose-levels of ARD-501 in subjects with ASD.

7. go.drugbank.com go.drugbank.com/conditions/DBCOND0006160

Autism Spectrum Disorder (DBCOND0006160) An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum ... A Study to Evaluate ARD-501 in Patients With Autism ...