Evaluation of Arbaclofen for Biomarker-Based Treatment of Social Function in Pediatric Autism Spectrum Disorder: A Follow-Up Shiftability Study
- Trial ID
- 2023-508407-20-00
- Protocol
- AIMS-2-CT2
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to predict the long-term response to **arbaclofen** based on a single dose response during the placebo-controlled randomized single dose double-blind stage. This is clinically relevant as it aims to establish a predictive model for treatment efficacy in children and adolescents with autism spectrum disorder, potentially guiding personalized therapeutic strategies.
Secondary objectives include testing the effect of arbaclofen on an EEG biomarker for response to faces during the placebo-controlled randomized single dose double-blind stage. This could provide insights into the neurophysiological mechanisms underlying social function improvements in this population.
Participants
The clinical trial involves participants diagnosed with **autism spectrum disorder** according to DSM-5 criteria. The study population includes both male and female subjects aged between 7 to 23 years at the time of consent. Participants are required to have stable pharmacological and psychotherapeutic regimens affecting behavior prior to and during the study. The trial population is selected from individuals who have previously participated in the AIMS-2 CT1 study, with ages at recruitment ranging from 5 to 17 years, and are expected to be 2 to 5 years older at the start of this study in early 2024. Participants must reside with or have regular contact with a parent or caregiver who can provide reliable information about their condition. Females of childbearing potential must have a negative pregnancy test and agree to use effective contraception if sexually active. The trial includes a vulnerable population, and the sponsor has not provided the total number of participants involved in the study.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of **arbaclofen** in improving social function in children and adolescents diagnosed with **autism spectrum disorder**. This study is structured as a randomized, double-blind, placebo-controlled trial, followed by an open-label extension. The primary objective is to predict long-term response to arbaclofen based on a single-dose response during the initial placebo-controlled stage. The trial is expected to commence in August 2024 and conclude by July 2025, with a total duration of approximately 12 months.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, including age, diagnosis, and stability of current treatments. Following successful screening, participants will be randomized to receive either arbaclofen or placebo in the double-blind phase. The study will include regular follow-up visits to monitor safety, efficacy, and any adverse events. The primary endpoint is the latency of N170 change at week 14, with secondary endpoints assessing changes between treatment arms. The end-of-study visit will involve a comprehensive evaluation of the participant's response to treatment and overall health status.
Participant involvement is anticipated to last for the entire duration of the trial, approximately 12 months, unless early termination is warranted. Conditions that may lead to early withdrawal include significant adverse events, non-compliance with study procedures, or withdrawal of consent. The trial will adhere to rigorous ethical standards, ensuring informed consent is obtained from participants or their legal representatives before any study-related procedures are conducted. The study will utilize **arbaclofen** in oral solution form, with doses ranging from 5 mg to 20 mg, administered according to the trial protocol.
Treatment
The clinical trial involves the administration of **Arbaclofen**, a GABA-ergic agent, in various dosages as an **oral solution**. The experimental medication is provided in four different strengths: 5 mg, 10 mg, 15 mg, and 20 mg. Each formulation is designed for oral administration, with a maximum daily dose of 60 mg and a total maximum dose of 10,000 mg over a treatment period of up to 13 weeks. The active substance, **Arbaclofen**, also known as R-Baclofen or (3R)-4-amino-3-(4-chlorophenyl)butanoic acid, is of chemical origin. The pharmaceutical form is consistent across all dosages, ensuring uniformity in administration and absorption.
In addition to the experimental treatment, the study may include a placebo or comparator treatment as part of the trial design, although specific details on non-experimental treatments are not provided in the data. The trial aims to evaluate the long-term response to **Arbaclofen** based on a single-dose response during a placebo-controlled, randomized, single-dose, double-blind stage. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol and to accurately assess the efficacy and safety of the treatment.
Efficacy
The efficacy of the clinical trial will be assessed using specific endpoints to evaluate the response to **arbaclofen** in children and adolescents with Autism Spectrum Disorders. The primary endpoint is the change in latency of N170 at week 14. This parameter will be measured to determine the effect of the treatment over the specified period. Additionally, a secondary endpoint will assess the change in latency of N170 between different treatment arms, providing comparative data on the efficacy of the intervention.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed Written Informed Consent a. Participants or their legal representative must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care. Participants who do not have the capacity to consent will give developmentally appropriate assent. Participants who become adults (18 years of age) during the trial will sign a specific consent during the first visit when they are 18. b. Participants must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing. c. The participant’s parent/caregiver/LAR must be able to speak and understand the local language where the study is conducted sufficiently to understand the nature of the study and to allow for the completion of all study assessments. The same parent/caregiver/LAR must be capable of providing reliable information about the participant’s condition, agree to oversee the administration of study drug, and accompany the participant to all clinic visits. d. Patient must be able to speak and understand the local language where the study is conducted sufficiently to understand the nature of the study and to allow for the completion of all study assessments.
- Type of Participant and Target Disease Characteristics a. Diagnosis of an Autism Spectrum Disorder according to the DSM-5 criteria b. Participarts are within the age-range: 5 to 23yo. c. Current pharmacological treatment regimen affecting behaviour has been stable for at least 6 weeks prior to screening and is expected to be stable during the duration of the study. d. Current psychotherapeutic/psychosocial interventions affecting behaviour stable for 3 months prior to screening and expected to be stable during the duration of the study (standard regular school breaks and/or annual teacher/classroom change do not qualify for intervention change). e. Participants with a history of seizure disorder must currently be receiving stable treatment with anticonvulsant medication and must have been seizure free for 6 months prior to screening or must be seizure free for 3 years prior to screening if not currently on a stable (>3 months) dose of antiepileptics.
- Age, Residential and Reproductive Status a. Male or female participants 7 to 23 years of age at the time of providing consent, inclusive. b. Reside or regular contact (at least twice a week) with the parent/carer who is interviewed for the study. c. Negative pregnancy test for females of childbearing potential (participant has experienced onset of menses) d. Females of childbearing potential who are sexually active must agree to use a highly effective form of contraception (i.e., existing surgical sterilization, complete or abstinence or a combination of two affective forms of contraception, such as, for example, condoms plus hormonal treatment). Please, refer to Appendix 4 for a complete list of acceptable contraception methods. e. Male participants with female partners of childbearing potential are eligible to participate if they agree to the conditions stated in section 8.2.1.
Exclusion Criteria
- Medical Conditions a. Participants with any condition that might interfere with the conduct of the study, confound interpretation of the study results, or endanger their own well-being. This includes, but is not limited to impairment of renal function, evidence or history of malignancy or any significant haematological, endocrine, respiratory, hepatic, cardiovascular or gastrointestinal disease, including any clinically significant abnormalities on ECG. In general, any co-morbid conditions that may interact with study procedures. b. Participants previously excluded from AIMS-2 CT1 due to adverse events.
- Prior/Concomitant Therapy a. Participants who are currently receiving treatment with racemic baclofen, vigabatrin, tiagabine, or riluzole or other GABA-related medications (e.g. gabapentin or pregabalin) other than arbaclofen in the context of AIMS-2 CT1. Only occasional benzodiazepine (or derivative drugs) use (PM, i.e. at night) will be allowed. However, participants will be asked to abstain from it, if possible, the night before the recording of the EEG (i.e. visits 1, 2 and 7). b. Participants who are currently receiving pharmacologic treatment affecting behaviour (see concomitant medication section) need to have a stable dose during the 6 weeks prior to the screening visit and for the duration of the study. c. Participating in programs including non-pharmacologic educational, behavioural, and/or dietary interventions affecting behaviour, participation in these programs must have been continuous during the 3 months prior to screening and participants or their parent/caregiver/LAR may not electively initiate new or modify ongoing interventions for the duration of the study. Typical school vacations are not considered modifications of stable programming. d. Participants who have taken another investigational drug within the last 30 days.
- Physical and Laboratory Test Findings a. Participants with evidence of any significant haematological, endocrine, cardiovascular (including uncorrected symptomatic congenital heart disease), respiratory, renal, hepatic, or gastrointestinal disease, not including mild common paediatric diseases in these areas that are stable (e.g. mild asthma, constipation, etc.), as judged by the investigator.
- Study-medication related a. Participants who are not able to take oral medications. b. Participants who have a history of hypersensitivity to racemic baclofen. c. Participants with rare hereditary problems of galactose intolerance, the lactase deficiency or glucose-galactose malabsorption should not take this medicine. d. Active peptic ulceration as Baclofen stimulates gastric acid secretion. e. Porphyria.
- Other exclusion criteria a. Participants who are currently engaged in illicit drug use or alcohol abuse, according to DSM-5 criteria. b. Participants who have previously participated in a clinical trial with arbaclofen (other than our AIMS-2-CT1). c. Women who are breastfeeding.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 01 Aug 2024 | 20 |
 Spain | Recruiting | 01 Aug 2024 | 85 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
ARBACLOFEN 10mg | Test | ORAL SOLUTION | ORAL | 60 | 13 | PRD11301957 |
ARBACLOFEN 5mg | Test | ORAL SOLUTION | ORAL | 60 | 13 | PRD11301956 |
ARBACLOFEN 15mg | Test | ORAL SOLUTION | ORAL | 60 | 13 | PRD11301958 |
ARBACLOFEN 20mg | Test | ORAL SOLUTION | ORAL | 60 | 13 | PRD11301959 |