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Autism Spectrum DisorderPhase 2AIMS2-CT1NCT03682978

Arbaclofen in Children and Adolescents With ASD

A Phase 2 study testing Arbaclofen in people with Autism Spectrum Disorder, run by Celso Arango, MD, PhD at 7 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

AIMS-2-CT-01 is a randomized, double-blind, placebo controlled, study to explore the efficacy, safety and tolerability of Arbaclofen administered to children and adolescents (ages 5-17) for the treatment of social adaptive function in participants with ASD. Read more about this study

Who is it for?
Ages 5 to 17 years
Conditions the study is for
Autism Spectrum Disorder
What is being tested?
Arbaclofen
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
124 participants
Where
7 sitesin 3 countries
Study dates
19 Sep 2019to 27 Jan 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 5 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Signed Written Informed Consent
  • 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 must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
  • The subject'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 subject's condition, agree to oversee the administration of study drug, and accompany the subject to all clinic visits.
  • 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
Show all 22Show fewer
  • Diagnosis of an Autism Spectrum Disorder according to the DSM-5 criteria
  • Complex language as defined in ADOS-2 to qualify for a Module 3 or 4.
  • 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
  • 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).
  • Subjects 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
  • Male or female participants 5 to 17 years of age at the time of providing consent, inclusive.
  • Reside with the parent/carer who is interviewed for the Vineland.
  • Negative pregnancy test for females of childbearing potential (subject has experienced onset of menses) within 24h prior to study treatment starts.
  • Females of childbearing potential who are sexually active must agree to use a highly effective form of contraception (i.e., existing surgical sterilization, complete abstinence, or a combination of two effective forms of contraception, such as, for example, condoms plus hormonal treatment).
  • Male participants with female partners of childbearing potential are eligible to participate if they agree to the following conditions:
  • Inform any and all partner(s) of their participation in a clinical drug study and the need to comply with contraception instructions as directed by the investigator.
  • Male participants are required to use a condom for study duration and until end of relevant systemic exposure defined as 7 months after the end of study treatment.
  • Female partners of males participating in the study to consider use of effective methods of contraception until the end of relevant systemic exposure, defined as 7 months after the end of treatment in the male participant.
  • Male participants with a pregnant or breastfeeding partner must agree to remain abstinent from penile vaginal intercourse or use a male condom during each episode of penile penetration during the treatment and until 7 months after the end of study treatment.
  • Refrain from donating sperm for the duration of the study treatment and until 7 months after the end of study treatment.

Who cannot join

  • Medical Conditions
  • Subjects 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.
  • Prior/Concomitant Therapy
  • Subjects who are currently receiving treatment with racemic baclofen, vigabatrin, tiagabine, or riluzole or other GABA-related medications (e.g. gabapentin or pregabalin). Only occasional benzodiazepine (or derivative drugs) use (PM, i.e. at night) will be allowed.
  • Subjects 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.
  • 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.
Show all 19Show fewer
  • Subjects who have taken another investigational drug within the last 30 days.
  • Physical and Laboratory Test Findings
  • Patients with evidence of any significant hematological, endocrine, cardiovascular (including uncorrected symptomatic congenital heart disease), respiratory, renal, hepatic, or gastrointestinal disease, not including mild common pediatric diseases in these areas that are stable (e.g. mild asthma, constipation, etc.), as judged by the investigator.
  • Study Medication Related
  • Subjects who are not able to take oral medications.
  • Subjects who have a history of hypersensitivity to racemic baclofen.
  • Subjects with rare hereditary problems of galactose intolerance, the lactase deficiency or glucose-galactose malabsorption should not take this medicine.
  • Active peptic ulceration as Baclofen stimulates gastric acid secretion.
  • Porphyria.
  • Other Exclusion Criteria
  • Subjects who are currently engaged in illicit drug use or alcohol abuse, according to DSM-5 criteria.
  • Subjects who have previously participated in a clinical trial of Arbaclofen.
  • Women who are breastfeeding.

Trial locations and contacts

7 sites in 3 countries.

7 sites in 3 countries

Spain3 sites

  • Hospital Clínic de Barcelona

    Barcelona, 08036

  • Servicio de Psiquiatría del Niño y del Adolescente, Hospital General Universitario Gregorio Marañón, SERMAS

    Madrid, 28009

  • University of Salamanca & Complejo asistencial de Zamora

    Salamanca

Other trials in Spain

United Kingdom3 sites

  • University of Glasgow

    Glasgow, G78 1SL

  • King's College London

    London, SE5 8AF

  • University of Newcastle upon Tyne

    Newcastle, NE1 7RU

Other trials in United Kingdom

France1 site

  • Robert Debré Hospital

    Paris, 75019

Other trials in France

About this study

Official title: A Phase II Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety, and Tolerability of Arbaclofen Administered for the Treatment of Social Function in Children and Adolescents With Autism Spectrum Disorders

AIMS-2-CT-01 is a randomized, double-blind, placebo controlled, study to explore the efficacy, safety and tolerability of Arbaclofen administered to children and adolescents (ages 5-17) for the treatment of social adaptive function in participants with ASD. The effects of Arbaclofen on social function in children and adolescents with ASD will be evaluated in a randomized, placebo controlled, parallel-group study of 16 weeks duration. Subjects who meet protocol criteria will be randomly allocated to receive either Arbaclofen or placebo in a 1:1 ratio in the Treatment Period. There will be 7 recruiting sites and randomization will be stratified by site. A sample of 130 patients will be recruited. Blinding will be maintained by utilizing identical tablets containing either Arbaclofen or placebo.

Read the detailed description

Autism Spectrum Disorder (ASD) is a clinically and etiologically heterogeneous neurodevelopmental condition affecting approximately 1% of the population. The core symptoms of ASD are deficits in social communication and the presence of repetitive and restricted behaviours and interests, including sensory anomalies. Currently, there are no effective medical treatments for the core symptoms of ASD, and families frequently use costly non evidence based interventions. Developing drugs for ASD has been challenging because of a limited understanding of its underlying pathophysiology(ies), and difficulties modelling it in vitro and in vivo.

A recent study from EU-AIMS reported, for the first time in ASD, that differences in E-I balance can be 'shifted' using a GABA acting drug (riluzole), and that abnormalities in functional connectivity can be 'normalised' by targeting E-I, even in adults. This offers promise that drugs targeting specific parts of the GABA pathway may improve symptoms.

The aim of the investigator's project is to conduct a double-blind Randomized Control Trial (RCT) focused on GABA/glutamate equilibrium, to assess the efficacy of a drug that targets core and/or comorbid symptoms in ASD. Arbaclofen is a selective GABA-B receptor agonist and augments GABA-ergic activity, inhibits presynaptic release of glutamate, inhibits postsynaptic transmission, and modulates intracellular signalling. Through elevation of GABA-ergic inhibitory activity, Arbaclofen may act to alleviate ASD symptoms with social anxiety and emotional hyperarousal.

Hypothesis: Arbaclofen will be superior to placebo in improving social function as measured by the Vineland-3 social domain.

Being tested
Arbaclofen, Placebo
Keywords
Arbaclofen, Placebo-Controlled, Randomized, Double-Blind, Social Function, Efficacy, Safety, Tolerability, Children, Adolescents, ASD
Medical subject headings
Autism Spectrum Disorder, Social Adjustment

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ArbaclofenDrug

    Also called R-4-amino-3-(4-chlorophenyl) butanoic acid (R-baclofen), STX209, C10H12ClNO2

    Arbaclofen tablet.

  • PlaceboDrug

    Also called Placebo (for Arbaclofen)

    Placebo tablet.

Study groups in NCT03682978
Study groupRoleWhat they receive
ArbaclofenExperimentalArbaclofen is provided as orally disintegrating tabs, round, white and beveled edges, at the following strengths: 5mg, 10mg, 15mg and 20mg. A flexible dose titration schedule will be utilized during the first 5 weeks of the Treatment Period. Dosing regimens will be stratified by age. The total up-titration to 15 mg TID or 20 mg TID, and dose adjustment period to the optimal dose will be 35 days. If a participant does not tolerate a dose increase, he or she should return to the previous dose level and must remain at the dose level for the remainder of the Treatment Period. No changes should be made to dosing after 5 weeks, unless for safety. 5-11 years: Week 0 (BID) 5mg; Week 1 (BID) 5mg; Week 2 (TID) 10mg; Week 3 (TID) 10mg; Week 4-16 (TID) 15mg. 12-17 years: Week 0 (QD) 5mg; Week 1 (BID) 10mg; Week 2 (BID) 10mg; Week 3 (TID) 15mg; Week 4-16 (TID) 20mg.
Receives: Drug: Arbaclofen
PlaceboPlacebo comparatorPlacebo tablets will have similar form, colour, smell and taste compared to the Arbaclofen tablets, and will be provided in non-distinguishable packaging. Dosage level is n/a.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Effect of Arbaclofen vs. placebo on social function

    Vineland-3 (socialization domain): The Vineland Adaptive Behavior Scales, Third Edition is designed to assess the personal and social functioning of handicapped and non-handicapped persons. It is a gold standard for the assessment of adaptive functioning. The Socialization domain is one of the 4 adaptive domains assessed by the comprehensive interview form. The other 3 adaptive domains are communication, daily living skills and motor skills. The Socialization domain has 3 subdomains: interpersonal relations, play and leisure and coping skills.

    Measured: Week 0 + Week 16

Secondary outcomes (22)

  1. Effect of Arbaclofen vs. placebo on measures of global function

    CGI-I: Clinical Global Impression - Improvement Scale is used to determine the patient's improvement in response to treatment.

    Measured: Week 2 + Week 4 + Week 6 + Week 8 + Week 12 + Week 16 + Week 18

  2. Effect of Arbaclofen vs. placebo on measures of global function

    CGI-S: The Clinical Global Impression - Severity Scale is used to assess the impairment of neurobehavioral function in study subjects.

    Measured: Week 0 + Week 2 + Week 4 + Week 6 + Week 8 + Week 12 + Week 16 + Week 18

  3. Effect of Arbaclofen vs. placebo on other adaptive domains

    Vineland-3 (other adaptive domains): The Vineland Adaptive Behavior Scales, Third Edition, other adaptive domains: communication, daily living skills and motor skills.

    Measured: Week 0 + Week 16

  4. Effect of Arbaclofen on measures of social abilities and responsiveness

    ADOS-2: The Autism Diagnostic Observation Schedule, Version 2, will be used to assess autistic symptomatology.The ADOS-2 is a standardized protocol for the observation of social and communicative behaviour in children, adolescents, and adults who are suspected of having an ASD.

    Measured: Week -3

  5. Effect of Arbaclofen on measures of social abilities and responsiveness through BOSCC

    BOSCC: The Brief Observation of Social Communication Change will be used to to sensitively measure change of core autistic symptoms by observation of a semi-structured social interaction between a child and an examiner.

    Measured: Week 0 + Week 16

  6. Effect of Arbaclofen on measures of social abilities and responsiveness through SRS-2-P

    SRS-2-P: The Social Responsiveness Scale (parent version) measures the severity of social impairment in ASD.

    Measured: Week 0 + Week 16

  7. Effect of Arbaclofen on measures of social abilities and responsiveness through SRS-2-T

    SRS-2-T: The Social Responsiveness Scale (teacher version) measures the severity of social impairment in ASD.

    Measured: Week 0 + Week 16

  8. Effect of Arbaclofen on measures of problem behaviours

    ABC-C: This is the community version of the original residential version of the Aberrant Behaviour Checklist. It is designed to objectively identify five behaviour subscales through observation by the primary caregiver: irritability, lethargy, stereotypy, hyperactivity, and inappropriate speech.

    Measured: Week 0 + Week 4 + Week 8 + Week 12 + Week 16

  9. Effect of Arbaclofen on measures of problem behaviours

    CBCL: Child Behaviour Checklist is a caregiver report form identifying problem behaviour in children.

    Measured: Week 0 + Week 16

  10. Effect of Arbaclofen on other measures of core symptoms

    AIM: The Autism Impact Measure is designed to measure change in the core symptoms of autism.

    Measured: Week 0 + Week 4 + Week 8 + Week 12 + Week 16

  11. Safety and tolerability of Arbaclofen in children and adolescents with ASD as assessed with the SMURF

    SMURF: Safety Monitoring Uniform Research Form.

    Measured: Week 0 + Week 2 + Week 4 + Week 6 + Week 8 + Week 12 + Week 16 + Week 18

  12. Safety and tolerability of Arbaclofen in children and adolescents with ASD as assessed with the ESS-CHAD

    ESS-CHAD: The Epworth Sleepiness Scale for Children and Adolescents will be employed to evaluate sedation.

    Measured: Week 0 + Week 2 + Week 4 + Week 6 + Week 8 + Week 12 + Week 16 + Week 18

  13. Safety and tolerability of Arbaclofen in children and adolescents with ASD as assessed with the C-SSRS

    C-SSRS: The Columbia Suicide Severity Rating Scale is used to measure suicidality.

    Measured: Week 0 + Week 2 + Week 4 + Week 6 + Week 8 + Week 12 + Week 16 + Week 18

  14. Safety and tolerability of Arbaclofen in children and adolescents with ASD as assessed with a pulse rate measurement

    Vital signs: pulse

    Measured: Week -3 + Week 0 + Week 2 + Week 4 + Week 6 + Week 8 + Week 12 + Week 16 + Week 18

  15. Safety and tolerability of Arbaclofen in children and adolescents with ASD as assessed with a body temperature measurement

    Vital signs: body temperature

    Measured: Week -3 + Week 0 + Week 2 + Week 4 + Week 6 + Week 8 + Week 12 + Week 16 + Week 18

  16. Safety and tolerability of Arbaclofen in children and adolescents with ASD as assessed with a blood pressure measurement

    Vital signs: blood pressure

    Measured: Week -3 + Week 0 + Week 2 + Week 4 + Week 6 + Week 8 + Week 12 + Week 16 + Week 18

  17. Safety and tolerability of Arbaclofen in children and adolescents with ASD as assessed by measuring weight

    Weight: Weight (in kg) will be assessed with all outer wear and shoes removed.

    Measured: Week -3 + Week 0 + Week 2 + Week 4 + Week 6 + Week 8 + Week 12 + Week 16 + Week 18

  18. Safety and tolerability of Arbaclofen in children and adolescents with ASD as assessed by measuring height

    Height: Height (in cm) will be assessed with all outer wear and shoes removed.

    Measured: Week -3 + Week 0 + Week 2 + Week 4 + Week 6 + Week 8 + Week 12 + Week 16 + Week 18

  19. Safety and tolerability of Arbaclofen in children and adolescents with ASD as assessed with the Tanner scale

    Tanner stage

    Measured: Week -3 + Week 0 + Week 2 + Week 4 + Week 6 + Week 8 + Week 12 + Week 16 + Week 18

  20. Safety and tolerability of Arbaclofen in children and adolescents with ASD as assessed with blood tests

    Blood tests: CBC, serum chemistry, liver enzymes and renal function.

    Measured: Week -3 + Week 16

  21. Safety and tolerability of Arbaclofen in children and adolescents with ASD as assessed with blood tests

    Urine tests: basic urinalysis, toxics (amphetamines, benzodiazepines, barbiturates, marijuana/cannabis, cocaine, opioids (narcotics)) and pregnancy.

    Measured: Drug testing: Week -3 + Week 16, Pregnancy testing: Week -3 + Week 0 + Week 4 + Week 8 + Week 12 + Week 16

  22. To explore the use and feasibility of digital biomarkers

    To explore the use and feasibility of digital biomarkers as treatment-responsive measures of core and associated symptoms of ASD

    Measured: Week -3 + Week 0 + Week 2 + Week 4 + Week 6 + Week 8 + Week 12 + Week 16

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Sep 2018
  2. Study start19 Sep 2019
  3. Primary completion27 Jan 2023
  4. Study completion27 Jan 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
124 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03682978
Sponsor's protocol ID
AIMS2-CT-01
Other IDs
2018-000942-21, 2018
Acronym
AIMS2-CT1
Status last verified
Feb 2023
First submitted
7 Sep 2018
Last updated
8 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Parellada M, San Jose Caceres A, Delorme R, Moscoso A, Moreno C, Calvo R, Canal-Bedia R, Franco Martin MA, Charman T, Strydom A, Parr JR, Urbiola Merino E, Burdeus-Olavarrieta M, Hernandez Jusdado P, Solis A, Lucas M, Sipos L, Gonzalez Navarro P, Blazquez A, Lazaro L, Tomas A, Humeau E, Antoun S, Cooke J, Megalogeni M, Liang H, de-Vena-Diez VB, Leonard H, White N, Wang P, Walton-Bowen K, Winter-van Rossum I, Murphy D, Arango C. Efficacy, safety, and tolerability of arbaclofen in Autistic children and adolescents, the AIMS-2-TRIALS-CT1: a randomized, double-blind, placebo-controlled phase II trial. EClinicalMedicine. 2026 Jan 22;92:103760. doi: 10.1016/j.eclinm.2026.103760. eCollection 2026 Feb.

    PubMed 41631164

  • Parellada M, San Jose Caceres A, Palmer M, Delorme R, Jones EJH, Parr JR, Anagnostou E, Murphy DGM, Loth E, Wang PP, Charman T, Strydom A, Arango C. A Phase II Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety, and Tolerability of Arbaclofen Administered for the Treatment of Social Function in Children and Adolescents With Autism Spectrum Disorders: Study Protocol for AIMS-2-TRIALS-CT1. Front Psychiatry. 2021 Aug 24;12:701729. doi: 10.3389/fpsyt.2021.701729. eCollection 2021.

    PubMed 34504446

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Arbaclofen in people with Autism Spectrum Disorder, run by Celso Arango, MD, PhD at 7 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Spain, United Kingdom, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Effect of Arbaclofen vs. placebo on social function (time frame: Week 0 + Week 16). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03682978, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.

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