Arbaclofen in Children and Adolescents With ASD

NCT03682978 | Completed Phase 2 DMC

• 2 other identifiers: AIMS2-CT-012018-000942-21
• Study Type: interventional
• Target: 124
• Locations: 3 countries
• Sites: 7

Brief 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. 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.

Conditions

Autism Spectrum Disorder

Keywords

Arbaclofen; Placebo-Controlled; Randomized; Double-Blind; Social Function; Efficacy; Safety; Tolerability; Children; Adolescents; ASD

Outcome Measures

Primary Outcomes (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.

  Week 0 + Week 16

Secondary Outcomes (22)

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

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

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

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

• Effect of Arbaclofen vs. placebo on other adaptive domains

  Week 0 + Week 16

• Effect of Arbaclofen on measures of social abilities and responsiveness

  Week -3

• Effect of Arbaclofen on measures of social abilities and responsiveness through BOSCC

  Week 0 + Week 16

Other Outcomes (7)

• Explore whether P1 & N170 amplitude & latency as measures of electrophysiology (EEG) are associated with either response to treatment

  Week 0 + Week 16

• Explore whether Alpha & Theta power (frontal) and Theta connectivity as measures of electrophysiology (EEG) are associated with either response to treatment

  Week 0 + Week 16

• Explore whether induced power at 10Hz & 40Hz as measures of electrophysiology (EEG) are associated with either response to treatment

  Week 0 + Week 16

Study Arms (2)

Arbaclofen

EXPERIMENTAL

Arbaclofen 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.

Drug: Arbaclofen

Placebo

PLACEBO COMPARATOR

Placebo 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.

Drug: Placebo

Interventions

Arbaclofen DRUG

Arbaclofen tablet.

Also known as: R-4-amino-3-(4-chlorophenyl) butanoic acid (R-baclofen), STX209, C10H12ClNO2

Arbaclofen

Placebo DRUG

Placebo tablet.

Also known as: Placebo (for Arbaclofen)

Placebo

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• 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.

You may not qualify if:

• Medical Conditions
• a. 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.
• Subjects who have taken another investigational drug within the last 30 days.
• Physical and Laboratory Test Findings
• a. 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.

Sponsors & Collaborators

• Celso Arango, MD, PhD: lead
• UMC Utrecht: collaborator

Study Sites (7)

Robert Debré Hospital

Paris, 75019, France

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

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

Madrid, 28009, Spain

Location

University of Salamanca & Complejo asistencial de Zamora

Salamanca, Spain

Location

University of Glasgow

Glasgow, G78 1SL, United Kingdom

Location

King's College London

London, SE5 8AF, United Kingdom

Location

University of Newcastle upon Tyne

Newcastle, NE1 7RU, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 41631164 DERIVED

• 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.

  PMID: 34504446 DERIVED

Related Links

• AIMS-2-TRIALS website

MeSH Terms

Conditions

Autism Spectrum Disorder; Social Adjustment

Interventions

arbaclofen placarbil; Butyric Acid

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Social Behavior; Behavior

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Celso Arango, Prof.

  Hospital General Universitario Gregorio Marañón

  STUDY CHAIR

• Mara Parellada, Prof.

  Hospital General Universitario Gregorio Marañón

  PRINCIPAL INVESTIGATOR

• Richard Delorme, Prof.

  Hopital Universitaire Robert-Debre

  PRINCIPAL INVESTIGATOR

• Jeremy Parr, Prof.

  University of Newcastle Upon-Tyne

  PRINCIPAL INVESTIGATOR

• Mallika Punukollu, Dr.

  University of Glasgow

  PRINCIPAL INVESTIGATOR

• Andre Strydom, Prof.

  King's College London

  PRINCIPAL INVESTIGATOR

• Rosa Calvo, Dr.

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: AIMS2-CT-01 is a double-blind study where participants and parent(s)/legal guardians as well as research staff will be unaware of the treatment allocation, with the exception of a dedicated unblinded pharmacist at each individual site. Blinding of the remainder of the study team members will be maintained by utilizing identical tablets, blistercards and boxes containing either Arbaclofen or placebo. Unblinded study drug and placebo supplies will be stocked at each study site pharmacy. An online randomization system will be used, by this unblinded pharmacist, to assign the study treatment. Based on the outcome of the randomisation, the pharmacist prepares the boxes containing the applicable treatment and releases these (blinded) boxes to the investigator for dispensing to the patient. In order to maintain the study blind, the dosing regimen will be consistent whether participants are randomized to Arbaclofen or placebo.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2018
• First Posted: September 25, 2018
• Study Start: September 19, 2019
• Primary Completion: January 27, 2023
• Study Completion: January 27, 2023
• Last Updated: February 8, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); ES (3); GB (3)