Arbaclofen in Children and Adolescents With ASD

• Status: Recruiting
• Trial end date: 2022-08-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Celso Arango, MD, PhD; Inge Winter
• Collaborators: Hospital General Universitario Gregorio Marañon; UMC Utrecht
• Treatments: Baclofen

Criteria

Inclusion Criteria:

1. Signed Written Informed Consent

1. 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.

2. Participants must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.

3. 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.

4. 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.

2. Type of Participant and Target Disease Characteristics

1. Diagnosis of an Autism Spectrum Disorder according to the DSM-5 criteria

2. Complex language as defined in ADOS-2 to qualify for a Module 3 or 4.

3. 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

4. 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).

5. 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.

3. Age, Residential and Reproductive Status

1. Male or female participants 5 to 17 years of age at the time of providing consent, inclusive.

2. Reside with the parent/carer who is interviewed for the Vineland.

3. Negative pregnancy test for females of childbearing potential (subject has experienced onset of menses) within 24h prior to study treatment starts.

4. 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).

5. 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.

Exclusion Criteria:

1. 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.

2. Prior/Concomitant Therapy

1. 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.

2. 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.

3. 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.

4. Subjects who have taken another investigational drug within the last 30 days.

3. 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.

4. Study Medication Related

1. Subjects who are not able to take oral medications.

2. Subjects who have a history of hypersensitivity to racemic baclofen.

3. Subjects with rare hereditary problems of galactose intolerance, the lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4. Active peptic ulceration as Baclofen stimulates gastric acid secretion.

5. Porphyria.

5. Other Exclusion Criteria

1. Subjects who are currently engaged in illicit drug use or alcohol abuse, according to DSM-5 criteria.

2. Subjects who have previously participated in a clinical trial of Arbaclofen.

3. Women who are breastfeeding.