A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of Balovaptan in Children With Autism Spectrum Disorder

A Phase Ib, Multicenter, Open-Label, 6-Week Study With a 48-Week Extension to Investigate the Pharmacokinetics, Safety, and Tolerability of Balovaptan in Children Ages 2-4 Years With Autism Spectrum Disorder

This was a Phase Ib, multicenter, open-label study in children 2-4 years old with autism spectrum disorder (ASD) to investigate the pharmacokinetics, safety, and tolerability of an oral dose of balovaptan once a day (QD). The study was to consists of a 6-week treatment period to evaluate the pharmacokinetics of balovaptan in 2 to 4 year old children followed by an optional extension period of 48 weeks.

Study Overview

• Status: Terminated
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Drug: Balovaptan

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Southwest Autism Research & Resource Center
  • New York
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center; Division of Child and Adolescent Psychiatry
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77090
      • Red Oak Psychiatry Associates, PA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 4 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of ASD according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for ASD. Diagnostics will be performed by a team of autism experts and confirmed by Autism Diagnostic Observation ScheduleTM, Second Edition (ADOS-2) criteria. The DSM-5 criteria for diagnosis of autism must be met with the highest confidence in the opinion of the investigator. Children with ambiguous diagnostic results cannot be enrolled in the study. If the ADOS-2 assessment has been performed by a certified rater and documented within 12 months of the screening visit, it is not mandatory to repeat it unless the subject was assessed below an age of 2 years.
• Hearing and vision compatible with the study assessments, as judged by the investigator
• Ability for subject and the caregiver to comply with the study protocol, in the investigator's judgment
• Availability of a parent or other reliable caregiver who is fluent in language of the site and has frequent and sufficient contact with the subject.

Exclusion Criteria:

• Clinically significant psychiatric and/or neurologic comorbidity that may interfere with the safety or efficacy endpoints in the view of the investigator
• Clinically significant regression of any acquired language and motor function skills in the opinion of the investigator throughout the subject's development
• History of seizures with the exception of a single, non-complicated febrile seizure >= 6 months before screening
• Clinical diagnosis of peripheral neuropathy or signs and symptoms indicative of peripheral neuropathy
• Any clinically relevant cardiovascular disease
• Confirmed elevation in cardiac troponin I (cTn I), high-sensitive cardiac troponin T (hs cTn T), N-terminal pro-B-type natriuretic peptide (NT-proBNP) or, if conducted, clinically relevant abnormality in Doppler echocardiogram
• Confirmed clinically significant abnormality on ECG at screening, including, but not limited to, a QT interval corrected through use of Fridericia's formula (QTcF) of >= 450 ms, absence of dominating sinus rhythm, or second- or third-degree atrioventricular block
• Confirmed systolic or diastolic blood pressure above the 95th percentile or below the 5th percentile according to the Centers for Disease Control and Prevention (CDC) norm tables referring to stature (height)-for-age percentiles
• Confirmed heart rate: >150 bpm in 2-year old children, >135 bpm in 3-year old children, or >120 bpm in 4-year old children.
• Concomitant disease or condition that could interfere with, or treatment of which might interfere with, the conduct of the study; or discontinuation of prohibited medication that might pose unacceptable risks to the subject in the opinion of the investigator
• Evidence for current GI disease that would interfere with the conduct of the study or pose unacceptable risks in the opinion of the investigator
• History of coagulopathies, bleeding disorders, or blood dyscrasias
• Positive serology for HIV-1 or HIV-2
• Confirmed clinically significant abnormality in parameters of hematology, clinical chemistry, coagulation, or urinalysis, specifically a confirmed absolute neutrophil count (ANC) <LLN Children with confirmed CPK elevations exceeding 2 x upper limit of normal (ULN) will be excluded
• History of malignancy
• Clinically significant loss of blood within 3 months prior to screening
• Unstable use of permitted medications for 4 weeks before screening
• Use of prohibited medications within 30 days (or 5 times the half-life, whichever is longer) prior to initiation of study treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Balovaptan	Drug: Balovaptan; Participants were to receive an oral dose of balovaptan once a day (QD) for a 6-week treatment period, followed by an optional extension period of 48 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Curve at Steady State (AUCss) of Balovaptan	Predose, 2, 4, 6 hours postdose at Week 2; predose at Week 6; predose at Week 12; predose at Week 24, predose at Week 54
Plasma Concentration of Balovaptan	Predose, 2, 4, 6 hours postdose at Week 2; predose at Week 6; predose at Week 12; predose at Week 24, predose at Week 54
Plasma Concentration of M2 Metabolite, as Applicable	Predose, 2, 4, 6 hours postdose at Week 2; predose at Week 6; predose at Week 12; predose at Week 24, predose at Week 54
Plasma Concentation of M3 Metabolite	Predose, 2, 4, 6 hours postdose at Week 2; predose at Week 6; predose at Week 12; predose at Week 24, predose at Week 54
Plasma Concentration Ratio of M2 to Balovaptan, as Applicable	Predose, 2, 4, 6 hours postdose at Week 2; predose at Week 6; predose at Week 12; predose at Week 24, predose at Week 54
Plasma Concentration Ratio of M3 to Balovaptan	Predose, 2, 4, 6 hours postdose at Week 2; predose at Week 6; predose at Week 12; predose at Week 24, predose at Week 54

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events	Up to approximately week 20

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2019
• Primary Completion (Actual): April 23, 2020
• Study Completion (Actual): May 6, 2020

Study Registration Dates

• First Submitted: August 6, 2019
• First Submitted That Met QC Criteria: August 6, 2019
• First Posted (Actual): August 8, 2019

Study Record Updates

• Last Update Posted (Actual): October 14, 2020
• Last Update Submitted That Met QC Criteria: September 21, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
• Other Study ID Numbers: WP40877

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No