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

NCT04049578 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: WP40877
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Autism Spectrum Disorder

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (1)

• Number of Participants With Adverse Events

  Up to approximately week 20

Study Arms (1)

Balovaptan

EXPERIMENTAL

Drug: Balovaptan

Interventions

Balovaptan DRUG

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.

Balovaptan

Eligibility Criteria

• Age: 2 Years - 4 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (5)

Southwest Autism Research & Resource Center

Phoenix, Arizona, 85006, United States

Location

Richmond Behavioral Associates

Staten Island, New York, 10312, United States

Location

University Hospitals Cleveland Medical Center; Division of Child and Adolescent Psychiatry

Cleveland, Ohio, 44106, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Red Oak Psychiatry Associates, PA

Houston, Texas, 77090, United States

Location

MeSH Terms

Conditions

Autism Spectrum Disorder

Interventions

balovaptan

Condition Hierarchy (Ancestors)

Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Limitations and Caveats

Study was terminated with 2 participants enrolled. Due to low enrollment number patient analysis are not provided to protect participant confidentiality.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2019
• First Posted: August 8, 2019
• Study Start: December 19, 2019
• Primary Completion: April 23, 2020
• Study Completion: May 6, 2020
• Last Updated: October 14, 2020
• Results First Posted: October 14, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)