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

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT04049578
• Collaborator: (none)
• Enrollment: 2
• Locations: 5
• Arm: 1
• Actual Duration (Months): 4.6
• Patients Per Site: 0.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Autism Spectrum Disorder	Drug: Balovaptan	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Dec 19, 2019
• Actual Primary Completion Date: Apr 23, 2020
• Actual Study Completion Date: May 6, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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]

2. 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]

3. 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]

4. 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]

5. 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]

6. 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

1. Number of Participants With Adverse Events [Up to approximately week 20]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 4 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southwest Autism Research & Resource Center	Phoenix	Arizona	United States	85006
2	Richmond Behavioral Associates	Staten Island	New York	United States	10312
3	University Hospitals Cleveland Medical Center; Division of Child and Adolescent Psychiatry	Cleveland	Ohio	United States	44106
4	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
5	Red Oak Psychiatry Associates, PA	Houston	Texas	United States	77090

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 8, 2019

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT04049578
• Other Study ID Numbers: WP40877
• First Posted: Aug 8, 2019
• Last Update Posted: Oct 14, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive

Study Results

Participant Flow

Arm/Group Title	Balovaptan
Arm/Group Description	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.
Period Title: Overall Study
STARTED	2
COMPLETED	1
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Balovaptan
Arm/Group Description	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.
Overall Participants	2
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	3.45 (0.78)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	2 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 50%
Not Hispanic or Latino	1 50%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	2 100%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Area Under the Curve at Steady State (AUCss) of Balovaptan
Time Frame	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

Outcome Measure Data

Analysis Population Description

Due to low enrollment number patient analysis are not provided to protect participant confidentiality.

Arm/Group Title	Balovaptan
Arm/Group Description	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.
Measure Participants	0

2. Primary Outcome

Title	Plasma Concentration of Balovaptan
Time Frame	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

Outcome Measure Data

Analysis Population Description

Due to low enrollment number patient analysis are not provided to protect participant confidentiality.

Arm/Group Title	Balovaptan
Arm/Group Description	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.
Measure Participants	0

3. Primary Outcome

Title	Plasma Concentration of M2 Metabolite, as Applicable
Time Frame	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

Outcome Measure Data

Analysis Population Description

Due to low enrollment number patient analysis are not provided to protect participant confidentiality.

Arm/Group Title	Balovaptan
Arm/Group Description	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.
Measure Participants	0

4. Primary Outcome

Title	Plasma Concentation of M3 Metabolite
Time Frame	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

Outcome Measure Data

Analysis Population Description

Due to low enrollment number patient analysis are not provided to protect participant confidentiality.

Arm/Group Title	Balovaptan
Arm/Group Description	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.
Measure Participants	0

5. Primary Outcome

Title	Plasma Concentration Ratio of M2 to Balovaptan, as Applicable
Time Frame	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

Outcome Measure Data

Analysis Population Description

Due to low enrollment number patient analysis are not provided to protect participant confidentiality.

Arm/Group Title	Balovaptan
Arm/Group Description	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.
Measure Participants	0

6. Primary Outcome

Title	Plasma Concentration Ratio of M3 to Balovaptan
Time Frame	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

Outcome Measure Data

Analysis Population Description

Due to low enrollment number patient analysis are not provided to protect participant confidentiality.

Arm/Group Title	Balovaptan
Arm/Group Description	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.
Measure Participants	0

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Balovaptan
Arm/Group Description	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.
Measure Participants	2
Number [Number of Participants]	2 100%

Adverse Events

Time Frame	From the first study drug to the data cutoff date: 6 May 2020 (up to approximately 20 weeks)
Adverse Event Reporting Description	The safety population is defined as patients who received any amount of study treatment.
Arm/Group Title	Balovaptan
Arm/Group Description	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.
All Cause Mortality
	Balovaptan
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Serious Adverse Events
	Balovaptan
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Balovaptan
	Affected / at Risk (%)	# Events
Total	2/2 (100%)
Investigations
Blood thyroid stimulating hormone increased	1/2 (50%)	1
Metabolism and nutrition disorders
Abnormal weight gain	1/2 (50%)	1
Nervous system disorders
Psychomotor hyperactivity	1/2 (50%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/2 (50%)	1
Vascular disorders
Haematoma	1/2 (50%)	1

Limitations/Caveats

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

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.