AzTrials
AzTrials

Autism Spectrum DisorderPhase 2NCT02901431

A Study to Investigate the Efficacy and Safety of Balovaptan (RO5285119) in Participants With Autism Spectrum Disorder (ASD)

A Phase 2 study testing RO5285119 in people with Autism Spectrum Disorder, run by Hoffmann-La Roche at 45 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

For participants enrolled prior to Version 6 of the protocol: This was a Phase II multi-center, randomized, double-blind, 24-week, 3-arm, parallel group, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of balovaptan in children and adolescents aged 5-17 years with ASD who are high… Read more about this study

Who is it for?
Ages 5 to 17 years
Conditions the study is for
Autism Spectrum Disorder
What is being tested?
RO5285119
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
339 participants
Where
45 sitesUnited States
Study dates
21 Nov 2016to 30 Jun 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 5 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Fluent in English
  • Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for ASD or International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD10) criteria for Autism diagnosis confirmed by Autism Diagnostic Observational Schedule (ADOS-2) criteria
  • Social Responsiveness Scale, second edition (SRS-2) (T-score) >= 66
  • Clinical Global Impressions of Severity (CGI-S) >= 4 (moderately ill) at screening
  • IQ >= 70 as assessed by Wechsler Abbreviated Scale of Intelligence Scale: Second Edition (WASI-II) or Wechsler Preschool and Primary Scale of Intelligence: Fourth Edition (WPPSI-IV) intelligence test
  • Language, hearing, and vision compatible with the study measurements as judged by the investigator
  • Have completed the blinded treatment phase of the study OR were required to stop dosing at or before Week 8
  • Have no adverse events that would prohibit starting the OLE

Who cannot join

  • Initiation of a major change in psychosocial intervention (including investigational) within 4 weeks prior to screening
  • Unstable or uncontrolled clinically significant psychiatric and/or neurological disorder that may interfere with the safety or efficacy endpoints
  • Known personal or family history of cerebral aneurysm
  • Risk of suicidal behavior
  • Seizure within the past 6 months
  • Medical history of alcohol or substance abuse/dependence
Show all 18Show fewer
  • Concurrent cardio-vascular disease not considered well controlled by the Investigator
  • Clinically significant abnormality on electrocardiogram at screening
  • Concomitant disease or condition (pulmonary, gastro-intestinal, hepatic, renal, metabolic, immunological system, or obesity that could interfere with the conduct of the study
  • Evidence for current gastro-intestinal bleeding, e.g., active stomach ulcer disease
  • History of coagulopathies, bleeding disorders, or blood dyscrasias
  • Positive serology for hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) 1, or HIV 2
  • Confirmed clinically significant abnormality in parameters of hematology, clinical chemistry, coagulation, or urinalysis
  • Medical history of malignancy if not considered cured
  • Participation in an investigational drug study within 90 days or 5 times the half-life of the investigational molecule (whichever is longer) prior to randomization
  • Loss of blood over 250 milliliters within three months prior to screening
  • Allowed medications have not been stable since 4 weeks before screening, and allowed medications for treatment of epilepsy have not been stable since 3 months before screening
  • Use of prohibited medications within 2 weeks prior to screening visit or 5 times the half-life prior to randomization (whichever is longer)

Trial locations and contacts

45 sites in 1 country.

45 sites in 1 country

United States45 sites

  • Children's Hospital of Colorado

    Aurora, Colorado, 80045

  • BioBehavioral Research of Austin, PC

    Austin, Texas, 78759

  • Kennedy Krieger Institute

    Baltimore, Maryland, 21205

  • Northwest Clinical Research Center

    Bellevue, Washington, 98007

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Boston Childrens Hospital

    Boston, Massachusetts, 02115

  • Pacific Institute of Medical Sciences

    Bothell, Washington, 98011

  • DBA IMMUNOe Int'l Res Center

    Centennial, Colorado, 80112

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • University Hospitals

    Cleveland, Ohio, 44106

  • Ohio State University

    Columbus, Ohio, 43210

  • Relaro Medical Trials

    Dallas, Texas, 75243

  • Harmonex Neuroscience Research

    Dothan, Alabama, 36303

  • DUKE SCHOOL OF MEDICINE;Duke Center for Autism and Brain Development

    Durham, North Carolina, 27705

  • Core Clinical Research

    Everett, Washington, 98201

  • Sarkis Clinical Trials

    Gainesville, Florida, 32607

  • Red Oak Psychiatry Associates, PA

    Houston, Texas, 77090

  • Massachusetts General Hospital; Lurie Center for Autism

    Lexington, Massachusetts, 02421

  • Capstone Clinical Research

    Libertyville, Illinois, 60048

  • Midwest Childrens Health Research Institute

    Lincoln, Nebraska, 68516

  • Suburban Research Associates

    Media, Pennsylvania, 19063

  • University of Minnesota; Clin. Neuro Research Unit

    Minneapolis, Minnesota, 55414

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Yale University / Yale-New Haven Hospital

    New Haven, Connecticut, 06519-1124

  • Center for Autism and the Developing Brain

    New York, New York, 10032

  • Segal trials

    North Miami, Florida, 33161

  • Cutting Edge Research Group

    Oklahoma City, Oklahoma, 73116

  • NRC Research Institute

    Orange, California, 92868

  • Medical Research Group of Central Florida

    Orange City, Florida, 32763

  • Nathan S. Kline Institute for Psychiatric Research

    Orangeburg, New York, 10962

  • APG- Advanced Psychiatric Group

    Orlando, Florida, 32803

  • Children's Hospital of Philadelphia;Allergy/Immunology Department

    Philadelphia, Pennsylvania, 19104

  • Southwest Autism Research & Resource Center

    Phoenix, Arizona, 85006

  • UPMC Western Psychiatric Institute and Clinic

    Pittsburgh, Pennsylvania, 15203

  • University of Rochester

    Rochester, New York, 14627 0001

  • St. Charles Psychiatric Associates

    Saint Charles, Missouri, 63304

  • Road Runner Research

    San Antonio, Texas, 78249

  • PCSD Feighner Research

    San Diego, California, 92108

  • University of California at San Francisco

    San Francisco, California, 94115

  • Seattle Children's Research Institute; Psychiatry and Behavioral Medicine

    Seattle, Washington, 98121

  • USF Rothman Center

    St. Petersburg, Florida, 33701

  • Richmond Behavioral Associates

    Staten Island, New York, 10312

  • Albert Einstein College of Medicine

    The Bronx, New York, 10461

  • UMASS Medical School

    Worcester, Massachusetts, 01655

Other trials in United States

About this study

Official title: A Phase II Multi-Center, Randomized, Double-Blind, 24-Week, Parallel Group, Placebo-Controlled Study to Investigate the Efficacy and Safety of Balovaptan (RO5285119) in Children and Adolescents Age 5-17 With Autism Spectrum Disorder (ASD)

For participants enrolled prior to Version 6 of the protocol: This was a Phase II multi-center, randomized, double-blind, 24-week, 3-arm, parallel group, placebo-controlled study to investigate the efficacy, safety, and pharmacokinetics of balovaptan in children and adolescents aged 5-17 years with ASD who are high functioning (intelligence quotient [IQ] greater than or equal to [>=] 70).

For participants enrolled according to Version 6 of the protocol: This was a Phase II multi-center, randomized, double-blind, 24-week, parallel group, placebo-controlled, 2-arm study with participants assigned either to a 10 milligram (mg) or equivalent dose of balovaptan, or placebo. All other study parameters remained as stated above.

Read more

There are three parts to this study: PK Part (Study part 1) included up to 8 weeks of treatment, Main Treatment Part (Study part 2) included 24 week of treatment, and the Open Label Extension Part (Study part 3) included Week 24 to Week 76 of treatment.

All participants that completed the 24-week treatment period were eligible to participate in an optional 52-week open-label extension (OLE) during which they received balovaptan treatment.

Being tested
Placebo, RO5285119
Medical subject headings
Autism Spectrum Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    Participants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.

  • RO5285119Drug

    Participants received age-adjusted total daily oral dose approximately equivalent to the adult doses of either 4 mg/d or 10 mg/d of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks (up to 52 additional weeks for those enrolled in the OLE).

Study groups in NCT02901431
Study groupRoleWhat they receive
PlaceboPlacebo comparatorParticipants received a matching placebo orally. Approximate treatment duration was up to 24 weeks.
Receives: Drug: Placebo
Balovaptan (RO5285119) 10 mg/d equivalentExperimentalParticipants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 10 milligrams per day (mg/d) of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks (up to 52 additional weeks for those enrolled in the OLE).
Receives: Drug: RO5285119
Balovaptan (RO5285119) 4 mg/d equivalentExperimentalParticipants received age-adjusted total daily oral dose approximately equivalent to the adult dose of 4 mg/d of balovaptan (RO5285119). Approximate treatment duration was up to 24 weeks. This arm is open only to those participants enrolled prior to Version 6 of the study protocol.
Receives: Drug: RO5285119

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change From Baseline in Vineland™-II Adaptive Behavior Scale Two Domain Composite (2DC) Score at Week 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

    Vineland™-II Adaptive Behavior Scales 2-Domain Composite (2DC) Score is defined as mean of the Communication domain standard score \& Socialization domain standard score. If any of the 2 individual domain standard scores is missing 2DC score is not computed. Vineland™-II is an instrument that measures communication, daily living skills, socialization, motor skills and maladaptive behavior of individuals with developmental disabilities. Survey Interview Form will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning. Mixed model with repeated measures (MMRM) was used for analysis with assessments at baseline, week 12 and week 24.

    Measured: Baseline, Week 24

Secondary outcomes (11)

  1. Change From Baseline in Vineland™-II Composite Standard Score After 12 Weeks and 24 Weeks of Treatment for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

    The Vineland™-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills (up to 6 years only) and used to calculate the Vineland-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning.

    Measured: Baseline, Weeks 12 and 24

  2. Change From Baseline in Vineland™-II Adaptive Behavior Scale Communication, Socialization, and Daily Living Skills Domain Standard Scores at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

    The Vineland™-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, and Daily Living Skills. Standardized scores on the domains range from 20-160 with higher scores indicating better functioning. Measure Type is Adjusted least-squares means.

    Measured: Baseline, Weeks 12 and 24

  3. Proportion of Subjects With >=6 Points Improvement in the Vineland-II 2DC Score for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

    Vineland™-II Adaptive Behavior Scales 2-Domain Composite (2DC) Score is defined as mean of the Communication domain standard score \& Socialization domain standard score. If any of the 2 individual domain standard scores is missing 2DC score is not computed. Vineland™-II is an instrument that measures communication, daily living skills, socialization, motor skills and maladaptive behavior of individuals with developmental disabilities. Survey Interview Form will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills and used to calculate the Vineland™-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning.

    Measured: Baseline, Weeks 12 and 24

  4. Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

    The CGI-S reflects the rater's impression of the subject's current autism severity on a 7-point scale ranging from no symptoms (1) to very severe symptoms (7). Changes in CGI-S score were calculated as increase or decrease in absolute CGI-S scores between Baseline and Weeks 12 and 24.

    Measured: Baseline, Weeks 12 and 24

  5. Change From Baseline in Ohio Autism Clinical Impressions Scale-Severity (OACIS-S) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

    The OACIS-S is a 10-item, clinician-completed measures based upon interview and/or observation. The OACIS-S assess severity and improvement, respectively, in social interaction, aberrant behavior, repetitive or ritualistic behavior, verbal communication, nonverbal communication skills, hyperactivity and inattention, anxiety and fearfulness, sensory sensitivities, restricted and narrow interests, and a global rating of autism. Each item of the OACIS-S is rated on a 7-point scale ranging from no symptoms (1) to very severe symptoms (7). Changes in CGI-S score were calculated as increase or decrease in absolute CGI-S scores between Baseline and Weeks 12 and 24.

    Measured: Baseline, Weeks 12 and 24

  6. Clinical Global Impressions- Improvement (CGI-I) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

    The CGI rating scales are tools used to evaluate both the severity of illness and change from baseline. The CGI-I is used to assess the clinical change as compared to symptoms at baseline using a 7-point scale, ranging from very much improved (1) to very much worse (7). For this study modified versions will be used.

    Measured: Weeks 12 and 24

  7. Ohio Autism Clinical Impressions Scale- Improvement (OACIS-I) Score at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

    The OACIS-I is a 10-item, clinician-completed measures based upon interview and/or observation. The OACIS-I assess severity and improvement, respectively, in social interaction, aberrant behavior, repetitive or ritualistic behavior, verbal communication, nonverbal communication skills, hyperactivity and inattention, anxiety and fearfulness, sensory sensitivities, restricted and narrow interests, and a global rating of autism. The OACIS-I is used to assess the clinical change as compared to symptoms at baseline using a 7-point scale, ranging from very much improved (1) to very much worse (7).

    Measured: Weeks 12 and 24

  8. Change From Baseline in Patient-Reported Pediatric Quality of Life (PedsQL) v4.0 Generic Core Scale After 12 Weeks and 24 Weeks of Treatment for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

    The Pediatric Quality of Life Inventory PedsQL™4.0 Generic Core Scale assessment consists of a 23 item questionnaire encompassing 4 core scale domains: Physical Functioning (8 items); Emotional Functioning (5 items); Social Functioning (5 items); and School Functioning (5 items). For children aged 8 years and above, the PedsQL items are scored on a 5 point Likert-type response scale (0=never a problem; 1=almost never a problem; 2=sometimes a problem; 3=often a problem; and 4=almost always a problem). For children aged 5-7 years, scoring is based on a three-point scale (0=Not at all, 2=Sometimes, 4=A lot). Once scored, items will be reverse scored and linearly transformed to a 0-100 scale (0=100, 1=75, 2=50, 3=25, 4=0), so that higher scores indicate better health-related quality of life.

    Measured: Baseline, Weeks 12 and 24

  9. Change From Baseline in Vineland-II Composite Standard Score in Adolescents and Children Independently at Weeks 12 and 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

    The Vineland-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills (up to 6 years only) and used to calculate the Vineland-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning.

    Measured: Baseline, Weeks 12 and 24

  10. Change From Baseline in Vineland-II Adaptive Behavior Scale 2DC Score at Week 12 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo

    The Vineland-II is an instrument that measures communication, daily living skills, socialization, motor skills (only in children up to 6 years) and maladaptive (not assessed in this study) behavior of individuals with developmental disabilities. The Survey Interview Form (i.e., semi -structured interview) will be administered to a subject's reliable caregiver in this study, during which the rater or clinician will ask to the caregiver open ended questions relating to the subject's activities and behavior. Domain scores will be obtained for the individual domains of Socialization, Communication, Daily Living Skills, and motor skills (up to 6 years only) and used to calculate the Vineland-II Adaptive Behavior Composite score. Standardized scores on the Adaptive behavior composite range from 20-160 with higher scores indicating better functioning. Mixed model with repeated measures (MMRM) was used for analysis.

    Measured: Baseline, Week 12

  11. Percentage of Participants With Adverse Events for Treatment With Balovaptan

    PK review revealed that age-adjusted doses of 4 and 10 mg in 5-17 year olds were not equivalent to target exposure. For the Main Study Part, data was summarised by exposure ranges (tertiles) based on individual participants PK exposure at Week 12, estimated as the average plasma concentration since treatment start. To allow clear analysis by exposure tertiles, participants with dose adjustment were excluded from analysis by tertiles.

    Measured: Baseline to Week 24 and up to Week 76

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Sep 2016 (estimated)
  2. Study start21 Nov 2016
  3. Primary completion15 Apr 2020
  4. Study completion30 Jun 2020

Why it stopped: The 24-week analysis indicated no clinical or statistical benefit for the primary endpoint for the overall study population. No new safety concerns identified.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
339 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02901431
Sponsor's protocol ID
BP30153
Status last verified
Jan 2021
First submitted
12 Sep 2016
Last updated
8 Feb 2021

Publications

  • Hollander E, Jacob S, Jou R, McNamara N, Sikich L, Tobe R, Smith J, Sanders K, Squassante L, Murtagh L, Gleissl T, Wandel C, Veenstra-VanderWeele J. Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Aug 1;79(8):760-769. doi: 10.1001/jamapsychiatry.2022.1717.

    PubMed 35793101

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RO5285119 in people with Autism Spectrum Disorder, run by Hoffmann-La Roche at 45 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 45 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Vineland™-II Adaptive Behavior Scale Two Domain Composite (2DC) Score at Week 24 for Balovaptan (R05285119) 10 mg Equivalent Compared to Placebo (time frame: Baseline, Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02901431, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in