Cannabidivarin (CBDV) vs. Placebo in Children With Autism Spectrum Disorder (ASD)

• ClinicalTrials.gov Identifier: NCT03202303
• Recruitment Status: Recruiting
• First Posted: June 28, 2017
• Last Update Posted: September 22, 2022
• Sponsor: Montefiore Medical Center
• Collaborators: United States Department of Defense; Jazz Pharmaceuticals
• Information provided by (Responsible Party): Montefiore Medical Center

Tracking Information

• First Submitted Date: June 27, 2017
• First Posted Date: June 28, 2017
• Last Update Posted Date: September 22, 2022
• Actual Study Start Date: April 12, 2019
• Estimated Primary Completion Date: July 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 27, 2017)

Aberrant Behavior Checklist-Irritability Subscale (ABC-I) [ Time Frame: Change in ABC-I from Baseline to Week 12 (Change over 12 weeks) ]

Change in ABC-I from Baseline to Endpoint

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 21, 2020)

• Repetitive Behavior Scale-Revised (RBS-R) [ Time Frame: Change in RBS-R from Baseline to Week 12 (Change over 12 weeks) ]
  Change in RBS-R from Baseline to Endpoint
• Aberrant Behavior Checklist-Social Withdrawal Subscale (ABC-SW) [ Time Frame: Change in ABC-SW from Baseline to Week 12 (Change over 12 weeks) ]
  Change in ABC-SW from Baseline to Endpoint
• Pediatric Quality of Life Inventory (PedsQL) Family Impact Module [ Time Frame: Change in PedsQL from Baseline to Week 12 (Change over 12 weeks) ]
  Change in PedsQL from Baseline to Endpoint
• Vineland Adaptive Behavior Scale-3 (Vineland 3) [ Time Frame: Change in Vineland-3 from Baseline to Week 12 (Change over 12 weeks) ]
  Change in Vineland-3 from Baseline to Endpoint
• Clinical Global Impressions-Improvement (CGI-I) [ Time Frame: Change in CGI-I from Baseline to Week 12 (Change over 12 weeks) ]
  Change in CGI-I from Baseline to Endpoint
• Montefiore Einstein Rigidity Scale-Revised (MERS-R) [ Time Frame: Change in MERS-R from Baseline to Week 12 (Change over 12 weeks) ]
  The MERS-R is designed to assess three domains of rigid behavior in children and adults with ASD: 1. Behavioral Rigidity (e.g., insistence on sameness, things must be done in his/her way, etc.) 2. Cognitive Rigidity (e.g., special interests, inflexible adherence to rules, etc.) 3. Protest (in response to deviation from rigidity; e.g., verbal objection, tantrum, physical aggression).

Original Secondary Outcome Measures (submitted: June 27, 2017)

• Repetitive Behavior Scale-Revised (RBS-R) [ Time Frame: Change in RBS-R from Baseline to Week 12 (Change over 12 weeks) ]
  Change in RBS-R from Baseline to Endpoint
• Aberrant Behavior Checklist-Social Withdrawal Subscale (ABC-SW) [ Time Frame: Change in ABC-SW from Baseline to Week 12 (Change over 12 weeks) ]
  Change in ABC-SW from Baseline to Endpoint
• Pediatric Quality of Life Inventory (PedsQL) Family Impact Module [ Time Frame: Change in PedsQL from Baseline to Week 12 (Change over 12 weeks) ]
  Change in PedsQL from Baseline to Endpoint
• Vineland Adaptive Behavior Scale-II (VABS-II) [ Time Frame: Change in VABS-II from Baseline to Week 12 (Change over 12 weeks) ]
  Change in VABS-II from Baseline to Endpoint
• Clinical Global Impressions-Improvement (CGI-I) [ Time Frame: Change in CGI-I from Baseline to Week 12 (Change over 12 weeks) ]
  Change in CGI-I from Baseline to Endpoint

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cannabidivarin (CBDV) vs. Placebo in Children With Autism Spectrum Disorder (ASD)
• Official Title: Cannabidivarin (CBDV) vs. Placebo in Children With Autism Spectrum Disorder (ASD)
• Brief Summary: This trial aims to study the efficacy and safety of cannabidivarin (CBDV) in children with ASD.

Detailed Description

There is a clear unmet need for new therapeutics to treat irritability in children with ASD that do not have the metabolic and weight adverse event profiles of the currently approved treatments. Cannabidivarin (CBDV) is a nonpsychoactive phytocannabinoid and a safe variant of Cannabidiol (CBD). It has no appreciable tetrahydrocannabinol (THC) [less than 0.01%], has been shown to have no impact on weight or metabolism, and improves both social and cognitive functioning in animal models of idiopathic and syndromal autism (Fragile X, Rett Syndrome, Angelman Syndrome). The CDC currently estimates 1 in 59 children have ASD. ASD is characterized by deficits in social communication, irritability, repetitive behaviors, impulsivity, temper tantrums, and high caregiver burden. Currently, the only FDA-approved medications for symptoms of ASD are aripiprazole and risperidone, both of which are indicated for irritability in pediatric ASD. These medications are effective but are associated with considerable side effects with long term treatment in this chronic developmental disorder, including weight gain, metabolic syndrome and the risk of type 2 diabetes, prolactin elevation and growth of breast tissue, extrapyramidal symptoms and the risk of tardive dyskinesia. The anticonvulsant divalproex sodium (valproate/VPA) also significantly reduces irritability and repetitive behaviors in individuals with ASD. Although VPA is efficacious for pediatric epilepsy and some symptoms of ASD, it also has significant side effects, including weight gain, sedation and nausea. CBDV, like VPA, is effective in the treatment of pediatric epilepsy, and ASD mouse models demonstrate potential mechanisms for treatment with CBDV, including potential therapeutic effects on repetitive behaviors, irritability, sociability, and quality of life, and the capacity to reduce inflammation. This study aims to examine the efficacy and safety of cannabidivarin (CBDV) with a primary aim of studying its effect on irritability in children with ASD.

STUDY DESIGN: This is a 12-week randomized, double-blind study of CBDV vs. placebo in 100 child and adolescent subjects aged 5 to 18 years with a diagnosis of ASD.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Phase 2, 12-week double-blind, randomized, placebo-controlled trial

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double-Blind

Primary Purpose: Treatment

• Condition: Autism Spectrum Disorder

Intervention

• Drug: Cannabidivarin
  Weight-based dosing of 10 mg/kg/day of CBDV
  Other Name: CBDV
• Drug: Matched Placebo
  Weight-based dosing of 10 mg/kg/day of placebo
  Other Name: Placebo

Study Arms

• Experimental: Cannabidivarin (CBDV)
  Weight-based dosing of 10 mg/kg/day of CBDV for 12 weeks
  Intervention: Drug: Cannabidivarin
• Placebo Comparator: Matched Placebo
  Weight-based dosing of 10 mg/kg/day of placebo for 12 weeks
  Intervention: Drug: Matched Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 27, 2017): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 31, 2023
• Estimated Primary Completion Date: July 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria

1. Male or Female pediatric outpatients aged between and including ages 5 to 18. Diagnosis of Autism Spectrum Disorder (ASD) confirmed by the ADOS-2 and DSM-5 criteria.*During special circumstances (e.g. COVID-19 pandemic) where the ADOS-2 cannot be performed due to site restrictions (e.g. mandatory use of face masks), eligibility can be confirmed using the Autism Diagnostic Interview, Revised (ADI-R)
2. Aberrant Behavior Checklist (ABC) - Irritability Subscale (ABC-I) score of 18 or greater at screening visit.
3. Social Responsiveness Scale (SRS) score of 66T or higher at screening visit.
4. Clinical Global Impression Scale - Severity (CGI-S) score of 4 or higher at screening.
5. Stable pharmacologic, educational, behavioral and/or dietary interventions for 4 weeks prior to randomization and for the duration of the study.
6. Physical exam and laboratory results that are within normal range for individuals with ASD.
7. Presence of a parent/caregiver/guardian that is able to consent for their participation and complete assessments regarding the child's development and behavior throughout the study. Child Assent will be obtained if the subject is 7 years of age or older and has the mental capacity to understand and sign a written assent form and/or give verbal assent.

Exclusion Criteria

1. Exposure to any investigational agent in the 30 days prior to randomization.
2. Prior chronic treatment with CBD, CBDV or an endocannabinoid treatment.
3. Positive testing for THC or other drugs of abuse via urine testing at the screening visit or baseline visits upon repeat confirmation testing.
4. Recent history of drug abuse including marijuana/cannabis use in the past 3 months.
5. Diagnosis of a known genetic disorder (ie. Prader-Willi Syndrome, Angelman Syndrome etc.).
6. A primary psychiatric diagnosis other than ASD, including bipolar disorder, psychosis, schizophrenia, Post-Traumatic Stress Disorder (PTSD) or Major Depressive Disorder (MDD). These patients will be excluded due to potential confounding results.
7. A medical condition that severely impacts the subject's ability to participate in the study, interferes with the conduct of the study, confounds interpretation of study results or endangers the subject's well-being.
8. A known diagnosis of Rett Syndrome or Childhood Disintegrative Disorder, or marked sensory impairment such as deafness or blindness.
9. Subjects who have had changes in allied health therapies, behavioral or educational interventions within four weeks prior to randomization other than those associated with school holidays.
10. Subjects who have had changes in medications or medication doses within four weeks of randomization. Renal, pancreatic, or hematologic dysfunction as evidenced by values above upper limits of normal for BUN/creatinine, or values twice the upper limit of normal for serum lipase and amylase, platelets <80,000 /mcL, or WBC<3.0 103 /mcL
11. Liver dysfunction manifested by > 2 X UNL values of AST or ALT
12. ECG abnormality at baseline screening or clinically significant postural drop in systolic blood pressure at screening. If the initial screening ECG show a QTcB of greater than 460 msec, then 2 additional ECGs will be conducted in the same sitting, 5 minutes apart. If not recognized at screening, then a full triplicate repeat showing an average QTcB of 460 msec or less to meet all inclusion/exclusion criteria. Female subjects who are pregnant will be excluded from the study. If a female subject is able to become pregnant, she will be given a serum pregnancy test before entry into the study. Female subjects will be informed not to become pregnant while taking CBDV. Female subjects must tell the investigator and consult an obstetrician or maternal-fetal specialist if they become pregnant during the study.
13. Known allergy to sesame oil

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 5 Years to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Bonnie P Taylor, PhD; 718-839-7530; botaylor@montefiore.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03202303
• Other Study ID Numbers: 2017-8538; AR160104 ( Other Grant/Funding Number: Department of Defense (DOD) ); G32379 ( Other Grant/Funding Number: GW Pharmaceuticals )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Montefiore Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Montefiore Medical Center
• Original Study Sponsor: Same as current

Collaborators

• United States Department of Defense
• Jazz Pharmaceuticals

Investigators

• Principal Investigator: Eric Hollander, MD; Montefiore Medical Center/Albert Einstein College of Medicine

• PRS Account: Montefiore Medical Center
• Verification Date: September 2022