CBDV vs Placebo in Children and Adults up to Age 30 With Prader-Willi Syndrome (PWS)

Cannabidivarin (CBDV) vs. Placebo in Children and Adults up to Age 30 With Prader-Willi Syndrome (PWS)

This study aims to examine the feasibility and safety of cannabidivarin (CBDV) as a treatment for children and young adults with PWS.

Study Overview

• Status: Active, not recruiting
• Conditions: Prader-Willi Syndrome
• Intervention / Treatment: Drug: CBDV Compound; Drug: Placebo

Detailed Description

This clinical research trial aims to study the feasibility and safety of cannabidivarin (CBDV), in children and young adults with Prader-Willi Syndrome (PWS). CBDV has effects independent of CB1 and CB2 receptor activation and a good safety profile. This proposal addresses the Foundation for Prader Willi Research's PWS Research Plan: Program 1, Clinical Care Research: seeks to evaluate treatments that aim to reduce behavioral symptoms, such as irritability, in order to improve the quality of life of both the individual with PWS and their families. GW Pharmaceuticals will provide the CBDV drug and matching placebo.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bonnie Taylor, PhD; Phone Number: 718-839-7530; Email: botaylor@montefiore.org
• Study Contact Backup: Name: Alyssa Josselsohn; Phone Number: 718-839-7520; Email: alayssa.josselsohn@einsteinmed.edu

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center, Albert Einstein College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 30 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

1. Male or Female outpatients aged 5 to 30 years.
2. Diagnosis of PWS confirmed by genetic testing and patient medical records and history.
3. Stable pharmacologic, educational, behavioral and/or dietary interventions for 4 weeks prior to the study start, and for the duration of the study.
4. Have a physical exam and laboratory results that are within the norms for PWS
5. Presence of a parent/caregiver/guardian that is able to consent for their participation and complete assessments regarding the patient'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.
6. Score on the Clinical Global Impression Scale Severity (CGI-S) ≥ 4 (moderate severity) at baseline.
7. Score of ≥18 on the Aberrant Behavior Checklist-Irritability (ABC-I) at baseline.
8. Agree not to drive or operate machinery.

Exclusion Criteria

1. Exposure to any investigational agent in the 30 days prior to randomization.
2. Prior chronic treatment with CBD or CBDV.
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. History of Drug Abuse Disorder including Cannabis Use Disorder
5. A primary psychiatric diagnosis other than PWS, including bipolar disorder, psychosis, schizophrenia, PTSD or MDD. These patients will be excluded due to potential confounding results.
6. 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 (including but not limited to hepatic or renal impairment and cardiovascular disease).
7. Known or suspected allergy to CBDV or excipients used in the formulation (i.e. sesame).
8. Clinical indications of renal, pancreatic, or hematologic dysfunction as evidenced by values above upper limits of normal for BUN/creatinine, values twice the upper limit of normal for serum lipase and amylase, platelets <80,000 /mcL, WBC<3.0 103 /mcL. or > 2 X UNL values of AST or ALT.
9. ECG abnormality at baseline screening or clinically significant postural drop in systolic blood pressure at screening. If the initial screening ECG shows 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
10. 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 pregnancy test before entry into the study. Female subjects will be informed not 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cannabidivarin (CBDV); Weight-based dosing of 10 mg/kg/day of CBDV for 12 weeks	Drug: CBDV Compound; CBDV is obtained from the Cannabis sativa L. plant and contains a negligible quantity (less than 0.2%) of THC
Placebo Comparator: Matched Placebo; Weight-based dosing of 10 mg/kg/day of placebo for 12 weeks	Drug: Placebo; Placebo oral solution contains matching excipients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aberrant Behavior Checklist-Irritability Subscale (ABC-I)	Change in the ABC-I score. The ABC-I is a well-characterized outcome that is accepted by the FDA for the purpose of labeling, and is one of the best and most validated outcome measures in the developmental disabilities. An inclusion cutoff of 18 or higher on the ABC-I at screening was chosen based on multiple medication trials with irritability as the primary target.	from Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Repetative Behavior Scale- Revised (RBS-R)	Change in RBS-R score (a 44-item self-report questionnaire that is used to measure the breadth or repetitive behaviors)	from Baseline to Week 12
Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS)	Change in the CY-BOCS score. The CY-BOCS is 10-item clinician measure designed to assess the severity of obsessive compulsive symptoms in children and adolescents over the previous week. It consists of four primary sections including Obsessions checklist, Severity items for Obsessions, Compulsions checklist and severity items for Compulsions and a set of investigational items. Improvement on this scale was associated with improvements in caregiver quality of life in our 8-week study of intranasal oxytocin.	from Baseline to Week 12
Hyperphagia Questionnaire for Clinical Trials (HQ-CT)	Change in HQ-CT score. The HQ-CT is a 9-item caregiver-reported measure of food-seeking behaviors that was used in the phase 3 beloranib trial.	from Baseline to Week 12
ActiGraph GT9X-BT activity monitors	Change in Sleep Behaviors. Actigraph activity monitors are a well validated activity sleep monitoring device that has been utilized widely in clinical trials and health research, measuring sleep latency, total sleep time, and sleep efficiency.	from Baseline to Week 12
Clinical Global Impression Scale - Improvement (CGI-I)	The CGI-I will be used as a measure of improvement and contains a 7 point scale as follows: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, 7 = very much worse. The CGI-I is a clinician rated global measure of improvement and has been used as a measure in previous clinical psychopharmacology trials.	from Baseline to Week 12
Caregiver Strain Questionnaire (CSQ)	The Caregiver Strain questionnaire is a 21-item self-report questionnaire that was developed to assess caregiver strain for families with a child living with an emotional or behavioral disorder.	from Baseline to Week 12
Montefiore Einstein Rigidity Scale-Revised-PWS (MERS-R-PWS)	The Montefiore-Einstein Rigidity Scale-Revised-PWS (MERS-R-PWS) is designed to assess three domains of rigid behavior in individuals with PWS: Behavioral Rigidity (e.g., Insistence on sameness, things must be done in his/her way, etc.); Cognitive Rigidity (e.g., Special interests, inflexible adherence to rules, etc.); Protest (in response to deviation from rigidity; e.g., tantrum, irritability, arguing) The MERS-R-PWS is a clinician-rated scale and takes about 20 minutes to complete. It will be completed only for subjects who display rigid behaviors at baseline, week 4, week 8 and week 12.	from Baseline to Week 12
Aberrant Behavior Checklist (ABC) subscales in lethargy/social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech	The ABC is an informative rating instrument that was empirically derived by principal component analysis to measure behavior in those with developmental disability and ASD. It contains 58 items that resolve into 5 subscales. The subscales and the respective number of items are as follows: (a) irritability - 15 items, (b) lethargy/social withdrawal - 16 items, (c) stereotypic behavior - 7 items, (d) hyperactivity/noncompliance - 16 items, and (e) inappropriate speech - 4 items. The ABC was designed to be completed by any adult who knows the patient well, such as a parent/caregiver or teacher. This instrument measures behavior on a four-point severity scale where 0 = no problem at all, 1 = behavior is a problem but in a slight degree, 2 = problem is moderately serious, and 3 = problem is severe in degree.	from Baseline to Week 12

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Collaborators: Jazz Pharmaceuticals; Foundation for Prader-Willi Research
• Investigators: Principal Investigator: Eric Hollander, MD, Montefiore Medical Center/Albert Einstein College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2020
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: February 19, 2019
• First Submitted That Met QC Criteria: February 19, 2019
• First Posted (Actual): February 20, 2019

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 22, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: CBDV; Irritability; PWS; Cannabinoids; Prader- Willi Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Overnutrition; Nutrition Disorders; Overweight; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Obesity; Syndrome; Prader-Willi Syndrome
• Other Study ID Numbers: 2019-9914

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All IPD that underlie results in a publication

Drug and device information, study documents

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