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

• ClinicalTrials.gov Identifier: NCT03848481
• Recruitment Status: Recruiting
• First Posted: February 20, 2019
• Last Update Posted: December 22, 2022
• Sponsor: Montefiore Medical Center
• Collaborators: Foundation for Prader-Willi Research; Jazz Pharmaceuticals
• Information provided by (Responsible Party): Eric Hollander, Montefiore Medical Center

Study Description

Brief Summary:

This trial aims to study the efficacy and safety of cannabidivarin (CBDV) as a treatment for children with PWS.

Condition or disease	Intervention/treatment	Phase
Prader-Willi Syndrome	Drug: CBDV Compound; Drug: Placebo	Phase 2

Detailed Description:

This clinical research trial aims to study the efficacy and safety of cannabidivarin (CBDV), a naturally occurring homolog of the phytocannabinoid cannabidiol (CBD) 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 five year 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 and additional funding to the site.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Cannabidivarin (CBDV) vs. Placebo in Children and Adults up to Age 30 With Prader-Willi Syndrome (PWS)
• Actual Study Start Date: November 23, 2020
• Estimated Primary Completion Date: December 2023
• Estimated Study Completion Date: December 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Aberrant Behavior Checklist-Irritability Subscale (ABC-I) [ Time Frame: from Baseline to Week 12 ]
   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.

Secondary Outcome Measures :

1. Repetative Behavior Scale- Revised (RBS-R) [ Time Frame: from Baseline to Week 12 ]
   Change in RBS-R score (a 44-item self-report questionnaire that is used to measure the breadth or repetitive behaviors)
2. Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) [ Time Frame: from Baseline to Week 12 ]
   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.
3. Hyperphagia Questionnaire for Clinical Trials (HQ-CT) [ Time Frame: from Baseline to Week 12 ]
   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.
4. ActiGraph GT9X-BT activity monitors [ Time Frame: from Baseline to Week 12 ]
   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.
5. Clinical Global Impression Scale - Improvement (CGI-I) [ Time Frame: from Baseline to Week 12 ]
   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.
6. Caregiver Strain Questionnaire (CSQ) [ Time Frame: from Baseline to Week 12 ]
   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.
7. Montefiore Einstein Rigidity Scale-Revised-PWS (MERS-R-PWS) [ Time Frame: from Baseline to Week 12 ]

   The Montefiore-Einstein Rigidity Scale-Revised-PWS (MERS-R-PWS) is designed to assess three domains of rigid behavior in individuals with PWS:

   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., 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.
8. Aberrant Behavior Checklist (ABC) subscales in lethargy/social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech [ Time Frame: from Baseline to Week 12 ]
   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

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

Contact: Alyssa Josselsohn; 718-839-7520; alayssa.josselsohn@einsteinmed.edu

Locations

United States, New York

Montefiore Medical Center, Albert Einstein College of Medicine; Recruiting

Bronx, New York, United States, 10467

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

Contact: Alyssa Josselsohn, PhD 718-839-7520 alyssa.josselsohn@einsteinmed.edu

Principal Investigator: Eric Hollander, MD

Sponsors and Collaborators

Montefiore Medical Center

Foundation for Prader-Willi Research

Jazz Pharmaceuticals

Investigators

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

More Information

• Responsible Party: Eric Hollander, Director, Autism and Obsessive Compulsive Spectrum Program, Anxiety and Depression Program, Montefiore Medical Center
• ClinicalTrials.gov Identifier: NCT03848481
• Other Study ID Numbers: 2019-9914
• First Posted: February 20, 2019
• Last Update Posted: December 22, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All IPD that underlie results in a publication

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

Keywords provided by Eric Hollander, Montefiore Medical Center:

PWS; Prader- Willi Syndrome; Irritability; CBDV; Cannabinoids

Additional relevant MeSH terms:

Prader-Willi Syndrome; Syndrome; Disease; Pathologic Processes; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Obesity; Overnutrition; Nutrition Disorders