Efficacy and Safety of Cannabidiol Oral Solution (GWP42003-P, CBD-OS) in Patients With Rett Syndrome

NCT03848832 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: GWND180642018-003370-27
• Study Type: interventional
• Target: 29
• Locations: 4 countries
• Sites: 26

Brief Summary

To evaluate the efficacy of cannabidiol oral solution (GWP42003-P, CBD-OS) in reducing symptom severity when compared with placebo, in participants with Rett syndrome.

Conditions

Rett Syndrome; RTT

Keywords

Cannabidiol; CBD; Epidiolex; GWP42003-P

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Mean Rett Syndrome Behaviour Questionnaire (RSBQ) Total Score at Week 24 for the 15 mg/kg/Day GWP42003-P Dose Level Compared With Placebo

  RSBQ is a caregiver-completed questionnaire that measures the frequency of current disease characteristics (45 items) in individuals with Rett Syndrome. Each item is rated on a 3-point scale (0-2); 0 indicating an item that is "not true as far as you know," 1 indicating an item is "somewhat or sometimes true," and 2 indicating an item that is "very true or often true." Item 31 ("Uses eye gaze to convey feelings, needs and wishes") is reverse scored (0 indicating "very true or often true", 1 indicating "somewhat or sometimes true," and 2 indicating "not true as far as you know"). The total summed score ranges from 0 to 90, with higher scores representing greater severity.

  Baseline; Week 24

Secondary Outcomes (6)

• Change From Baseline in the Mean RSBQ Total Score at Week 24 for the 5 mg/kg/Day GWP42003-P Dose Level Compared With Placebo

  Baseline; Week 24

• Mean Clinical Global Impressions - Improvement (CGI-I) Score at Week 24

  Baseline; Week 24

• Change From Baseline in Mean Clinician Global Impressions - Severity (CGI-S) Score at Week 24

  Baseline; Week 24

• Change From Baseline in Mean RSBQ Subscale Scores at Week 24

  Baseline; Week 24

• Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24

  Baseline; Week 24

Study Arms (3)

5 milligrams per kilogram per day (mg/kg/day) GWP42003-P

EXPERIMENTAL

100 milligrams per milliliter (mg/mL) GWP42003-P oral solution. Taken twice daily (morning and evening).

Drug: GWP42003-P

15 mg/kg/day GWP42003-P

EXPERIMENTAL

100 mg/mL GWP42003-P oral solution. Taken twice daily (morning and evening).

Drug: GWP42003-P

Placebo

PLACEBO COMPARATOR

Placebo oral solution (0 mg/mL GWP42003-P) volume matched to 5 mg/kg/day or 15 mg/kg/day GWP42003-P. Taken twice daily (morning and evening).

Drug: Placebo

Interventions

GWP42003-P DRUG

GWP42003-P presented as an oral solution containing cannabidiol

Also known as: Cannabidiol, CBD, Epidiolex, CBD-OS

15 mg/kg/day GWP42003-P; 5 milligrams per kilogram per day (mg/kg/day) GWP42003-P

Placebo DRUG

Matching placebo oral solution

Placebo

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participant (if possessing adequate understanding, in the investigator's opinion) and/or their parent(s)/legal representative is willing and able to give informed consent/assent for participation in the trial.
• Participant and their caregiver are willing and able (in the investigator's opinion) to comply with all trial requirements (including the completion of all caregiver assessments by the same caregiver throughout the trial).
• Participant must weigh at least 10 kilograms.
• Clinical diagnosis of Rett syndrome (typical or atypical), defined according to RettSearch Consortium criteria
• Confirmed pathogenic genetic mutation of the MECP2 gene
• Participant must be post-regression (≥ 6 months since last loss of hand use or verbal language or gross motor regression).
• Participant must have a disease severity of between 10 and 36, defined according to the Clinical Severity Scale (CSS).
• All medications or interventions (including antiepileptic drugs \[AEDs\] and non-pharmacological interventions - dietary supplements, probiotics, physical therapy, speech therapy, etc.) for Rett syndrome-related symptoms must have been stable for 4 weeks prior to screening and the participant/caregiver must be willing to maintain a stable regimen throughout the trial.
• Ability to swallow the investigational medicinal product (IMP) provided as a liquid solution, or the ability for IMP to be delivered via gastrostomy (G) or nasogastric (NG) feeding tube (only G-or NG-tubes made from polyurethane or silicon are allowed)
• Participant and/or parent(s)/legal representative is willing to allow the responsible authorities to be notified of participation in the trial, if mandated by local law.
• Participant and/or parent(s)/legal representative is willing to allow the participant's primary care practitioner (if they have one) and consultant (if they have one) to be notified of participation in the trial, if the primary care practitioner/consultant is different than the investigator.

You may not qualify if:

• Participant has clinically significant abnormal laboratory values, in the investigator's opinion.
• Participant is taking more than 2 concurrent AEDs.
• Any history of suicidal behavior or any suicidal ideation in the last month or at screening
• Clinically relevant abnormalities in the electrocardiogram (ECG) measured at screening or randomization
• Concurrent cardiovascular conditions which will, in the investigator's opinion, interfere with the ability to assess their ECGs or put the participant at risk because of participation in the trial
• First or second degree relative with a history of significant ECG abnormalities, in the opinion of the investigator (e.g. premature cardiac arrest, sudden death)
• Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP (active or placebo), such as sesame oil
• Participant has moderately impaired hepatic function at screening, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 × upper limit of normal (ULN) or total bilirubin \> 2 × ULN.
• Participant is of childbearing potential, unless willing to ensure that they or their partner use a highly effective method of birth control (e.g., combined \[estrogen and progestogen containing\] hormonal contraception associated with inhibition of ovulation \[oral, intravaginal, or transdermal\], progestogen-only hormonal contraception associated with inhibition of ovulation \[oral, injectable, or implantable\], intrauterine devices/hormone-releasing systems, bilateral tubal occlusion, vasectomized partner, sexual abstinence) during the trial and for 3 months thereafter.
• Pregnant (positive pregnancy test) or lactating
• Received an IMP within the 3 months prior to screening
• Participant has been taking felbamate for less than 1 year prior to screening.
• Currently using or has used recreational or medicinal cannabis, cannabinoid-based medications (including Sativex®), or cannabidiol oral solutions (including CBD-OS \[GWP42003-P\]) within the 3 months prior to screening and is unwilling to abstain for the duration of the trial
• Participant has a positive delta-9-tetrahydrocannabinol (THC) test at screening.
• Any other systemic dysfunction (e.g., gastrointestinal, renal, respiratory) or significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the trial, may influence the result of the trial, or the participant's ability to participate in the trial

Sponsors & Collaborators

• Jazz Pharmaceuticals: lead

Study Sites (26)

Clinical Trial Site

Birmingham, Alabama, 35294-0021, United States

Location

Clinical Trial Site

San Diego, California, 92123, United States

Location

Clinical Trial Site

Aurora, Colorado, 80045, United States

Location

Clinical Trial Site

Chicago, Illinois, 60612, United States

Location

Clinical Trial Site

Baltimore, Maryland, 21205, United States

Location

Clinical Trial Site

Boston, Massachusetts, 02115, United States

Location

Clinical Trial Site

Saint Paul, Minnesota, 55101, United States

Location

Clinical Trial Site

St Louis, Missouri, 63110-1093, United States

Location

Clinical Trial Site

The Bronx, New York, 10467, United States

Location

Clinical Trial Site

Cincinnati, Ohio, 45229, United States

Location

Clinical Trial Site

Philadelphia, Pennsylvania, 19104, United States

Location

Clinical Trial Site

Greenwood, South Carolina, 29646, United States

Location

Clinical Trial Site

Nashville, Tennessee, 37232, United States

Location

Clinical Trial Site

Houston, Texas, 77030, United States

Location

Clinical Trial Site

Genoa, 16147, Italy

Location

Clinical Trial Site

Messina, 98124, Italy

Location

Clinical Trial Site

Milan, 20142, Italy

Location

Clinical Trial Site

Rome, 00165, Italy

Location

Clinical Trial Site

Barcelona, 08022, Spain

Location

Clinical Trial Site

Barcelona, 08950, Spain

Location

Clinical Trial Site

Madrid, 28009, Spain

Location

Clinical Trial Site

Madrid, 28040, Spain

Location

Clinical Trial Site

Valencia, 46026, Spain

Location

Clinical Trial Site

Liverpool, L12 2AP, United Kingdom

Location

Clinical Trial Site

London, SE1 7EU, United Kingdom

Location

Clinical Trial Site

London, SE5 8BB, United Kingdom

Location

MeSH Terms

Conditions

Rett Syndrome

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Limitations and Caveats

This study was terminated early due to enrollment challenges and the Coronavirus disease-2019 (COVID-19) pandemic. Numbers of participants in each treatment groups were small, which precluded the planned formal statistical inferences and limited data interpretation.

Results Point of Contact

• Title: Medical Enquiries
• Organization: GW Research Ltd

medinfo@gbio.com

1-833-424-6724

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2019
• First Posted: February 21, 2019
• Study Start: July 29, 2019
• Primary Completion: January 21, 2021
• Study Completion: January 21, 2021
• Last Updated: September 2, 2022
• Results First Posted: December 29, 2021

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4); GB (3); ES (5); US (14)