Clinical trial NCT03848832: Efficacy and Safety of Cannabidiol Oral Solution (GWP42003-P, CBD-OS) in Patients With Rett Syndrome
Official title: A Randomized, Double-blind, Placebo-controlled Trial to Investigate the Efficacy and Safety of Cannabidiol Oral Solution (GWP42003-P, CBD-OS) in Patients With Rett Syndrome
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Rett Syndrome
RTT
Keywords: Cannabidiol
CBD
Epidiolex
GWP42003-P
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-02-21
Enrollment: 29
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

* 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.

Key Exclusion Criteria:

* Participant meets exclusion criteria for Rett syndrome diagnosis (traumatic brain injury, neurometabolic disease, or severe infection that causes neurological problems; grossly abnormal psychomotor development in the first 6 months of life).
* 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
* Any abnormalities identified following a physical examination of the participant that, in the opinion of the investigator, would jeopardize the safety of the participant if she took part in the trial
* Participant has been previously randomized into this trial.
* Participant has traveled outside the country of residence planned during the trial.

Primary outcomes:
measure: 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
timeFrame: Baseline; Week 24
Secondary outcomes:
measure: 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
timeFrame: Baseline; Week 24
measure: Mean Clinical Global Impressions - Improvement (CGI-I) Score at Week 24
timeFrame: Baseline; Week 24
measure: Change From Baseline in Mean Clinician Global Impressions - Severity (CGI-S) Score at Week 24
timeFrame: Baseline; Week 24
measure: Change From Baseline in Mean RSBQ Subscale Scores at Week 24
timeFrame: Baseline; Week 24
measure: Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24
timeFrame: Baseline; Week 24
measure: Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24
timeFrame: Baseline; Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Trial Site
state: Alabama
city: San Diego
country: United States
facility: Clinical Trial Site
state: California
city: Aurora
country: United States
facility: Clinical Trial Site
state: Colorado
city: Chicago
country: United States
facility: Clinical Trial Site
state: Illinois
city: Baltimore
country: United States
facility: Clinical Trial Site
state: Maryland
city: Boston
country: United States
facility: Clinical Trial Site
state: Massachusetts
city: Saint Paul
country: United States
facility: Clinical Trial Site
state: Minnesota
city: Saint Louis
country: United States
facility: Clinical Trial Site
state: Missouri
city: Bronx
country: United States
facility: Clinical Trial Site
state: New York
city: Cincinnati
country: United States
facility: Clinical Trial Site
state: Ohio
city: Philadelphia
country: United States
facility: Clinical Trial Site
state: Pennsylvania
city: Greenwood
country: United States
facility: Clinical Trial Site
state: South Carolina
city: Nashville
country: United States
facility: Clinical Trial Site
state: Tennessee
city: Houston
country: United States
facility: Clinical Trial Site
state: Texas
city: Genoa
country: Italy
facility: Clinical Trial Site
city: Messina
country: Italy
facility: Clinical Trial Site
city: Milan
country: Italy
facility: Clinical Trial Site
city: Rome
country: Italy
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Barcelona
country: Spain
facility: Clinical Trial Site
city: Madrid
country: Spain
facility: Clinical Trial Site
city: Madrid
country: Spain
facility: Clinical Trial Site
city: Valencia
country: Spain
facility: Clinical Trial Site
city: Liverpool
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
city: London
country: United Kingdom
facility: Clinical Trial Site
Study officials:
References: