Rett syndrome (RTT) [typical or atypical] MedDRA version: 20.0 Level: PT Classification code 10077709 Term: Rett syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: CBD - Oral Solution, is known as Epidyolex, and is the approved name
in the USA.
Product Name: Cannabidiol (CBD)
Product Code: GWP42003-P
Pharmaceutical Form: Oral solution
INN or Proposed
Sponsors
GW Research Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: For inclusion in the trial, patients must fulfil ALL of the following criteria: • Patient is female or male aged 2–18 years (inclusive). • Patient must weigh at least 10 kg. • Patient (if possessing adequate understanding, in the investigator’s opinion) and/or the patient's parent(s)/legal representative is willing and able to give informed consent/assent for participation in the trial. • Patient and the patient's 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). • Patient must have a clinical diagnosis of RTT (typical or atypical), defined according to RettSearch Consortium criteria. • Patient must have a confirmed pathogenic genetic mutation of the MECP2 gene. • Patient must be post-regression (= 6 months since last loss of hand use or verbal language or gross motor regression). • Patient must have a disease severity of between 10 and 36, defined according to the CSS. • All medications or interventions (including antiepileptic drugs [AEDs] and non-pharmacological interventions - dietary supplements, probiotics, physical therapy, speech therapy, etc.) for RTT-related symptoms must have been stable for 4 weeks prior to screening and the patient/caregiver should be willing to maintain a stable regimen throughout the trial. • Patient must have the ability to swallow the IMP provided as a liquid solution, or the ability for IMP to be delivered via gastrostomy (G) or nasogastric (NG) feeding tube (use of G-or NG-tubes is only allowed after discussion with the Medical Monitor to confirm suitability of the tubes being used). • Patient 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. • Patient and/or parent(s)/legal representative is willing to allow the patient’s primary care practitioner (if the patient has one) and consultant (if the patient has one) to be notified of participation in the trial, if the primary care practitioner/consultant is different to the investigator. Are the trial subjects under 18? yes Number of subjects for this age range: 252 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: The patient may not enter the trial if ANY of the following apply: • Patient meets exclusion criteria for RTT diagnosis (traumatic brain injury, neurometabolic disease, or severe infection that causes neurological problems; grossly abnormal psychomotor development in the first 6 months of life). • Patient has clinically significant abnormal laboratory values, in the investigator’s opinion. • Patient experiences more than weekly seizures (based on history over the last 2 months prior to screening) i.e., CSS ‘epilepsy/seizure’ score of 4 or 5. • Patient is taking more than 2 concurrent AEDs. • Any history of suicidal behavior or any suicidal ideation in the last month or at screening. • Patient has clinically relevant abnormalities in the ECG measured at screening or randomization (including QT interval, corrected by Bazett's correction formula [QTcB] interval > 450 msec, average of 3 measurements). • Patient has any concurrent cardiovascular conditions which will, in the investigator’s opinion, interfere with the ability to assess the patient's ECGs or put the patient at risk because of participation in the trial. • Patient’s first or second degree relative has a history of significant ECG abnormalities, in the opinion of the investigator (e.g. premature cardiac arrest, sudden death). • Patient has any known or suspected hypersensitivity to cannabinoids or any of the excipients of the IMP (active or placebo), such as sesame oil. • Patient has moderately impaired hepatic function at screening, defined as serum ALT or AST > 3 × ULN or total bilirubin [TBL] > 2 × ULN. This criterion can only be confirmed once the Visit 1 laboratory results are available. • Female patient 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 contraceptives, contraception a 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. • Female patient is pregnant (positive pregnancy test) or lactating. • Male patient is fertile (i.e., after puberty unless permanently sterile by bilateral orchiectomy) and with a partner of childbearing potential unless agree to ensure that they use male contraception (e.g., condom) or remain sexually abstinent during the trial and for 3 months after the last dose. • Patient has received an IMP within the 3 months prior to the screening visit. • Patient has been taking felbamate for less than 1 year prior to screening. • Patient is 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. • Patient has a positive ?9-tetrahydrocannabinol (THC) test at screening. • Patient has 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 patient, other participants, or site staff at risk because of participation in the trial, may influence the result of t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of 15 mg/kg/day GWP42003-P, compared with placebo, at the end of 24 weeks’ treatment in reducing symptom severity in patients with RTT using the Rett Syndrome Behaviour Questionnaire (RSBQ).;Secondary Objective: Secondary Objectives: - To evaluate the efficacy of 15 mg/kg/day GWP42003-P, compared with placebo, at the end of 24 weeks' treatment in reducing symptom severity in patients with RTT using the CGI-I. - To evaluate the efficacy of 5 mg/kg/day GWP42003-P, compared with placebo in: RSBQ, CGI-I. - To evaluate the effect of GWP42003-P, compared with placebo, in other measures of disease severity: RSBQ subscales, CGI-S, MBA-9, CSHQ. - To evaluate the safety of GWP42003-P, compared with placebo, in patients with RTT. Exploratory Objectives: - To evaluate the effect of GWP42003-P on caregiver and patient QoL: SF-36 and CHQ-PF50. - To evaluate the effect of GWP42003-P on HSUQ. - Caregiver assessment of Rett symptoms (symptom diary). -To determine the plasma concentrations of CBD and its major metabolites with the aim of evaluating exposure versus efficacy and safety and collecting data for population PK analysis. -To evaluate the effect of GWP42003-P on exploratory biomarkers. ;Primary end point(s): RSBQ (total score) for the 15 mg/kg/day GWP42003-P dose level compared with placebo at the end of 24 weeks.;Timepoint(s) of evaluation of this end point: Visit 2, Visit 5, Visit 6, Visit 7, Visit 8, Visit 9 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): CGI-I for the 15 mg/kg/day GWP42003-P dose level compared with placebo at the end of 24 weeks. Other Secondary Efficacy Endpoints: • To compare 5 mg/kg/day GWP42003-P with placebo using: o RSBQ (total score) o CGI-I • To compare 15 mg/kg/day GWP42003-P and 5 mg/kg/day GWP42003-P with placebo using: o RSBQ subscales. o CGI-S. o MBA-9. o CSHQ. Exploratory endpoints: • Caregiver QoL questionnaire (SF-36). • Patient QoL questionnaire (CHQ-PF50) • Hospital Services Use Questionnaire. • Caregiver assessment of Rett symptoms (symptom diary). • Plasma concentrations of CBD and its main metabolites. • Blood levels of exploratory biomarkers. Safety: The safety profile of GWP42003-P compared with placebo will be assessed by measuring: • AEs. • Clinical laboratory parameters. • Vital signs. • Physical examination procedures. • 12-lead electrocardiogram (ECG). • Effects on menstruation cycles. • Suicidality. • Change in growth and development by measurement of height, weight, serum insulin-like growth factor-1 (IGF-1) levels and Tanner Staging (for patients aged = 7 years, or earlier if clinically indicated by onset of menarche or other signs of precocious puberty).;Timepoint(s) of evaluation of this end point: Please refer to Protocol schedule of events table for detailed information | — |
Countries
Australia, Canada, France, Italy, Spain, United Kingdom, United States
Contacts
Public ContactGW Research Ltd Switchboard
GW Research Ltd
Outcome results
None listed