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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 September 2022
• Main ID: NCT03848832
• Date of registration: 19/02/2019
• Prospective Registration: Yes
• Primary sponsor: Jazz Pharmaceuticals
• Public title: Efficacy and Safety of Cannabidiol Oral Solution (GWP42003-P, CBD-OS) in Patients With Rett Syndrome ARCH
• Scientific 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
• Date of first enrolment: July 29, 2019
• Target sample size: 29
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03848832
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Italy, Spain, United Kingdom, United States

Key inclusion & exclusion 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.



Age minimum: 2 Years
Age maximum: 18 Years
Gender: All

Health Condition(s) or Problem(s) studied

Rett Syndrome

RTT

Intervention(s)

Drug: Placebo

Drug: GWP42003-P

Primary Outcome(s)

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 [Time Frame: Baseline; Week 24]

Secondary Outcome(s)

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 [Time Frame: Baseline; Week 24]

Change From Baseline in Mean Children's Sleep Habits Questionnaire (CSHQ) Total Score and Subscale Scores at Week 24 [Time Frame: Baseline; Week 24]

Change From Baseline in Mean 9-items Motor Behavioral Assessment (MBA-9) Total Score and Subscale Scores at Week 24 [Time Frame: Baseline; Week 24]

Mean Clinical Global Impressions - Improvement (CGI-I) Score at Week 24 [Time Frame: Baseline; Week 24]

Change From Baseline in Mean Clinician Global Impressions - Severity (CGI-S) Score at Week 24 [Time Frame: Baseline; Week 24]

Change From Baseline in Mean RSBQ Subscale Scores at Week 24 [Time Frame: Baseline; Week 24]

Secondary ID(s)

GWND18064

2018-003370-27

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 29/12/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03848832