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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03848832
Recruitment Status : Active, not recruiting
First Posted : February 21, 2019
Last Update Posted : November 17, 2020
Sponsor:
Information provided by (Responsible Party):
GW Research Ltd

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.

Condition or disease Intervention/treatment Phase
Rett Syndrome RTT Drug: GWP42003-P Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 252 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : July 29, 2019
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Rett Syndrome

Arm Intervention/treatment
Experimental: 5 milligrams per kilogram per day (mg/kg/day) GWP42003-P
100 milligrams per milliliter (mg/mL) GWP42003-P oral solution. Taken twice daily (morning and evening).
Drug: GWP42003-P
GWP42003-P presented as an oral solution containing cannabidiol in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Other Names:
  • Cannabidiol
  • CBD
  • Epidiolex
  • CBD-OS

Experimental: 15 mg/kg/day GWP42003-P
100 mg/mL GWP42003-P oral solution. Taken twice daily (morning and evening).
Drug: GWP42003-P
GWP42003-P presented as an oral solution containing cannabidiol in the excipients sesame oil and anhydrous ethanol with added sweetener (sucralose) and strawberry flavoring.
Other Names:
  • Cannabidiol
  • CBD
  • Epidiolex
  • CBD-OS

Placebo Comparator: Placebo
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
Placebo oral solution containing the excipients sesame oil and anhydrous ethanol with added beta-carotene, sweetener (sucralose) and strawberry flavoring.




Primary Outcome Measures :
  1. Rett Syndrome Behaviour Questionnaire (RSBQ) [ Time Frame: 24 weeks ]
    RSBQ is a caregiver-completed questionnaire that measures the frequency of current disease characteristics (45 items); each item rated on a 3-point scale (0-2). Higher scores represent greater severity.


Secondary Outcome Measures :
  1. Clinical Global Impressions - Improvement (CGI-I) [ Time Frame: 24 weeks ]
    CGI-I is a 7-point scale that requires the clinician to assess how much a participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention. (1 = very much improved, to 7 = very much worse.)

  2. RSBQ subscales [ Time Frame: 24 weeks ]
    The 45 items in the caregiver-completed RSBQ encompass 8 subscales: 1) general mood, 2) breathing problems, 3) hand behaviors, 4) face movements, 5) body rocking/expressionless face, 6) night-time behaviors, 7) anxiety/fear, 8) walking/standing. Higher scores represent greater severity.

  3. Clinician Global Impressions - Severity Scale (CGI-S) [ Time Frame: 24 weeks ]
    CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment relative to the clinician's experience with participants who have the same diagnosis, rating from 1 = normal, not at all ill, to 7 = extremely ill.

  4. 9-items Motor Behavioral Assessment (MBA-9) [ Time Frame: 24 weeks ]
    MBA-9 was derived from the full MBA scale (37 Rett syndrome symptoms) by selecting the items deemed amenable to change and which reflect areas of meaningful clinical change. The severity of current symptoms are rated by the investigator on a 5-point numerical scale, from 0 = normal or never, to 4 = very severe or constant. Higher total scores represent greater severity.

  5. Children's Sleep Habits Questionnaire (CSHQ) [ Time Frame: 24 weeks ]
    CSHQ is a caregiver-completed sleep screening instrument designed for school-aged children, including 33 items within 8 subscales reflecting the following sleep domains:1) bedtime resistance, 2) sleep onset delay, 3) sleep duration, 4) sleep anxiety, 5) night wakings, 6) parasomnias, 7) sleep-disordered breathing, 8) daytime sleepiness. Each item is answered with 1 of 3 markers: "usually" for 5 or more times a week, "sometimes" for 2-4 times a week, and "rarely" for never or 1 time a week. Higher scores reflect more disturbed sleep behavior.



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Participant (if possessing adequate understanding, in the investigator's opinion) and/or her parent(s)/legal representative is willing and able to give informed consent/assent for participation in the trial.
  • Participant and her 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 she has one) and consultant (if she has one) to be notified of participation in the trial, if the primary care practitioner/consultant is different to 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 her 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 travel outside the country of residence planned during the trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03848832


Locations
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United States, Alabama
Clinical Trial Site
Birmingham, Alabama, United States, 35294-0021
United States, California
Clinical Trial Site
San Diego, California, United States, 92123
United States, Colorado
Clinical Trial Site
Aurora, Colorado, United States, 80045
United States, Illinois
Clinical Trial Site
Chicago, Illinois, United States, 60612
United States, Maryland
Clinical Trial Site
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Clinical Trial Site
Boston, Massachusetts, United States, 02115
United States, Minnesota
Clinical Trial Site
Saint Paul, Minnesota, United States, 55101
United States, Missouri
Clinical Trial Site
Saint Louis, Missouri, United States, 63110-1093
United States, New York
Clinical Trial Site
Bronx, New York, United States, 10467
United States, Ohio
Clinical Trial Site
Cincinnati, Ohio, United States, 45229
United States, Pennsylvania
Clinical Trial Site
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Clinical Trial Site
Greenwood, South Carolina, United States, 29646
United States, Tennessee
Clinical Trial Site
Nashville, Tennessee, United States, 37232
United States, Texas
Clinical Trial Site
Houston, Texas, United States, 77030
Italy
Clinical Trial Site
Genoa, Italy, 16147
Clinical Trial Site
Messina, Italy, 98124
Clinical Trial Site
Milan, Italy, 20142
Clinical Trial Site
Rome, Italy, 00165
Spain
Clinical Trial Site
Barcelona, Spain, 08022
Clinical Trial Site
Barcelona, Spain, 08950
Clinical Trial Site
Madrid, Spain, 28009
Clinical Trial Site
Madrid, Spain, 28040
Clinical Trial Site
Valencia, Spain, 46026
United Kingdom
Clinical Trial Site
Liverpool, United Kingdom, L12 2AP
Clinical Trial Site
London, United Kingdom, SE1 7EU
Clinical Trial Site
London, United Kingdom, SE5 8BB
Sponsors and Collaborators
GW Research Ltd
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Responsible Party: GW Research Ltd
ClinicalTrials.gov Identifier: NCT03848832    
Other Study ID Numbers: GWND18064
2018-003370-27 ( EudraCT Number )
First Posted: February 21, 2019    Key Record Dates
Last Update Posted: November 17, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GW Research Ltd:
Cannabidiol
CBD
Epidiolex
GWP42003-P
Additional relevant MeSH terms:
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Rett Syndrome
Syndrome
Disease
Pathologic Processes
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Epidiolex
Anticonvulsants