Clinical trial NCT03802799: Open Label Extension to Assess the Long-Term Safety and Tolerability of ZYN002 in Children and Adolescents With FXS
Official title: An Open-Label Extension Study to Assess the Long-Term Safety and Tolerability of ZYN002 Administered as a Transdermal Gel to Children, Adolescents, and Young Adults With Fragile X Syndrome
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
PHASE3
Conditions: Fragile X Syndrome
Lead sponsor: Zynerba Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2019-01-14
Enrollment: 550
Sex: ALL
Minimum age (years): 3
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-Label
Primary purpose: TREATMENT

Brief summary: ZYN002 is a pharmaceutically manufactured Cannabidiol that is developed as a clear gel that can be applied to the skin (called transdermal delivery).

The gel will be applied to clean, dry, intact skin of the shoulders and/or upper arms.

Participants from the ZYN2-CL-016 and ZYN2-CL-033 studies who meet the inclusion criteria and none of the exclusion criteria for study ZYN2-CL-017 are eligible.

Parents/caregivers will apply the study gel twice daily for the 52-week treatment period.

Detailed description: This is an open-label extension, multiple-center study, to assess the long-term safety and tolerability of cannabidiol administered as ZYN002, a transdermal gel, for the treatment of child and adolescent patients with Fragile X Syndrome (FXS). Male and female patients with FXS will be treated for up to 72 months. Up to 450 male and female patients, ages 3 to 18 years will be enrolled.

Parents/caregivers will apply the study gel twice daily for the 52-week treatment period.

Participants from study ZYN-CL-016 who weigh less than or equal to 35 kg, will receive 1 sachet of ZYN002, applied every 12 hours (± 2 hours).

Participants from study ZYN-CL-016 who weigh more than 35 kg will receive 2 sachets of ZYN002, applied every 12 hours (± 2 hours).

Participants from study ZYN-CL-033 who weigh less than or equal to 30 kg, will receive 1 sachet of ZYN002, applied every 12 hours (± 2 hours).

Participants from study ZYN-CL-033 who weigh more than 30 kg will receive 2 sachets of ZYN002, applied every 12 hours (± 2 hours).

Participants from study ZYN-CL-033 who weigh more than 50 kg will receive 3 sachets of ZYN002, applied every 12 hours (± 2 hours).

At the Investigator's discretion, the dose may be increased or decreased at any time after the first month of treatment (for example due to weight changes during the course of the study).

Participants who are taking anti-epileptic drugs may have an additional one or two weeks of treatment after the 52 week treatment period to taper off study treatment.

Blood samples will be collected for safety analysis of ZYN002. Additionally, the parents/caregivers will be asked to complete some questionnaires. There will be other questionnaires and scales that will be completed at the site by the study doctor and/or with the participant and their parents/caregivers.

Patients that complete Month 12 will be allowed to continue for another 12 months of treatment if they qualify. Patients will be evaluated again annually at Months 24 and 36, and 48 in order to remain in the study.

Eligibility criteria: Inclusion Criteria:

* Participated in study ZYN2-CL-016 or Study ZYN2-CL-033.
* Patients and parents/caregivers agree to abide by all study restrictions and comply with all study procedures.
* Patients and parents/caregivers must be adequately informed of the nature, risks of the study, and give written informed consent prior to enrollment in ZYN2-CL-017.
* In the Investigator's opinion, the patients and parents/caregivers are reliable and are willing and able to comply with all protocol requirements and procedures.
* Females of childbearing potential must have a negative pregnancy test at all designated visits

Exclusion Criteria:

* Patient is receiving any investigational drugs (not ZYN002) or using any experimental devices.
* Patient has an ongoing serious adverse event (SAE) or has experienced a SAE in ZYN2-CL-016 or ZYN2-CL-033, which in the opinion of the Investigator, should exclude them from participation.
* Females who are pregnant, nursing, or planning a pregnancy; females of childbearing potential and male patients with a partner of childbearing potential who are unwilling or unable to use an acceptable method of contraception for the duration of therapy and for three months after the last dose of trial drug.
* Patients who have alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels ≥ 2 times the upper limit of normal (ULN) or has alkaline phosphatase levels ≥ 3 times the ULN as determined from patient safety laboratories.

Primary outcomes:
measure: To evaluate the long-term safety and tolerability of ZYN002 administered as a transdermal gel formulation.
timeFrame: Up to 96 month.
Secondary outcomes:
measure: To evaluate the long-term efficacy of ZYN002 in the treatment of symptoms of FXS.
timeFrame: Change from baseline to end of treatment
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Southwest Autism Research and Resource Center
state: Arizona
city: Culver City
country: United States
facility: Science 37
state: California
city: Irvine
country: United States
facility: Amnova Clinical Research, LLC
state: California
city: Sacramento
country: United States
facility: UC Davis Health System, MIND Institute
state: California
city: Denver
country: United States
facility: Children's Hospital of Colorado
state: Colorado
city: Washington
country: United States
facility: Children's Research Institute
state: District of Columbia
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Han Phan
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Kennedy Krieger Institute
state: Maryland
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Masonic Institute of Developing Brain
state: Minnesota
city: Jackson
country: United States
facility: University of Mississipi Medical Center
state: Mississippi
city: New York
country: United States
facility: The Fragile X Spectrum Disorder Clinic at Icahn School of Medicine at Mount Sinai, Division of Medical Genetics
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Tulsa
country: United States
facility: Central States Research
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Greenville
country: United States
facility: Greenwood Genetic Center
state: South Carolina
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Sydney
country: Australia
facility: Westmead Children's Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Lady Cilento Children's Hospital - South Brisbane
state: Queensland
city: Melbourne
country: Australia
facility: Genetics Clinics Australia
state: Victoria
city: Wellington
country: New Zealand
facility: Wellington Hospital
city: Leicester
country: United Kingdom
facility: Research Space
state: Leicestershire
city: Edinburgh
country: United Kingdom
facility: Children's Clinical Research Facility, Royal Hospital for Children and Young People
state: Lothian
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
Study officials:
References:
citation: Heussler HS. Emerging Therapies and challenges for individuals with Angelman syndrome. Curr Opin Psychiatry. 2021 Mar 1;34(2):123-128. doi: 10.1097/YCO.0000000000000674.