CompletedPhase 2ACTRN12618001063202

Clinical study Of caNNabidiol in childrEn and adolesCenTs with Fragile X (CONNECT-FX)

A Randomized, Double-Blind, Placebo-Controlled Multiple-Center, Efficacy and Safety Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents with Fragile X Syndrome – CONNECT-FX

Sponsor

Zynerba Pharmaceuticals Pty. Ltd.

Enrollment

204 participants

Start Date

Jun 28, 2018

Study Type

Interventional

Conditions

Fragile X Syndrome

Summary

This study is evaluating the efficacy and safety of ZYN002, a clear gel that can be applied to the skin (called transdermal application) twice a day for treatment of symptoms of Fragile X Syndrome (FXS) Who is it for? Patients who have been diagnosed with Fragile X Syndrome and are aged between 3 and less than 18 years old. Study details All participants will undergo a screening process. Eligible participants will be randomized 1:1 to drug and placebo and will undergo up to a 14-week treatment period. Participants who are taking anti-epileptic drugs may undergo an additional 1-2 weeks of blinded treatment to taper off study drug treatment. During the treatment period, all participants may be either assigned to ZYN002 or placebo. All participants may receive placebo during the trial. The assignment will be done by a computer generated system and neither the study doctor or the participant or their caregivers will know which treatment is being given to them. The dose of the treatment will depend on the weight of the participants. If the participants weigh less than or equal to 35kg, they will receive 2 sachets of the gel through the day (1 sachet approximately every 12 hours) and if they weigh more than 35kg, they will receive 4 sachets of gel per day (2 sachets approximately every 12 hours). Parents/ caregivers will be instructed on proper application of the gel. The gel will be applied to clean, dry, intact skin of the upper arms/ shoulders. Blood samples will be collected for safety analysis of ZYN002. An independent analytical laboratory will also perform CGG repeat and methylation status analyses. 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. Participation in this study may help the child’s/ adolescent’s FXS symptoms; however, we cannot guarantee that he/ she will get any benefits from this study. The results of this study may benefit future patients.

Eligibility

Sex: Both males and femalesMin Age: 3 YearssMax Age: 17 Yearss

Inclusion Criteria12

Male or female children and adolescents aged 3 to less than 18 years, at the time of Screening.
Judged by the Investigator to be in generally good health at Screening based upon the results of a medical history, physical examination, 12-lead ECG, and clinical laboratory test results. Laboratory results outside of the reference range must be documented as not clinically significant by both the Investigator and Sponsor.
Patients must have a diagnosis of FXS through molecular documentation of FMR1 full mutation.
Patients must be assessed by the Investigator as being moderately to severely impacted due to FXS.
Patients with a history of seizure disorders must currently be receiving treatment with a stable regimen of one or two AEDs, or must be seizure-free for one year if not currently receiving AEDs.
Patients who are taking psychotropic medication(s) should be on a stable regimen of no more than two such medications for at least four weeks preceding study Screening and must maintain that regimen throughout the study.
If patients are receiving non-pharmacological, behavioral, and/or dietary interventions, they must be stable and have been doing so for three months prior to Screening.
Patients have a body mass index between 12–30 kg /m2 (inclusive).
Females of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative serum or urine pregnancy test at all designated visits.
Patients and parents/caregivers must be adequately informed of the nature and risks of the study and give written informed consent (and assent if applicable) prior to Screening.
Parents/caregiver(s) must provide written consent to assist in trial drug administration.
In the Investigator’s opinion, patients and parents/caregivers are reliable and willing and able to comply with all protocol requirements and procedures.

Exclusion Criteria20

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 study medication.
History of significant allergic condition, significant drug-related hypersensitivity, or allergic reaction to any compound or chemical class related to ZYN002 or its excipients.
Exposure to any investigational drug or device <=30 days prior to Screening or at any time during the study.
Patient has alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin levels greater than or equal to 2 times the upper limit of normal (ULN) or has alkaline phosphatase levels greater than or equal to 3 times the ULN as determined from Screening safety laboratories.
Use of cannabis or any THC or CBD-containing product (aside from ZYN002) within three months of Screening Visit or during the study.
Patient has a positive drug screen, including ethanol, cocaine, THC, barbiturates, amphetamines (unless prescribed), benzodiazepines, and opiates.
Patient is using the following AEDs: clobazam, phenobarbital, ethosuximide, felbamate, or vigabatrin.
Patient is using any strong inhibitor/inducer of CYP3A4 or sensitive substrate for CYP3A4
Patients may not be taking minocycline for 30 days prior to Screening or throughout the study.
Patients may not be taking any benzodiazepines at screening or throughout the study.
Patient has an advanced, severe, or unstable disease that may interfere with the study outcome evaluations.
Patient is expected to initiate or change pharmacologic or non-pharmacologic interventions during the course of the study.
Patient has an acute or progressive neurological disease, psychosis, schizophrenia, or any psychiatric disorder or severe mental abnormalities (other than Fragile X Syndrome) that are likely to require changes in drug therapy or interfere with the objectives of the study or the ability to adhere to protocol requirements.
Patient has a positive result for the presence of Hepatitis B Surface antigen (HBsAg), Hepatitis C virus antibodies (HCV), or human immunodeficiency virus (HIV) antibodies.
Has suspected or confirmed cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, cardiac conduction problems, exercise-related cardiac events including syncope and pre-syncope, risk factors for Torsades de pointes (e.g. heart failure, hypokalemia, family history of Long QT Syndrome), or other serious cardiac problems .
Any clinically significant condition or abnormal findings at the Screening Visit that would, in the opinion of the Investigator, preclude study participation or interfere with the evaluation of the study medication.
Any skin disease or condition, including eczema, psoriasis, melanoma, acne, contact dermatitis, scarring, imperfections, lesions, tattoos, or discoloration, that may affect treatment application, application site assessments, or absorption of the trial drug.
History of treatment for, or evidence of, drug abuse within the past year.
Previous participation in a ZYN002 study.
Patient responds “yes” to Question 4 or 5 on the C-SSRS (Children) during Screening or at any time on study

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Interventions

ZYN002 is a pharmaceutically manufactured Cannabidiol (CBD) 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, in

ZYN002 is a pharmaceutically manufactured Cannabidiol (CBD) 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. All participants will undergo a screening process. Eligible participants will then participate in up to a 14 week treatment period, where all participants may receive placebo or active study drug Treatment group A (ZYN002): Parents/caregivers will apply the study gel twice daily for the treatment period. Participants who weigh less than or equal to 35 kg, will receive 1 sachet of ZYN002, applied every 12 hours (± 2 hours). • Participants who weigh more than 35 kg will receive 2 sachets of ZYN002, applied every 12 hours (± 2 hours). Participants who are taking Anti-epileptic drugs may have an additional one or two weeks of blinded treatment to taper off study treatment. After the final dose, patients will be followed weekly for 4 weeks by telephone, prior to discharge from the study. Patient compliance with the intervention will be monitored by the study coordinator through drug accountability at each study visit.