Assessing the Safety and Efficacy of Full-Spectrum Medicinal Cannabis Plant Extract 0.08% THC (NTI164) in the Treatment of Rett Syndrome (RTT)

Assessing the Safety and Efficacy of Full-Spectrum Medicinal Cannabis Plant Extract 0.08% THC (NTI164) in the Treatment of Rett Syndrome (RTT)

This 18-week open-label study examines the effectiveness of Full-Spectrum Medicinal Cannabis Plant Extract containing 0.08% THC (NTI164) in treating Rett syndrome (RTT) in children and young people. The study aims to determine the impact of NTI164 on RTT symptoms over a 16-week treatment period.

Participants will start with a daily dose of 5 mg/kg of NTI164, which will be gradually increased over four weeks until they reach either the maximum tolerated dose or 20 mg/kg per day. They will then maintain this dose for eight weeks. Following this treatment phase, the dosage will be reduced by 5 mg/kg each week for four weeks until treatment concludes.

The effectiveness of the treatment will be assessed using tailored questionnaires that measure changes in the patients' conditions. Additionally, full blood examinations will be conducted at multiple points throughout the study to monitor the effects of the treatment.

This study is an 18-week open-label trial designed to assess the effectiveness of Full-Spectrum Medicinal Cannabis Plant Extract containing 0.08% THC (NTI164) on the severity of symptoms in children and young people with Rett syndrome (RTT). The main objective is to determine how well NTI164 alleviates the symptoms of RTT over a 16-week treatment period.

The study involves multiple phases:

1. **Up-titration Phase (4 weeks):** Treatment begins with an initial daily dose of 5 mg/kg of NTI164. Over the first four weeks, this dose is incrementally increased based on patient tolerance, aiming for a maximum daily dose of 20 mg/kg.
2. **Treatment Phase (8 weeks):** Once the maximum tolerated dose is established, participants continue to receive this dose for the following eight weeks. This phase focuses on maintaining a steady dosage to observe the therapeutic effects on RTT symptoms.
3. **Down-titration Phase (4 weeks):** After completing the treatment phase, the dosage is systematically reduced by 5 mg/kg each week for four weeks until treatment cessation. This gradual reduction helps in assessing any withdrawal effects and the stability of symptom improvement post-treatment.

Throughout the study, the efficacy of NTI164 is evaluated using specifically designed questionnaires that track changes in the emotional, behavioral, and cognitive functions of the participants, providing insights into how the treatment impacts various aspects of RTT. Additionally, full blood examinations are conducted at key points during the study to monitor the physiological responses to the treatment and to ensure the safety and tolerability of NTI164. This comprehensive approach allows for a detailed assessment of both the immediate and longer-term effects of the medicinal cannabis extract on Rett syndrome symptoms.

Inclusion Criteria:

• Girls and women, aged 5-20 years
• Weight greater than or equal to 12kg
• Classical/typical RTT
• Documented disease-causing mutation in MECP2 gene
• At least 6 months post regression at screening (ie. no loss or degradation in ambulation, hand function, speech, nonverbal communicative or social skills within 6 months of screening) Rett Syndrome Clinical Severity Scale rating of 10-36
• CGI score of 4 or higher.
• Stable pattern of seizures, or has had no seizures, within 8 weeks of screening.

Exclusion Criteria:

• Current clinically significant cardiovascular, endocrine (such as hypo- or hyperthyroidism, type 1 diabetes, or uncontrolled type 2 diabetes), renal, hepatic, respiratory, or gastrointestinal disease (such as celiac disease or inflammatory bowel disease), or major surgery planned during the study.
• Known history or symptoms of long QT syndrome.
• QTcF interval >450 ms, history of risk factor for torsades de pointes or clinically significant QT prolongation deemed to increase risk.
• Treatment with insulin, IGF-1, or growth hormone within 12 weeks of baseline.
• Currently receiving treatment with DAYBUETM (trofinetide).
• Currently using other unregistered drugs for the treatment of Rett syndrome such as Anavex.
• Currently using or has used recreational or medicinal cannabis, cannabinoid-based medications (including Sativex®, or Epidiolex®) within the 12 weeks prior to screening and is unwilling to abstain for the duration of the trial.
• Participant has any known or suspected hypersensitivity to cannabinoids or any of the excipients.