Efficacy and Safety of NTI164 in Children and Young Adults With Rett Syndrome

NCT07257978 | Not Yet Recruiting Phase 2

• 1 other identifier: NTIRTT2
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The FENRTT2 study will investigate the efficacy and safety of a medicinal cannabis plant extract with extremely low THC (delta-9-tetrahydrocannabinol), NTI164, on Rett syndrome (RTT) in a crossover design. RTT is a devastating rare genetic condition affecting females and involves debilitating physical and intellectual symptoms. NTI164 is an oil which has demonstrated efficacy in reducing symptoms in several paediatric neurological conditions, including RTT, autism spectrum disorder (ASD), and paediatric acute-onset neuropsychicatric syndrome (PANS). A Phase I/II clinical trial of NTI164 in RTT (FENRTT1/NTIRTT1) showed NTI164 is safe in this population and significantly improved overall clinical severity of illness, as well as core RTT symptoms, including anxiety, mental alertness, communication skills, socialisation/eye contact, and attentiveness. The FENRTT2 study will investigate NTI164 in a larger number of patients, and compare NTI164 to a placebo control. Research tests on patient blood will also be included to further investigate how NTI164 works in the body.

Conditions

RETT Syndrome With Proven MECP2 Mutation; Rett Syndrome

Keywords

Rett syndrome; Rett; cannabis; NTI164

Outcome Measures

Primary Outcomes (1)

• Rett Syndrome Behaviour Questionnaire (RSBQ)

  A validated, FDA-accepted 45-item caregiver-assessed tool to assess a variety of behavioural features impaired in RTT. The caregiver rates items as 0 = not true, 1 = somewhat true or sometimes true, or 2 = very true. Symptoms assessed include maladaptive behaviours, mood disruption, repetitive movements, fear/anxiety, breathing abnormalities, hand behaviours, and gross motor skills. A higher score indicates greater impairment/disease severity.

  Baseline, Week 12, and Week 28

Secondary Outcomes (7)

• Clinical Global Impression - Severity (CGI-S)

  Baseline, Week 12, and Week 28

• Clinical Global Impression - Improvement (CGI-I)

  Baseline, Week 12, and Week 28

• RTT-Domain- specific Concerns - Visual Analog Scale (RTT-DSC-VAS)

  Baseline, Week 12, and Week 28

• Impact of Childhood Neurologic Disability scale + Quality of Life (ICND + QoL)

  Baseline, Week 12, and Week 28

• RTT-Caregiver Burden Inventory (RTT-CBI)

  Baseline, Week 12, and Week 28

Other Outcomes (4)

• Research bloods - transcriptomics

  Baseline, Week 12, Week 16, and Week 28

• Research bloods - proteomics (and phosphoproteomics)

  Baseline, Week 12, Week 16, Week 28

• Research bloods - methylomics

  Baseline, Week 12, Week 16, Week 28

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

NTI164 active

ACTIVE COMPARATOR

NTI164

Drug: NTI164

Interventions

NTI164 DRUG

NTI164 is a full-spectrum medicinal cannabis plant extract with \<0.3% THC.

Also known as: FEN164

NTI164 active

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 4 Years - 25 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Females aged 4-25 years of age
• Weight ≥12 kg
• Classical/typical RTT as confirmed with a documented pathogenic variant in the MECP2 gene
• At least 6 months post-regression at screening (i.e. no loss or degradation in ambulation, hand function, speech, non-verbal communication, or social skills within 6 months of screening)
• Rett Syndrome Clinical Severity Scale rating of 10-36
• Clinical Global Impression - Severity of Illness score ≥4
• Stable pattern of seizures or has had no seizures within 8 weeks of screening, as determined by the participant's primary physician
• Other patient medications must be stable (i.e. no dose adjustments) for at least 8 weeks prior to screening, including steroids, anti-inflammatories, anxiolytics etc

You may not qualify if:

• 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 coeliac disease or inflammatory bowel disease), or major surgery planned
• Known history or symptoms of long QT syndrome
• QTcF interval \>450 milliseconds, history of risk factor for torsades de pointes or clinically significant QT prolongation deemed to increase risk
• Currently receiving treatment with DAYBUE™ (Trofinetide)
• Currently using other unregistered drugs for the treatment of Rett syndrome, such as Anavex®
• Currently using or has used recreational or medicinal cannabis or 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
• A known or suspected hypersensitivity to cannabinoids or any of the excipients
• Moderate-severe impairment in hepatic function at screening, defined as serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2 x upper limit of normal (ULN), or total bilirubin (TBL) \> 2 x ULN. This criterion can only be confirmed once laboratory results are available, participants enrolled into the trial who are later found to meet this criterion will be screen-failed.
• Participant is enrolled in another clinical trial within 14 days of screening or becomes enrolled in another clinical trial throughout the duration of this study
• Infection and/or antibiotic use in the 2 weeks prior to screening (participants can be recruited following 2 weeks without infection and/or antibiotic use)

Sponsors & Collaborators

• Fenix Innovation Group: lead
• Neurotech International Limited: collaborator

Study Sites (1)

Monash Health

Clayton, Victoria, 3168, Australia

Location

MeSH Terms

Conditions

Rett Syndrome; Marijuana Abuse

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Central Study Contacts

Kanan Sharma

CONTACT

+61395946666; MonashChildrensCTC@monashhealth.org

Michael C Fahey

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All parties other than the Clinical Trials Pharmacy and Sponsor will be blinded during the Active study phase (up to Week 28).
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomised, placebo-controlled, double-blind, crossover

Study Record Dates

• First Submitted: July 18, 2025
• First Posted: December 2, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: December 2, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)