RETT Syndrome With Proven MECP2 MutationPhase 2/3TRANSCENDNCT07257978
Efficacy and Safety of NTI164 in Children and Young Adults With Rett Syndrome
A Phase 2/3 study testing NTI164 in people with RETT Syndrome With Proven MECP2 Mutation and Rett Syndrome, run by Fenix Innovation Group at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 to 25 years, women only
- Conditions the study is for
- RETT Syndrome With Proven MECP2 Mutation, Rett Syndrome
- What is being tested?
- NTI164
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteAustralia
- Study dates
- 1 Jul 2027to 1 Oct 2028
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 25 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Michael C Fahey contact
Australia1 site
Monash Health
Clayton, Victoria, 3168
Kanan Sharma, +61395946666, MonashChildrensCTC@monashhealth.org
About this study
Official title: A Phase II/III Double-blind, Randomised, Placebo-controlled, Crossover Study Investigating the Efficacy and Safety of NTI164 in Children and Young Adults With Rett Syndrome
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.
Read the detailed description
The FENRTT2 study will investigate the efficacy and safety of a full-spectrum medicinal cannabis plant extract with extremely low THC, NTI164, on Rett syndrome (RTT). This study will be a randomised, placebo-controlled, double-blind, crossover study spanning from 28 weeks up t0 52 weeks.
RTT is a devastating rare genetic condition affecting females and involves debilitating physical and intellectual symptoms, with inflammation often driving the progression of symptoms. NTI164 is a potently anti-inflammatory oil which has demonstrated efficacy in reducing symptoms in several paediatric neurological conditions, including RTT (Phase I/II), autism spectrum disorder (ASD), and paediatric acute-onset neuropsychicatric syndrome (PANS). A Phase I/II clinical trial of NTI164 in RTT (FENRTT1) 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 will seek to demonstrate superiority over placebo in clinical outcomes in this cohort of patients. Multi-omic analyses on patient blood will also be included to further investigate the mechanism of action of NTI164, including transcriptomics, proteomics, phosphoproteomics, methylation, and cytokine analyses. Functional and clinical benefit will be measured using several validated, gold-standard assessment tools, rated by both clinicians and parents.
- Being tested
- NTI164, Placebo
- Keywords
- Rett syndrome, Rett, cannabis, NTI164
- Medical subject headings
- Rett Syndrome, Marijuana Abuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NTI164Drug
Also called FEN164
NTI164 is a full-spectrum medicinal cannabis plant extract with <0.3% THC.
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
| NTI164 active | Active comparator | NTI164 Receives: Drug: NTI164 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, Week 12, and Week 28
Secondary outcomes (7)
Clinical Global Impression - Severity (CGI-S)
7-point scale rating a clinician's impression of disease severity at a given time point, a higher score indicates more severe illness.
Measured: Baseline, Week 12, and Week 28
Clinical Global Impression - Improvement (CGI-I)
A clinician-rated tool to assess how much an individual's symptoms improve or worsen following an intervention on a 7-point scale. 1-3 = improvement, 4 = no change, 5-7 = worsening. It is anticipated the CGI-I score will be <4 following NTI164 treatment, indicating moderate-substantial improvement.
Measured: Baseline, Week 12, and Week 28
RTT-Domain- specific Concerns - Visual Analog Scale (RTT-DSC-VAS)
An 8-point scale assessing areas of functional impairment (0 = normal function, 7 = most severe impairment).
Measured: Baseline, Week 12, and Week 28
Impact of Childhood Neurologic Disability scale + Quality of Life (ICND + QoL)
Rates the effect of 4 health problems (inattentiveness, impulsivity, or mood; ability to think and remember; neurologic or physical limitations; epilepsy) on 11 aspects of the child and/or family's life (overall health, relationships with parents, relationships with siblings, relationship between your spouse/partner, relationships with child's friends/peers, social life - acceptability by others, social life - number of activities, school - academics, child's self-esteem, loss of original hopes for child/self, and family activities. A higher score indicates a lower level of disability. QoL component rates the QoL of the patient on a 6-point scale (1 = poor, 6 = excellent).
Measured: Baseline, Week 12, and Week 28
RTT-Caregiver Burden Inventory (RTT-CBI)
Assesses 4 aspects of burden (physical, emotional, and social burden, and time dependence) on the primary caregiver of the patient. Subdomains include general caregiver tasks, emotional and social impact of caregiving, and financial burden. A higher score indicates greater impairment and caregiver burden.
Measured: Baseline, Week 12, and Week 28
EQ-5D-Y-5L
A descriptive scale covering 5 dimensions of health (mobility, looking after myself, doing usual activities, having pain or discomfort, and feeling worried, sad, or unhappy). This version of the scale has 5 levels to each answer (5L) and is worded so as to be more child friendly (Y). A higher score indicates greater impairment/worse health status.
Measured: Baseline, Week 12, and Week 28
CSBS-DP-IT
A caregiver rated scale often used as the first step in routine screening to determine if a developmental evaluation is needed. In the context of RTT, it can be used to assess functional communication. A higher score indicates a better communication ability.
Measured: Baseline, Week 12, and Week 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2025
- Study start1 Jul 2027 (estimated)
- Primary completion1 Oct 2028 (estimated)
- Study completion1 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RETT Syndrome With Proven MECP2 MutationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Randomised, placebo-controlled, double-blind, crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fenix Innovation Group
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Neurotech International Limited
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07257978
- Sponsor's protocol ID
- NTIRTT2
- Other IDs
- NTIRTT2
- Acronym
- TRANSCEND
- Status last verified
- Sep 2026
- First submitted
- 18 Jul 2025
- Last updated
- 9 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II/III Double-blind, Randomised, Placebo-controlled, Crossover Study Investigating the Efficacy and Safety of NTI164 in Children and Young Adults With Rett Syndrome
- ClinicalTrials.gov ID
- NCT07257978
- Acronym / sponsor ID
- TRANSCEND / NTIRTT2
- Keywords
- Rett syndrome, Rett, cannabis, NTI164
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Fenix Innovation GroupIndustry (pharma, biotech, devices)
- Collaborators
- Neurotech International Limited
- Study start
- 1 Jul 2027 (estimated)
- Primary completion
- 1 Oct 2028 (estimated)
- Study completion
- 1 Oct 2028 (estimated)
- First posted
- 2 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The FENRTT2 study will investigate the efficacy and safety of a full-spectrum medicinal cannabis plant extract with extremely low THC, NTI164, on Rett syndrome (RTT). This study will be a randomised, placebo-controlled, double-blind, crossover study spanning from 28 weeks up t0 52 weeks.
RTT is a devastating rare genetic condition affecting females and involves debilitating physical and intellectual symptoms, with inflammation often driving the progression of symptoms. NTI164 is a potently anti-inflammatory oil which has demonstrated efficacy in reducing symptoms in several paediatric neurological conditions, including RTT (Phase I/II), autism spectrum disorder (ASD), and paediatric acute-onset neuropsychicatric syndrome (PANS). A Phase I/II clinical trial of NTI164 in RTT (FENRTT1) 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 will seek to demonstrate superiority over placebo in clinical outcomes in this cohort of patients. Multi-omic analyses on patient blood will also be included to further investigate the mechanism of action of NTI164, including transcriptomics, proteomics, phosphoproteomics, methylation, and cytokine analyses. Functional and clinical benefit will be measured using several validated, gold-standard assessment tools, rated by both clinicians and parents.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomised, placebo-controlled, double-blind, crossover
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
| NTI164 active | Active comparator | Drug: NTI164NTI164 |
Who may qualify
- Ages
- 4 to 25 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (10 listed)
- 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®
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NTI164Also: FEN164NTI164 is a full-spectrum medicinal cannabis plant extract with <0.3% THC. | Drug | NTI164 active |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Rett Syndrome Behaviour Questionnaire (RSBQ)
Time frame: Baseline, Week 12, and Week 28
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.
7 secondary outcomes
Clinical Global Impression - Severity (CGI-S)
Time frame: Baseline, Week 12, and Week 28
Clinical Global Impression - Improvement (CGI-I)
Time frame: Baseline, Week 12, and Week 28
RTT-Domain- specific Concerns - Visual Analog Scale (RTT-DSC-VAS)
Time frame: Baseline, Week 12, and Week 28
Impact of Childhood Neurologic Disability scale + Quality of Life (ICND + QoL)
Time frame: Baseline, Week 12, and Week 28
RTT-Caregiver Burden Inventory (RTT-CBI)
Time frame: Baseline, Week 12, and Week 28
EQ-5D-Y-5L
Time frame: Baseline, Week 12, and Week 28
CSBS-DP-IT
Time frame: Baseline, Week 12, and Week 28
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michael C Fahey contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing NTI164 in people with RETT Syndrome With Proven MECP2 Mutation and Rett Syndrome, run by Fenix Innovation Group at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kanan Sharma (+61395946666, MonashChildrensCTC@monashhealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rett Syndrome Behaviour Questionnaire (RSBQ) (time frame: Baseline, Week 12, and Week 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2026.