Rett Syndrome, RETT Syndrome With Proven MECP2 Mutation
Conditions
Keywords
Rett syndrome, Rett, cannabis, NTI164
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.
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.
Interventions
DRUGNTI164
NTI164 is a full-spectrum medicinal cannabis plant extract with \<0.3% THC.
DRUGPlacebo
Placebo
Sponsors
Fenix Innovation Group
Neurotech International Limited
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All parties other than the Clinical Trials Pharmacy and Sponsor will be blinded during the Active study phase (up to Week 28).
Intervention model description
Randomised, placebo-controlled, double-blind, crossover
Eligibility
Sex/Gender
FEMALE
Age
4 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
1. Females aged 4-25 years of age 2. Weight ≥12 kg 3. Classical/typical RTT as confirmed with a documented pathogenic variant in the MECP2 gene 4. 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) 5. Rett Syndrome Clinical Severity Scale rating of 10-36 6. Clinical Global Impression - Severity of Illness score ≥4 7. Stable pattern of seizures or has had no seizures within 8 weeks of screening, as determined by the participant's primary physician 8. 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
Exclusion criteria
1. 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 2. Known history or symptoms of long QT syndrome 3. QTcF interval \>450 milliseconds, history of risk factor for torsades de pointes or clinically significant QT prolongation deemed to increase risk 4. Currently receiving treatment with DAYBUE™ (Trofinetide) 5. Currently using other unregistered drugs for the treatment of Rett syndrome, such as Anavex® 6. 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 7. A known or suspected hypersensitivity to cannabinoids or any of the excipients 8. 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. 9. 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 10. 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rett Syndrome Behaviour Questionnaire (RSBQ) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression - Severity (CGI-S) | Baseline, Week 12, and Week 28 | 7-point scale rating a clinician's impression of disease severity at a given time point, a higher score indicates more severe illness. |
| Clinical Global Impression - Improvement (CGI-I) | Baseline, Week 12, and Week 28 | 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. |
| RTT-Domain- specific Concerns - Visual Analog Scale (RTT-DSC-VAS) | Baseline, Week 12, and Week 28 | An 8-point scale assessing areas of functional impairment (0 = normal function, 7 = most severe impairment). |
| Impact of Childhood Neurologic Disability scale + Quality of Life (ICND + QoL) | Baseline, Week 12, and Week 28 | 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). |
| RTT-Caregiver Burden Inventory (RTT-CBI) | Baseline, Week 12, and Week 28 | 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. |
| CSBS-DP-IT | Baseline, Week 12, and Week 28 | 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. |
| EQ-5D-Y-5L | Baseline, Week 12, and Week 28 | 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. |
Countries
Australia
Contacts
CONTACTKanan Sharma
CONTACTMichael C Fahey
Outcome results
None listed