XanaCIDD: A clinical study in which participants are randomly assigned to take either active drug or placebo (non active) to assess if the drug Xanamem is safe, tolerable and effective in helping adult patients with cognitive impairment due to depressive disorder
| ISRCTN | ISRCTN52254972 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN52254972 |
| EudraCT/CTIS number | 2023-000030-15 |
| IRAS number | 1007376 |
| ClinicalTrials.gov number | NCT05657691 |
| Secondary identifying numbers | ACW0008, IRAS 1007376, CPMS 56832 |
- Submission date
- 04/03/2023
- Registration date
- 24/08/2023
- Last edited
- 30/05/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Mental and Behavioural Disorders
Plain English summary of protocol
Background and study aims
This study will test the safety and tolerability (how well the body tolerates) of Xanamem in adults with clinical depression, with ongoing symptoms of low mood and some difficulty with thinking or memory. The study will also test the effectiveness (how well it works) of Xanamem on symptoms that happen with depression, such as sadness and loss of pleasure, tiredness, loss of energy, and difficulty concentrating and thinking.
Who can participate?
The study will take place at up to 4 sites in the UK, as well as 11 sites in Australia. Approximately 160 participants aged 18 – 70 years with major depressive disorder will take part in the study.
What does the study involve?
Participants will be assigned by chance to 1 of 2 treatment groups of equal size - Xanamem or placebo. Neither the participants, the study doctor, or the sponsor of the study will know which group participants are in (called a randomised, double-blind study). Participants will take part in the trial for up to 14 weeks. This includes a screening period of up to 4 weeks, a treatment period of 6 weeks, and a follow-up period of 4 weeks. Participants will have several safety tests done at visits to the study site, such as checking blood pressure and heart rate, physical examination, and blood tests. They will also take several questionnaires and tests to measure their thinking and memory.
What are the possible benefits and risks of participating?
Benefits:
Not provided at time of registration
Risks:
Potential risks of participation for subjects are identified as:
Very common (10% of people tested or more, or at least 10 in 100)
• Headache
Common (between 1% and 10% of people tested, or 1 in 100 to 10 in 100)
• Nausea (feeling unwell)
• Diarrhoea
• Fatigue (tiredness)
• Dizziness
• Tingling in hands or feet
• Joint stiffness
• Back pain
• Blood test indicating mild irritation to the liver (raised ALT)
• Reduced number of nerve fibres in a skin biopsy sample, analysed under a microscope.
Because the investigational product (Xanamem) is at an early stage of development, there may be as yet unknown side effects. However, Xanamem has been previously given to people as single and multiple daily doses up to 70 mg (7 times higher than the doses in this research project) in earlier studies and has been given to over 300 people, including healthy people and people with mild dementia due to Alzheimer’s disease. There were no serious, severe, or life-threatening events due to Xanamem treatment. The majority of AEs reported to date were mild or moderate in severity. All AEs will be monitored to resolution and subjects will be encouraged to contact the site if any unexpected events occur between study visits.
In addition to their routine care, subjects choosing to participate in the study will be required to attend the required visits at the study centre. Efforts will be made to schedule the visits to minimise any inconvenience to subjects.
As part of their participation, subjects also will be required to complete the required questionnaires and other diagnostic instruments. Subjects will be able to take reasonable rest breaks, or assessments may be rescheduled to another day, if they become fatigued during the assessments. Subjects are also required to undergo additional study specific procedures as described in the protocol and made known to subjects in the informed consent document. This includes the risk of skin irritation from the ECG patches and bruising, swelling or bleeding from blood collection, for which a topical local anaesthetic cream will be offered if required.
Where is the study run from?
Axiom Real-Time Metrics (UK)
When is the study starting and how long is it expected to run for?
February 2023 to August 2024
Who is funding the study?
Actinogen (Australia)
Who is the main contact?
Dr Stuart Ratcliffe, stuartratcliffe@stpancrasclinical.com
Contact information
Scientific
Suite 901, Level 9
109 Pitt Street
Sydney
NSW 2000
Australia
| Phone | +61 2 8964 7401 |
|---|---|
| dana.hilt@actinogen.com.au |
Principal Investigator
3 White Lyon Court
Barbican
London
EC2Y 8EA
United Kingdom
| Phone | +44 203 865 1142 |
|---|---|
| stuartratcliffe@stpancrasclinical.com |
Public
Suite 901, Level 9
109 Pitt Street
Sydney
NSW 2000
Australia
| Phone | +61 2 8964 7401 |
|---|---|
| harinder.chera@actinogen.com.au |
Study information
| Study design | Interventional double-blind randomized parallel-group placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a participant information sheet |
| Scientific title | XanaCIDD: A double-blind, randomized, placebo-controlled, parallel-group trial to assess the safety, tolerability, and efficacy of Xanamem® in adults with cognitive impairment due to depressive disorder |
| Study acronym | XanaCIDD |
| Study objectives | Primary objective: To determine the effects of Xanamem on attention, including working memory. Secondary objective: To determine the effects of Xanamem on depressive symptoms. To determine the effects of Xanamem on executive function. To determine the effects of Xanamem on episodic memory. |
| Ethics approval(s) |
Approved 21/08/2023, Wales REC 1 (Health and Care Research Wales Support and Delivery Centre, Castlebridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, United Kingdom; +44 1792 606334; Wales.REC1@wales.nhs.uk), ref: 23/WA/0069 |
| Health condition(s) or problem(s) studied | Cognitive impairment due to depressive disorder |
| Intervention | ACW0008 is Phase 2, randomized, placebo-controlled, parallel-group, double-blind, proof-of-concept trial involving subjects with a confirmed diagnosis of MDD and who continue to experience cognitive impairment and depressive symptoms Subjects are assigned at 1:1 ratio to receive either a single dose of 10mg Xanamem or Placebo orally each day. Subjects will take part in the trial for up to 14 weeks. The trial consists of a Screening period (maximum 4 weeks), treatment period (6 weeks), and follow-up period (4 weeks). During the treatment period, participants and all personnel involved with the conduct and interpretation of the trial will be blinded to treatment codes. To conceal the blind, Investigational product and Placebo are identical in appearance and dispensing of trial drug will be coordinated by a Randomization and Trial Supply Management system (RTSM). The system will assign a bottle number corresponding to the randomization arm. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Xanamem |
| Primary outcome measure | Attention and working memory is measured using digital tests from a cognitive test battery (CTB) (Detection, Identification, and One Back tests) at Screening, Baseline, Week 2, Week 4, Week6, Week10 |
| Secondary outcome measures | Measured at Screening, Baseline, Week 2, Week 4, Week 6, Week10, unless otherwise noted: 1. Depression measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) 2. Executive Function is measured using a digital and paper and pencil cognitive tests (One Back Test, Category Fluency Test [CFT], Letter Fluency Test [LFT], and International Digit Symbol Substitution Test - Symbols [IDSST-S]) 3. Episodic Memory is measured using a digital and paper and pencil cognitive tests (One Card Learning and Hopkins Verbal Learning Test – Revised [HVLT-R], Immediate Recall only) 4. Individual tests of the CTB including Cogstate tests and other cognitive tests (HVLT-R, CFT, and LFT) 5. The responder rate will be measured by the percentage of participants achieving a 50% or greater reduction in MADRS score and Percentage of participants achieving a MADRS score of < 10 points at Week 6 (EOT) 6. Durability of cognitive and anti-depressive Xanamem effects will be measured by comparing scores 4 weeks after receiving last dose of trial drug (Week 6 vs Week 10) 7. Subjective clinical significance will be measured by the Patient’s Global Impression of Severity scale (PGI-S) 8. Subjective clinical improvement will be measured by the Patient’s Global Impression of Improvement scale (PGI-I) at week 6 9. Safety and tolerability will be measured by: 9.1. Incidence and severity of treatment emergent adverse events (TEAEs) 9.2. Incidence of SAEs and suspected unexpected serious adverse reactions (SUSARs) 9.3. Clinically significant changes from Baseline in: 9.3.1. Clinical safety laboratory evaluations 9.3.2. Vital signs 9.3.3. Physical examinations 9.3.4. Columbia-Suicide Severity Rating Scale (C-SSRS) 10. Sparse pharmacokinetic sampling for use in PPK analysis at weeks 2, 4, 6 11. Visual Attention and Executive Function will be measured by the Trail Making A and B Tests at screening, baseline, week 6 12. Sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI) at baseline, week 6 13. Assess the effect of Xanamem on trial participant perception of pain using the Brief Pain Inventory at baseline, week 6 |
| Overall study start date | 27/02/2023 |
| Completion date | 01/08/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 70 Years |
| Sex | Both |
| Target number of participants | 160 |
| Total final enrolment | 167 |
| Key inclusion criteria | 1. Male or female aged 18 to 70 years, inclusive at the time of Screening. 2. Positive MDD primary diagnosis confirmed by MINI at Screening. 3. Persistent depressive symptoms as determined by a HAM-D ≥ 17 at Screening. 4. Self-reported subjective cognitive dysfunction, as determined by an affirmative response to any aspect of a single-question test about perceived problems with their thinking. 5. On a stable dose of a first- or second-line antidepressant that is approved for the treatment of depression (but not a tricyclic antidepressant, monoamine oxidase inhibitor, or vortioxetine) drug for at least 6 weeks. 6. Exhibit a 0.5 SD impairment on the BASIC Boxfiller subtest relative to age, education, and gender relevant norms at Screening. 7. Body mass index (BMI) 17.5 to 38 kg/m2 inclusive at the time of Screening. 8. Must provide written informed consent to participate in the trial and be willing and able to comply with the requirements of the protocol and complete all trial visits. 9. Smokers of ≤ 5 cigarettes a day or equivalent nicotine (includes vaping) / tobacco products are eligible if they are willing to abstain from nicotine / tobacco products on the cognitive testing days. |
| Key exclusion criteria | 1. Active suicidal ideation (“yes” to any of questions 3, 4, or 5 on the C-SSRS and/or per Investigator assessment). 2. On a tricyclic antidepressant, monoamine oxidase inhibitor, esketamine, or vortioxetine. 3. Other comorbid psychiatric disorder of clinical concern, as determined by medical history and Screening assessments. 4. A history of clinically diagnosed dementia of any type. 5. A history of severe depression treated with electroconvulsive therapy. 6. Treatment with transcranial magnetic stimulation within the previous 3 months. |
| Date of first enrolment | 15/12/2022 |
| Date of final enrolment | 19/04/2024 |
Locations
Countries of recruitment
- Australia
- England
- United Kingdom
Study participating centre
United Kingdom
Sponsor information
Industry
59, St. Martin's Lane
Unit #218
London
WC2N 4JS
England
United Kingdom
| Phone | +44 1224 4334689 |
|---|---|
| raeg@axiom.cc |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 31/08/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Peer reviewed scientific journals Internal report Conference presentation Publication on website Submission to regulatory authorities All study data that is shared will be anonymised. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to commercial considerations, and due to the proof-of-concept nature of the trial. |
Editorial Notes
30/05/2024: The following changes were made to the study record:
1. Total final enrolment added.
2. The recruitment end date was changed from 31/05/2024 to 19/04/2024.
3. The overall study end date was changed from 31/12/2024 to 01/08/2024.
4. The intention to publish date was changed from 31/12/2025 to 31/08/2025.
05/09/2023: Internal review.
06/03/2023: Trial's existence confirmed by NHS HRA.
