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Trial registered on ANZCTR


Registration number
ACTRN12624000449538
Ethics application status
Approved
Date submitted
12/02/2024
Date registered
12/04/2024
Date last updated
21/05/2024
Date data sharing statement initially provided
12/04/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 2b double-blind, randomized, low-dose comparator-controlled clinical trial to assess the efficacy and safety of PEX010 in psilocybin-assisted psychotherapy for the treatment of adjustment disorder due to incurable cancer diagnosis
Scientific title
A Phase 2b double-blind, randomized, low-dose comparator-controlled clinical trial to assess the efficacy and safety of PEX010 in psilocybin-assisted psychotherapy for the treatment of adjustment disorder due to incurable cancer diagnosis
Secondary ID [1] 311523 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mental Health 332872 0
Incurable Cancer 333050 0
Adjustment Disorder 333051 0
Condition category
Condition code
Mental Health 329592 329592 0 0
Other mental health disorders
Cancer 329727 329727 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This Phase 2b study is a double-blind, 1:1:1 randomized, study to assess the efficacy, safety and tolerability of 25 mg, 10 mg and 1 mg [low-dose comparator] PEX010 in participants with adjustment disorder (AjD) following an incurable cancer diagnosis.
The study will consist of a combination of clinic visits and telehealth visits and will involve the following study sequence:
A screening visit (approximately 3 hours): within Day-28 to -2
Visit at the clinic for continued eligibility and baseline assessments: Day -1 (1-2 hours)
PAP cycle: Day 1 to Day 28
In Clinic Visits: Day 1, 13, 14, 15, 84
Telehealth appointments: Day 7, Day 21, Day 28, Day 56, Day 168 and Day 253

(Psychiatrist/Psychologist/Psychotherapist): Preparatory therapy session: Day 1, Day 7, Day 13 (approximately 1 hour) - Participants will attend three preparatory sessions (one virtual (Day 7) telehealth and two in-person (Day 1, Day 13)) in the two weeks prior to being treated with psilocybin. Face to face appointment at clinic to be conducted with a suitably trained therapist will occur on Day 1 and Day 13, whilst a telehealth appointment with the therapist will occur on Day 7. The therapist will support the participant to establish intentions and goals, to be prepared for a range of potential effects of the psilocybin and have sufficient information to approach the intervention with an open mind.

Face to face appointment at clinic to be conducted with a suitably trained therapist
(Psychiatrist/Psychologist/Psychotherapist). Drug administration: Day 14 (approximately 8 hours). Participants will receive a single administration of PEX010 (capsule) under medical supervision on Day 14. Participants will be supported through the acute effects of the psilocybin by a suitably qualified therapist who will be present throughout the drug-assisted session. For the majority of the session the participant will be encouraged to wear a headset with a playlist and a blindfold to encourage introspection. A mouth check will be conducted to ensure compliance with dosing.

Integration Session: Integration sessions will be conducted on Day 15 and Day 21 (approximately 1 hour). The Integration session on Day 15 will be a Face-to-face appointment at clinic to be conducted with a suitably trained therapist (Psychiatrist/Psychologist/Psychotherapist). An integration session occurring on day 21 will be conducted via telehealth with a suitably trained therapist. The integration sessions allow participants to process the experience of their drug-assisted session, consolidate changes into their perspective, reinforce insights from the therapy, and revisit issues that arose during the session. During the integration sessions, the therapist will facilitate the participant to reflect on their experiences of the psilocybin intervention, with the aim of translating their experiences into practical and accessible objectives.

Follow-up: Day 84 (week 12) (Clinic visit, approximately 1 hour) Eligible non-responders at Week 12 will be offered a second PAP cycle (at 25 mg PEX010 dose level). For eligible participants the second PAP cycle will include all activities from Day 13 onwards until Day 253. A maximum of 2 PAP cycles may be administered. To be conducted with a suitably trained therapist (Psychiatrist/Psychologist/Psychotherapist).
Final study follow-up

Follow-up Telehealth appointments (Approximately 1 hour): Day 168 (Month 3), Day 253 (Month 6) (calculated from the 12-week visit after the final PAP). To be conducted with a suitably trained therapist (Psychiatrist/Psychologist/Psychotherapist)
Session attendance checklists will be incorporated throughout the duration of the study to ensure compliance with all components of the intervention.
Intervention code [1] 327976 0
Treatment: Drugs
Comparator / control treatment
Low-dose comparator – 1mg PEX010
Oral capsule administration of low-dose comparator (1mg PEX010) with mouth checks to confirm compliance. The control group will also receive psychedelic assisted psychotherapy.
Control group
Dose comparison

Outcomes
Primary outcome [1] 337370 0
To assess the change in anxiety severity in participants with AjD due to an incurable cancer diagnosis, as measured by HAM-A.
Timepoint [1] 337370 0
Comparison between treatment groups in the change from baseline in the HAM-A total score at Week 12 after a single PAP cycle.
Primary outcome [2] 337372 0
To assess the safety and tolerability of a single dose of PEX010 (25 mg, 10 mg and 1 mg [low-dose comparator]) in people with AjD with an incurable cancer diagnosis.
Timepoint [2] 337372 0
Assessment of Day 14 (dosing day) vital signs (pre-dose and prior to discharge).

Primary outcome [3] 337534 0
To assess the safety and tolerability of a single dose of PEX010 (25 mg, 10 mg and 1mg [low-dose comparator]) in people with AjD with an incurable cancer diagnosis
Timepoint [3] 337534 0
Assessment of suicidality using the S-STS (baseline, Day 14 (dosing day), 4, 8, and 12-weeks and 6- and 9-months post-randomization).
Secondary outcome [1] 431598 0
To assess the change in anxiety severity after receiving PAP in participants with AjD and an incurable cancer diagnosis
Timepoint [1] 431598 0
Comparison between treatment groups after a single PAP cycle of change from baseline in the HAM-A total score at Day 15, Week 4, Week 8, and at 3- and 6-months post-treatment.
Secondary outcome [2] 431600 0
To assess the change in depression severity after receiving PAP in participants with AjD and an incurable cancer diagnosis.
Timepoint [2] 431600 0
Comparison between treatment groups after a single PAP cycle:
Change from baseline in HAM-D at Day 15, Week 4, Week 12, Week 8, and at 3- and 6-months post-treatment.
Secondary outcome [3] 431601 0
To assess the efficacy of PAP in changing severity of AjD for participants with an incurable cancer diagnosis.
Timepoint [3] 431601 0
Comparison between treatment groups after a single PAP cycle:
* Change from baseline in the ADNM-20 at Day 15, Week 4, Week 8, Week 12, and at 3- and 6-months post-treatment.
* Percentage of participants who achieve ‘remission’ of AjD defined by ADNM-20 score of 47.5 or less and Distress Thermometer Score <4 at Week 12 after 1 cycle.
* Percentage of participants who achieve ‘remission’ of AjD defined by ADNM-20 score of 47.5 or less and Distress Thermometer Score<4 at Week 12 after a 2nd cycle.
* Change from baseline in the Demoralization Scale at Day 15, Week 4, Week 8, Week 12, and at 3- and 6-months post-treatment.
Secondary outcome [4] 432242 0
To assess the change in depression severity after receiving PAP in participants with AjD and an incurable cancer diagnosis
Timepoint [4] 432242 0
Change from baseline in HADS at Day 15, Week 4, Week 8, Week 12 and at 3- and 6-months post-treatment.

Eligibility
Key inclusion criteria
To be eligible for study entry participants must satisfy all of the following criteria:
1. Screening AjD diagnosis (ICD-11), as defined by an ADNM-20 score greater than or equal to 47.5 , a score of greater than or equal to 4 on the Distress Thermometer and psychiatrist’s assessment via Mini International Neuropsychiatric Inventory (MINI).
2. Screening HAM-A Score greater than or equal to 18 (moderate anxiety).
3. Adults aged 18 to 80 years.
4. Diagnosed with incurable cancer (exempting those cancers listed in the exclusion criteria) and a minimum life-expectancy of 12 months in the opinion of the treating physician, with performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) scale.
5. Agrees not to commence any new psychiatric medications or psychotherapies from Screening to Week 12.
6. Able to communicate well and follow study procedures, judged as sufficiently competent with the English language by the investigator, able to build adequate rapport with study staff.
7. Judged to be of low suicide risk based on S-STS and the opinion of a research team psychiatrist.
8. Be medically suitable in the opinion of the investigator as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and blood tests.
9. Have access to a device that is compatible to use the digital technology, i.e smart-phone device, tablet, or iPad.
10. Agree not to take any sedating medications for a minimum of 12 hours before the dosing session including benzodiazepines, zopiclone, eszopiclone, zaleplon and zolpidem. Medications for cancer-related pain are permitted.
11. Must be willing and able to refrain from smoking throughout the duration of the dosing session. Nicotine replacement therapies may be permitted with the agreement of the medical monitor.
12. Agree that for one week before the psilocybin dosing session, participants will refrain from taking any illegal drugs or non-prescription medication (including cannabis, or CBD or THC containing products), nutritional supplement, or herbal supplement except when approved by the study investigators.
13. Participants taking any other medication that is not explicitly detailed as an excluded medication will be discussed with the investigator and medical monitor as appropriate. Decisions on inclusion will be based on clinical judgement and with sufficient justification provided.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Psychiatric Exclusion Criteria:
1. Current MDD (or within 12 months of Screening), current or past diagnosis of schizophrenia, psychotic disorder, unless this was substance-induced or resulting from a medical condition (e.g. lupus or malaria etc.), bipolar disorder I and II, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder, anti-social personality disorder or judged to be incompatible with establishment of rapport or safe exposure to psilocybin, as assessed through medical history and the MINI.
2. First-degree relative with a diagnosed psychotic disorder.
3. Scores from the screening psychiatrist and baseline S-STS that indicate that the participant is of clinically significant risk of suicide. A decision will be formed based on S-STS scores and used in combination with other clinically significant data at screening. Sites should refer to the medical monitor if required.
4. Has attempted suicide in the twelve months preceding the screening visit.
5. Current (<less than 1 year) alcohol or drug abuse as identified as moderate or severe during screening in accordance with DSM-5 criteria, using the MINI 7.0.2, not able or willing to abstain from alcohol consumption in the period 12 hours prior to the dosing session.
6. Any other reason that might prevent a participant from engaging in therapeutic preparation and integration sessions.
7. Previous use of psychedelics within 12 months preceding screening.

Medical Exclusion Criteria:
1. Diagnosed with brain metastases, glioblastoma, phaeochromocytoma, bowel obstruction or intestinal failure, active carcinoid syndrome, uncontrolled hypercalcemia, or uncontrolled diabetes mellitus or insipidus.
2. Currently taking or planning to take any of the following: lithium, any typical or atypical antipsychotic and monoamine-oxidase inhibitors. Participants with prior use of these medications must be willing to discontinue their use for at least 2 weeks prior to the baseline visit and to Day 28.
3. Currently taking or planning to take any anticonvulsant or mood stabilizer, including carbamazepine, lithium, phenytoin, and valproate. Participants with prior use of these medications must be willing to discontinue their use for at least 1 week prior to the baseline visit and to Day 28.
4. Participants who have taken selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (selective and norepinephrine reuptake inhibitor [SNRI] and selective serotonin reuptake inhibitor [SSRI]) within the last 3 months and/or who are planning to initiate them before Day 56 of their study participation.
5. Any form of fungal allergy.
6. Positive pregnancy test at screening, women who are breastfeeding or of childbearing potential who are unwilling or unable to use an effective form of contraception (or abstinence) for the study period and for 1 month post PEX010 dose will be excluded. Women will be required to conduct a serum pregnancy test at the in-person screening visit and urine test prior to dosing at the drug-assisted therapy session. Male participants who do not agree to use contraception for the study period and for 90 days post PEX010 dose to mitigate the risk of pregnancy will also be excluded.
7. A diagnosis of epilepsy or at significant risk of seizures based on medical history.
8. Cardiovascular conditions including stroke and/or myocardial infarction (less than one year before providing informed consent), uncontrolled hypertension (blood pressure greater than 140/90 mmHg) or clinically significant arrhythmia at screening. Results are exempt if they are a direct result of the participant’s cancer diagnosis and do not present a risk to administration of psilocybin, following discretion of the investigator.
9. Anyone who, at screening, has clinically significant findings on physical examination, including resting vital signs (HR below 40 or above 120 bpm, blood pressure below 90/60 or above 140/90), ECG (QTcF greater than 450 msec for males and greater than 470 for females), and positive alcohol breath test. Note: Testing for any out-of-range values may be repeated at the discretion of the Investigator.
10. Liver dysfunction as defined by results above 1.5 times the upper reference level. For participants with known Gilbert’s Syndrome results less than or equal to 3 times the upper reference level is permitted. Results are exempt if they are a direct result of the participant’s cancer diagnosis and do not present a risk to the administration of psilocybin, following discretion of the investigator.
11. Renal Function: estimated glomerular filtration rate less than 60 mL/min (calculated using Chronic Kidney Disease Epidemiology Collaboration) unless this is a direct result of the cancer diagnosis and does not present a risk to the administration of psilocybin, following the discretion of the investigator.
12. Any clinically significant laboratory abnormality(s) that in the opinion of the investigator would present a risk to the administration of psilocybin.
13. Any clinically significant renal, pulmonary, gastrointestinal, hepatic, or other illness that could affect the interpretation of results or be a potential health risk for the person if they were to be included in the study. Results are exempt if they are a direct result of the participant’s cancer diagnosis and do not present a risk to administration of psilocybin, following discretion of the investigator.
14. Below 18 or above 32 Body Mass Index (BMI) score.
15. Anyone with organic brain injury or diagnosed with any cognitive impairment.
16. Positive urine drug test for non-prescribed psychoactive substances at the dosing visit. Positive urine drug test for psychoactive substances at the in-person screening should be referred to the medical monitor. Note: Testing may be repeated once at the discretion of the Investigator.
17. Anyone on a research study of an investigational drug or who has been on a clinical trial within three months of enrollment.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed Opaque Envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
31/05/2024
Actual
Date of last participant enrolment
Anticipated
31/05/2025
Actual
Date of last data collection
Anticipated
28/02/2026
Actual
Sample size
Target
84
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 315814 0
Commercial sector/Industry
Name [1] 315814 0
Psyence Australia Pty Ltd
Country [1] 315814 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Psyence Australia Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 318085 0
None
Name [1] 318085 0
Address [1] 318085 0
Country [1] 318085 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314672 0
Bellberry Human Research Ethics Committee B
Ethics committee address [1] 314672 0
Ethics committee country [1] 314672 0
Australia
Date submitted for ethics approval [1] 314672 0
05/03/2024
Approval date [1] 314672 0
05/03/2024
Ethics approval number [1] 314672 0
2023-05-605

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 132358 0
Dr Philip Ryan
Address 132358 0
Vitalis Research Centre: 15, 456 St. Kilda Road, Melbourne VIC 3004
Country 132358 0
Australia
Phone 132358 0
+61 438 009 787
Fax 132358 0
Email 132358 0
[email protected]
Contact person for public queries
Name 132359 0
Dr Philip Ryan
Address 132359 0
Vitalis Research Centre: 15, 456 St. Kilda Road, Melbourne VIC 3004
Country 132359 0
Australia
Phone 132359 0
+61 438 009 787
Fax 132359 0
Email 132359 0
[email protected]
Contact person for scientific queries
Name 132360 0
Michelle Tusler
Address 132360 0
iNGENu CRO: Unit 22, 456 St Kilda Road, Melbourne, VIC 3004
Country 132360 0
Australia
Phone 132360 0
+61 390500654
Fax 132360 0
Email 132360 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.