Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000025538
Ethics application status
Approved
Date submitted
16/11/2023
Date registered
12/01/2024
Date last updated
12/01/2024
Date data sharing statement initially provided
12/01/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to assess two formulations of VLS-01 (VLS-01-IV and VLS-01-BU) in Healthy Adult Volunteers
Scientific title
A Phase 1b, Single-Centre, Open-Label Dose Ranging Study of an Optimized Formulation of VLS-01 in Healthy Adult Volunteers
Secondary ID [1] 310613 0
VLS-01-102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Depression 331493 0
Condition category
Condition code
Mental Health 328229 328229 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The participants will receive a total of 4 administrations of VLS-01 administered via IV (VLS-01 IV) in treatment period 1 and via buccal administration (VLS-01-BU) in treatment period 2 .

Dose:
VLS-01-IV: Single dose of 30 mg is a 57 minute IV infusion which will be administered by a registered nurse and monitored on site.


VLS-01-BU: Single doses of either 240mg or 160 mg, and 60 mg, and 20 mg with option to modify dose.. This is administered approximately 28 days after completion of treatment period 1..
Duration of administration; single day – until dissolved and monitored on site.
Dosage based on Phase 1a study. The Safety Monitoring Group (SMG) will review safety, tolerability, PK, and PD results, where available, after the last participant completes each of the first two doses of VLS-01-BU. The moderate and low doses may be modified by the SMG based on observed PK and PD to ensure that the three doses of VLS-01-BU produce a sufficient range of PK and PD effects

Dosing is performed on site under supervision of site staff.
Intervention code [1] 327018 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 336094 0
Assess the plasma PK of VLS-01-IV (IV infusion) and multiple doses of VLS-01-BU (buccal) and its 2 predominant metabolites (DMT-NO and IAA) .
Timepoint [1] 336094 0
Predose (within 2 h of dose) and 5, 10, 20, 30, 40, 50, 60, 90 (each ± 2 minutes), 120, 150, 180, 240, 360, and 480 minutes (each ± 10 minutes) after the start of treatment.
Primary outcome [2] 336853 0
Assess the urine PK of VLS-01-IV (IV infusion) and multiple doses of VLS-01-BU (buccal) and its 2 predominant metabolites (DMT-NO and IAA) .
Timepoint [2] 336853 0
Predose (within 2 hours before VLS-01 administration) and within 0 to 4 and 4 to 8 hours (both ± 30 minutes) after the start of treatment.
Secondary outcome [1] 427836 0
To assess the safety and tolerability of VLS-01 when administered as a single-dose of VLS-01-IV and multiple doses of VLS-01-BU in healthy adult participants.
Assessed as a composite secondary outcome.
Timepoint [1] 427836 0
Adverse events assessed from baseline until End of study visit (EOS)
Clinical labs at Screening, Predose and 6 hours post dose on Day 1, safety follow up and at End of study
Oral examination is done at Screening and on IP administration days.
Vital signs collected at Predose (within 2 h of dose) and 0.25, 0.5, 0.75, 1 h (plus or minus 5 minutes), 1.5, 2, 3, 4, and 6 h (plus or minus 15 minutes) post dose
ECG done at Predose, 4 hour and 6 hours post dose
C-SSRS administered at Screening, predose and 6h post dose on IP administration days, Safety follow up, and End of study (EoS)

Eligibility
Key inclusion criteria
Participants are eligible to be included in the study only if all the following criteria apply:
1. Participant must be 18 to 65 years of age (inclusive) at the time of signing the informed consent.
2. Participants who are overtly healthy as determined by medical history, physical examination, vital sign measurements, electrocardiogram (ECG), and laboratory safety tests performed at the Screening Visit and or before the first dose of IMP.
3. Participants who are not lactating or pregnant as confirmed by a serum pregnancy test at Screening and negative urine pregnancy test before dosing (applies only to participants of childbearing potential [POCBP]).
4 Body weight no greater than 100 kg and body mass index (BMI) within the range 20-32 kg per m2 (inclusive) at Screening.
5.Participant agrees to comply with using a double barrier method of contraception or sexual abstinence and not donate sperm or ova.
6. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
7. Smoke no more than 8 cigarettes, pipes, cigars, e-cigarettes or equivalent per month, including nicotine products, from 3 months prior to Screening and is willing to abstain from smoking/using nicotine products for 24 hours before VLS-01 administration and
during the entire dosing Visit.
8. Agrees to be available for all study Visits and cooperates fully with the requirements of the study protocol, including the Schedule of Assessments.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants are excluded from the study if any of the following criteria apply:

1. Current or past history schizophrenia or other psychotic disorders, or bipolar I or II disorder, has a past or current history of a significant mental, behavioral, or neurodevelopmental disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition including, but not limited to, diagnoses of: organic, including symptomatic, mental disorders; mental and behavioral disorders due to psychoactive substance use; schizophrenia, schizotypal, and delusional disorders; mood (affective) disorders (only current diagnosis exclusionary); neurotic, stress-related and somatoform disorders; or disorders of adult personality and behavior.
2. Has a mild, moderate, or severe substance use disorder (drug or alcohol) within the 6 months before Screening and/or history of moderate or severe substance use disorder (drug or alcohol) within the previous 5 years before Screening.
3. Has homicidal ideation or intent per the investigator’s clinical judgment.
4. Risk of suicide as determined by Columbia Suicide Severity Scale (C-SSRS).
5. Has a history of clinically significant cardiovascular, cerebrovascular, or peripheral vascular disease, including but not limited to unstable angina, myocardial infarction, congestive heart failure, cardiac arrhythmia, hypertension, hypotension, bradycardia, or tachycardia.
6. History of seizures, convulsions or increased intra-cranial pressure except for pediatric febrile seizures.
7. Has an active malignancy, or history of malignancy, excluding basal or squamous cell carcinoma of the skin, within 2 years before Screening.
8. History of risk factors including hypokalemia or a family history of Long QT Syndrome.
9. Has clinically relevant long-term coronavirus disease-2019 (COVID-19) symptoms or current signs or symptoms of COVID-19.
10. Has a biological 1st degree relative with schizophrenia, bipolar I/II, and/or psychotic disorder (unless induced by substance or medical condition).
11. Has a history of greater than 25 lifetime administrations of psychedelic drugs, and/or last use of a psychedelic drug within 6 months before Screening and/or has reported HPPD or other significant AEs after prior use of hallucinogens
12. Is unable or unwilling to refrain from using any recreational psychoactive drugs (other than tobacco and nicotine products), including alcohol, from 24 hours before the start of IMP infusion until 24 hours after dosing has been completed on dosing days.
13. Is unable or unwilling to refrain from using tobacco and nicotine products for 24 hours before the start of IMP administration until the end of the dosing Visit on each dosing day.
14. Has donated blood or plasma within 30 days before Screening, lost more than 500 mL of whole blood within the 30 days before Screening, or received a blood transfusion within 1 year before Screening

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Pharmacokinetics / pharmacodynamics
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2024
Actual
Date of last participant enrolment
Anticipated
26/02/2024
Actual
Date of last data collection
Anticipated
4/06/2024
Actual
Sample size
Target
16
Accrual to date
Final
Recruitment outside Australia
Country [1] 25773 0
New Zealand
State/province [1] 25773 0
Auckland

Funding & Sponsors
Funding source category [1] 314826 0
Commercial sector/Industry
Name [1] 314826 0
atai Therapeutics Pty. Ltd.
Country [1] 314826 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
atai Therapeutics Pty. Ltd.
Address
330 Collins Street Melbourne Victoria 3000 Australia
Country
Australia
Secondary sponsor category [1] 316818 0
None
Name [1] 316818 0
Address [1] 316818 0
Country [1] 316818 0
Other collaborator category [1] 282813 0
Commercial sector/Industry
Name [1] 282813 0
Novotech (New Zealand) Limited
Address [1] 282813 0
Level 6, 2-6 Crowhurst Street, Newmarket, Auckland, 1023, New Zealand
Country [1] 282813 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313832 0
Central Health and Disability Ethics Committees
Ethics committee address [1] 313832 0
Ministry of Health, 133 Molesworth Street PO Box 5013, Wellington 6011, New Zealand
Ethics committee country [1] 313832 0
New Zealand
Date submitted for ethics approval [1] 313832 0
12/09/2023
Approval date [1] 313832 0
15/12/2023
Ethics approval number [1] 313832 0

Summary
Brief summary
Depression and anxiety are common mental health disorders that result in individual suffering and have a significant socio-economic impact. In New Zealand, approximately 1 in 7 people will experience depression during their lifetime. Traditional antidepressants often take weeks to months to positively affect mood but are ineffective in approximately 30% of all patients, which often leads to treatment resistant
depression (TRD). Treatment of TRD is difficult and may include different pharmacological treatments, or brain stimulation therapies (which are often accompanied by intolerable side effects). However, no single treatment is effective for all TRD patients and there is a significant medical need for effective TRD therapies that are fast-acting and less invasive.

As such, there is an urgent need to improve and expand therapeutic options for these TRD patients. This study will provide critical data and will inform the ongoing development of VLS-01 in the treatment of TRD.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 129486 0
Dr Christian Schwabe
Address 129486 0
Auckland Clinical Studies (ACS) 3 Ferncroft Street, Grafton, Auckland, 1010 New Zealand
Country 129486 0
New Zealand
Phone 129486 0
+64 93733474
Fax 129486 0
Email 129486 0
christian@clinicalstudies.co.nz
Contact person for public queries
Name 129487 0
Dr Christian Schwabe
Address 129487 0
Auckland Clinical Studies (ACS) 3 Ferncroft Street, Grafton, Auckland, 1010 New Zealand
Country 129487 0
New Zealand
Phone 129487 0
+64 93733474
Fax 129487 0
Email 129487 0
christian@clinicalstudies.co.nz
Contact person for scientific queries
Name 129488 0
Dr Christian Schwabe
Address 129488 0
Auckland Clinical Studies (ACS) 3 Ferncroft Street, Grafton, Auckland, 1010 New Zealand
Country 129488 0
New Zealand
Phone 129488 0
+64 93733474
Fax 129488 0
Email 129488 0
christian@clinicalstudies.co.nz

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


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.