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Trial registered on ANZCTR


Registration number
ACTRN12622000851763
Ethics application status
Approved
Date submitted
31/05/2022
Date registered
16/06/2022
Date last updated
14/11/2022
Date data sharing statement initially provided
16/06/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
VLS-01-101: A study to assess Two formulations of VLS-01 (VLS-01 BU and VLS-01-IV) in healthy participants
Scientific title
A phase 1,First-in-Human, open-label, Safety, Tolerability and Pharmacokinetic Study of Single-Ascending Doses of VLS-01 in Healthy Adult Volunteers
Secondary ID [1] 306973 0
VLS-01-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Treatment resistant Depression (TRD) 326089 0
Condition category
Condition code
Mental Health 323400 323400 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
VLS-01 is being developed as a potential anti-depressant treatment for Treatment-resistant depression (TRD). This Phase 1 study will investigate the effects of VLS-01 in healthy participants, when administered buccally (between the cheeks and gums) as “VLS-01-BU” and when administered via intravenous infusion (infusion into the vein) as “VLS-01-IV”.
The study will be comprised of two parts (Part 1 and Part 2) and will include 48 healthy participants, from New Zealand Clinical Research (NZCR). Part 1 will be comprised of 8 participants, all of whom will receive a single 30mg dose of VLS-01 as an intravenous (IV) infusion (VLS-01-IV). Part 1 will be split into 2 groups of 4 participants each, and all safety and pharmacokinetic (PK) data from the first 4 participants will be reviewed before enrolling the remaining 4 participants in Part 1.
Part 2 will be consist of 5 cohorts, with each cohort being comprised of 8 participants each. The cohorts within Part 2 will enroll in sequential order, and depending on when participants join the study, they will enroll in either Cohort 1, 2, 3, 4, or 5 to receive 10mg, 25mg, 45mg, 65mg, or 80mg, respectively. Participant's in Part 2 will receive a single dose of VLS-01 (at the respective dose) via the buccal route (a thin buccal strip(s) placed between the cheeks and gums). After the last participant in each cohort has dosed, all available safety data will be reviewed by the Safety monitoring group (SMG) to determine whether to proceed to the next cohort. Part 1 and 2 will run parallel to each other and the next cohort will not begin until SMG review has been completed and it is confirmed dosing can continue. The stategies that will used to monitor adherance to the intervention would be monitored dosing where all doses of VLS-01-IV and VLS-01-BU will be administered in the presence of the Investigator or their designee.
Intervention code [1] 323413 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 331141 0
To assess the safety and tolerability of VLS-01 when administered as single-ascending doses of a buccal formulation (VLS-01-BU) and an intravenous formulation (VLS-01-IV) in healthy adult participants. This will be assessed by checking the frequency and severity of Adverse events (AEs), oral examination (participants in Part 2 only) and also by safety laboratory results. Adverse events will be assessed by symptom focused physical and clinical examination of any autonomic responses that the participant would report from screening to End of study. Vital signs that are assessed include blood pressure (BP), Heart rate, Respiratory rate and Temperature. BP will be assessed using a sphygmomanometer and temperature will be recorded. Clinical laboratory tests and safety labs will use both blood and urine samples.
Suicidal ideation will be measured by Columbia suicide severity rating scale (C-SSRS) score (Baseline to EOS visit on Day 8).
Timepoint [1] 331141 0
Partipants will be assessed daily for adverse events from baseline to end of study visit on Day 8. Participants in Part 2 will have an additional oral examination on screening, Day -1, Day 1 and End of Study/Day 8. All other safety measures for Part 1 and 2 are the same.
Secondary outcome [1] 408955 0
To assess the plasma (PK) characteristics of VLS-01-BU and VLS-01-IV and its 2 predominant metabolites (DMT-NO and IAA) following single-ascending doses in healthy adult participants. Plasma PK parameters including Tmax, Cmax, AUC0-t, AUC0-24, AUC0-24, AUC0-inf, AUC%extrap, Kel, t½ [VLS-01-IV] or apparent t½ [VLS-01-BU], CL or CL/F, Vz/F or Vz, dose normalized Cmax, dose normalized AUC0-t, dose normalized AUC0-4, dose normalized AUC0-inf, and metabolite to parent ratios.
Timepoint [1] 408955 0
On Day 1, plasma samples for PK will be collected predose (within 1 hour before VLS-01 administration). Part 1 samples will be collected at 3, 6, 8, 11, 15, 20, 23, 25, 29, 35, 45, 55, 65 (all ± 1 minute), and 240 minutes (± 10 minutes) after the start of VLS-01-IV administration.
Part 2 samples will be collected at 5, 10, 15, 20, 30, 40, 50, 60 minutes (all ± 2 minutes), 1.5, 2, 4, 8, and 24 hours (all ± 10 minutes) after the start of VLS-01-BU administration. The 24-hour sample for Part 2 will be collected before discharge from the CRU on the morning of Day 2.
Secondary outcome [2] 408956 0
To assess the urine pharmacokinetic (PK) characteristics of VLS-01-BU and VLS-01-IV and its 2 predominant metabolites (DMT-NO and IAA) following single-ascending doses in healthy adult participants. Urine PK parameters includes Ae, Fe, and CLR.
Timepoint [2] 408956 0
On Day 1, urine for PK analysis will be obtained within 2 hours before VLS-01 administration (predose ) and at intervals 0 to 4, 4 to 8, 8 to 12, and 12 to 24 hours (all ± 30 minutes) from the start of VLS-01 administration.

Eligibility
Key inclusion criteria
1. Male or female 21 to 45 years of age, inclusive, at time of consent.
2. Female participants must have a negative serum pregnancy test result at Screening and a negative urine pregnancy test at admission to the CRU, are not currently breast-feeding, and must meet one of the following criteria:
a. Undergone 1 of the following sterilization procedures at least 6 months before the first
dosing:
i. hysteroscopic sterilization
ii. bilateral tubal ligation or bilateral salpingectomy
iii. hysterectomy
iv. bilateral oophorectomy
v. Essure sterilization; or
b. Be postmenopausal with amenorrhea for at least 1 year before the first dosing and follicle-stimulating hormone (FSH) serum levels consistent with postmenopausal status.
c. Female participants of childbearing potential must use at least one of the following protocol-specified highly effective methods or effective methods of birth control and must agree to use barrier contraception (male condom) during heterosexual intercourse, from the time of Screening until at least 90 days after VLS-01 administration as described in the protocol..
3. Participant weighs more than or equal to 50 kg and less than or equal to 100 kg and has a body mass index (BMI) more than or equal to 18.0 kg/m2 and less than or equal to 32.0 kg/m2, inclusive, at Screening.
4. Participants who smoke no more than 2 cigarettes, pipes, cigars, e-cigarettes or equivalent per week, including nicotine products, can be included in the study but must be willing to abstain from smoking/using nicotine products for 24 hours before VLS-01 administration and during the confinement period.
Minimum age
21 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participants who meet any of the following criteria will be excluded from this study:
1. Known allergy or hypersensitivity to VLS-01-BU and VLS-01-IV (DMT) or any of the excipients in the formulation.
2. 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. and as determined by the protocol.
3. History of seizures, convulsions, or increased intra-cranial pressure with the exception of pediatric febrile seizures.
4. Poor venous access for participants administered VLS-01-IV, or participants with existing buccal lesions or abnormalities that could confound the oral administration of VLS-01-BU or the oral examination.
5. Has an active malignancy, or history of malignancy, excluding basal or squamous cell carcinoma of the skin, within 2 years before screening.
6. Positive test results for hepatitis B surface antigen, hepatitis C virus antibody, or anti-human immunodeficiency virus (HIV) type 1 antibody; participants with prior recovered HBV infection will be included with confirmed normal liver function tests; and participants with positive hepatitis C virus antibody results, but who have been effectively treated for hepatitis C as evidenced by a negative hepatitis C ribonucleic acid (RNA) confirmation test, and who no longer require antiviral therapy, are eligible for participation.
7. Has taken compound(s) known to induce or inhibit cytochrome P450 (CYP) drug metabolizing enzymes (eg, rifampin, cimetidine, or barbiturates) within 30 days before dosing, including herbal supplements, grapefruit juice or products, Seville orange juice or related products, or St. John’s wort.
8. Has received a monoamine oxidase inhibitor within 14 days of screening.
9. Has received treatment with another investigational drug, investigational device, or approved therapy for investigational use within 30 days or 5 half-lives (whichever is longer) before dosing; prior participation at any time in non-invasive methodology trials in which no drugs were given is acceptable.
10. Has donated blood or plasma within 30 days before screening, or had a loss of whole blood of more than 500 mL within the 30 days before screening, or receipt of a blood transfusion within one year before screening.
11. Has experienced symptoms of acute illness or chronic disease within 14 days before Screening, or any disease or condition (medical or surgical) that, by the determination of the PI, might compromise interpretation of safety or PK data, or would place the participant at risk as a result of participation in the study.

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
Parallel
Other design features
Not applicable
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
As this study has a Phase 1 single-ascending dose (SAD) design, it is not powered for inferential statistics. This sample size is commonly used in studies of this design to obtain sufficient information on the safety and PK before progressing to subsequent studies.

Evaluation of safety will be performed on the Safety Population. Safety data that will be evaluated include AEs, assessment of suicidality, clinical laboratory results, vital signs and continuous pulse oximetry, physical examinations, oral examination (Part 2 only), and ECGs.

Pharmacokinetic parameters will be computed from the individual plasma and urine concentrations using a non-compartmental approach using validated Phoenix WinNonlin® software (Version 8.3 or higher, Certara, USA).


Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/09/2022
Actual
6/10/2022
Date of last participant enrolment
Anticipated
13/01/2023
Actual
Date of last data collection
Anticipated
23/01/2023
Actual
Sample size
Target
48
Accrual to date
8
Final
Recruitment outside Australia
Country [1] 24733 0
New Zealand
State/province [1] 24733 0
Auckland

Funding & Sponsors
Funding source category [1] 311285 0
Commercial sector/Industry
Name [1] 311285 0
Viridia Life Sciences Australia Pty Ltd
Country [1] 311285 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Viridia Life Sciences Australia Pty Ltd
Address
Viridia Life Science Australia Pty Ltd, 58 Gipps Street, Collingwood, Victoria, 3066
Country
Australia
Secondary sponsor category [1] 312649 0
None
Name [1] 312649 0
Address [1] 312649 0
Country [1] 312649 0
Other collaborator category [1] 282265 0
Commercial sector/Industry
Name [1] 282265 0
Novotech (New Zealand) Limited
Address [1] 282265 0
Level 6, 2-6 Crowhurst Street, Newmarket, Auckland, 1023, New Zealand
Country [1] 282265 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310792 0
Central Health and Disability Ethics Committees (HDEC)
Ethics committee address [1] 310792 0
Health and Disability Ethics Committees, Minisitry of Health, 133 Molesworth Street
PO Box 5013, Wellington 6011
Ethics committee country [1] 310792 0
New Zealand
Date submitted for ethics approval [1] 310792 0
12/04/2022
Approval date [1] 310792 0
05/05/2022
Ethics approval number [1] 310792 0
2022 Full 12523

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 118882 0
Dr Christian Schwabe
Address 118882 0
New Zealand Clinical Research, 3 Ferncroft Street Grafton, Auckland 1010, New Zealand
Country 118882 0
New Zealand
Phone 118882 0
+64 021 873 974
Fax 118882 0
Email 118882 0
christian@clinicalstudies.co.nz
Contact person for public queries
Name 118883 0
Dr Christian Schwabe
Address 118883 0
New Zealand Clinical Research, 3 Ferncroft Street Grafton, Auckland 1010, New Zealand
Country 118883 0
New Zealand
Phone 118883 0
+64 9 373 3474
Fax 118883 0
Email 118883 0
christian@clinicalstudies.co.nz
Contact person for scientific queries
Name 118884 0
Dr Christian Schwabe
Address 118884 0
New Zealand Clinical Research, 3 Ferncroft Street Grafton, Auckland 1010, New Zealand
Country 118884 0
New Zealand
Phone 118884 0
+64 9 373 3474
Fax 118884 0
Email 118884 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


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.