Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000876493p
Ethics application status
Submitted, not yet approved
Date submitted
10/06/2025
Date registered
12/08/2025
Date last updated
12/08/2025
Date data sharing statement initially provided
12/08/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
A 12-participant study in depressed patients collecting CSF (Cerebrospinal fluid) to study the pharmacodynamic biomarkers of EVX-301 (L-5 Hydroxytryptophan in Saline) over a 24 hour infusion period.
Scientific title
A Phase 1b, Randomized, Double-Blind, Placebo-Controlled Evaluation of selected Pharmacodynamic Biomarkers in Cerebrospinal Fluid (CSF) Following 24-hour Intravenous Infusion of EVX-301 in Adults with Depression Receiving Stable Antidepressant Treatment
Secondary ID [1] 314453 0
None
Universal Trial Number (UTN)
U1111-1322-7965
Trial acronym
N/A
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Depression 337670 0
Condition category
Condition code
Mental Health 334005 334005 0 0
Depression

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure

CSF Sampling Process is as follows:
Anaesthesia-trained staff will perform the Lumber Punctures (LPs), using anaesthetic equipment and procedures.
LP will be performed twice - pre-dose and post 24 hr infusion.
Aseptic techniques will be used.
The sitting position will be used
Lignocaine will be delivered to provide skin anaesthesia.
By default a 25G pencil point needle will be used.
The inital few drops of CSF will be discarded, and the subsequent volume placed in Eppendorf, or similar, tubes for storage.
It is anticipated the procedure will take 15 minutes.
Subjects will be cared for supine for 1-2 hours post procedure.

Active Treatment is a.24-hr Intravenous (IV) infusion of EVX-301 (L-5 Hydroxytryptophan in Saline). The infusion rate will be continuous based on weight to achieve (approx 41.6ml/hr) 1mg/kg of EVX-301 infused over a 24 hr period.
Intervention code [1] 331189 0
Treatment: Drugs
Comparator / control treatment
Control treatment is 0.1% Normal Saline infused IV over 24 hrs
Volume of infusion is approximately 1L or 1000ml of saline at 41.7ml/hr.
Control group
Placebo

Outcomes
Primary outcome [1] 341739 0
Assess the safety and tolerability of a single 1 mg/kg 24-hour infusion of EVX-301 in participants with a diagnosis of depression taking a stable therapeutic dose of Selective Serotonin Reuptake Inhibitor (SSRI) or Selective Norepinephrine Reuptake Inhibitor (SNRI) This outcome will be assessed as a composite of all of the safety and tolerability parameters.
Timepoint [1] 341739 0
Safety and tolerability parameters will be assessed at baseline and at the end of the 24-hr infusion period of the IP EVX-301.
Primary outcome [2] 341740 0
Assess the effect of a single constant-rate 24-hour infusion of EVX-301 (5-HTP 1 mg/kg/24h) on CSF levels of 5-hydroxytryptophan (5-HTP), 5-hydroxyindoleacetic acid (5-HIAA), and serotonin (aka 5-hydroxytryptamine, 5-HT) in participants with a diagnosis of depression taking a SSRI or SNRI. This will be assessed as a composite outcome.
Timepoint [2] 341740 0
CSF samples will be collected at pre-dose (Baseline, 0h) and at end of the infusion (24h)
Secondary outcome [1] 448572 0
Determine plasma/serum levels of 5-HTP resulting from a constant-rate 24-hour infusion of EVX-301 (1 mg/kg/24h) in participants with a diagnosis of depression taking a stable therapeutic dose SSRI or SNRI.
Timepoint [1] 448572 0
Plasma samples will be collected to determine 5-HTP concentrations at pre-dose (0h) and at periodic intervals during the infusion (4h, 6h, 24h before stopping the infusion).
Secondary outcome [2] 448573 0
Determine mean change in serum cortisol levels resulting from a single 1 mg/kg constant-rate 24-hour infusion of EVX-301 in participants with a diagnosis of depression taking a stable therapeutic dose SSRI or SNRI.
Timepoint [2] 448573 0
Serum will be collected at baseline (0h/predose) and at 1h and 2h during the infusion

Eligibility
Key inclusion criteria
Inclusion Criteria Participants who meet all the following inclusion criteria may be included in the study:

1. Male or female healthy participants, aged 18-65 years inclusive at Screening;
2. Diagnosed with Depression and confirmed via documentation from treating physician.
3. Taking a SSRI or SNRI at a TGA-approved dose regimen for at least the past 4 weeks at the time of Screening.
4. Weight between 50 kg and 125 kg, with Body mass index (BMI) of 18.0 kg/m2 to 40.0 kg/m2 at Screening.
5. Must agree not to use tobacco or any tobacco containing products use during the clinic in-patient stay.
6. All male participants must agree to refrain from donating sperm and abstain from sexual intercourse or use a highly effective method of birth control with partners of childbearing potential during the study and for 90 days after investigational product dosing.
a. Use of a highly effective method of birth control in male participants includes vasectomy or the use of a condom in combination with either barrier methods, hormonal birth control or Intrauterine Device (IUD) by the female partner.
7. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
a. Not of childbearing potential, defined as surgically sterile (documented hysterectomy, bilateral salpingectomy or bilateral oophorectomy) or postmenopausal (no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient);
b. Of childbearing potential and agrees to use a highly effective method of contraception consistently during the treatment period and for at least 90 days following completion of study.
8. Females of childbearing potential must have a negative pregnancy test at Screening (serum) and Day -1 (urine).
9. The participant must voluntarily provide written informed consent prior to any study procedures being performed and is willing and able to comply with procedures required in this protocol.
10. Be willing and able to remain in the study unit for the entire duration of the in-patient portion of the study.
11. Clinical laboratory findings and vital signs within normal reference ranges, or if outside of the normal reference ranges, deemed not clinically significant by the Investigator. PI/ designee can retest laboratory samples or vital signs at their discretion.
a. Systolic blood pressure between 90-140 mmHg (inclusive) and a diastolic blood pressure between 60-90 mmHg (inclusive)
b. Resting pulse rate between 50-100 beats per minute
12. The participant is in good general health, with the exception of the presenting condition under study, as determined by medical history, physical examination, ECG, serum chemistry and hematology, urinalysis and serology.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Any of the following will exclude potential participants from the study:

1. History of needing to stop any previous SSRIs or SNRI due to intolerable side effects.
2. History of a diagnosis of serotonin toxicity or presence of serotonin toxicity per the Hunter Serotonin Toxicity Criteria at Screening.
3. Expressing desire to modify, stop current SSRI or SNRI medication, or participant has indicated poor adherence with current SSRI or SNRI medication.
4. Any psychiatric hospitalization within 30 days of Screening.
5. Current suicidal ideation with intent to act, either with or without a plan (SI score >2 on the C-SSRS - Screening version.)
6. A suicide attempt within 6 months prior to Screening, or self-harm behavior within 30 days prior to Screening.
7. Current use of monoamine oxidase inhibitors, triptans, serotonin agonists (including vortioxetine, vilazodone, and buspirone), serotonin antagonists (except 5-HT3/serotonin 3 receptor antagonists as anti- emetic rescue medication at the discretion of the PI, if clinically warranted), antipsychotics, anticonvulsants, atypical antidepressants, tricylic antidepressants, NMDA receptor antagonists (e.g., esketamine), psychostimulants, or daily long-term use of tramadol/other opioid analgesics within 14 day or five half-lives (i.e., 1-2 days or 5-7 days, respectively), prior to start of dosing (whichever is longer).
8. Documented lifetime diagnosis of schizophrenia spectrum and/or other psychotic disorders, bipolar disorder, seizure disorder, intellectual developmental disorder, or schizotypal, schizoid disorders according to the DSM-5.
9. Current diagnosis of post-partum depression, depression with psychotic features, delirium, major or mild neurocognitive disorder (per DSM- 5), or anorexia nervosa.
10. Other comorbid anxiety disorders (e.g., obsessive-compulsive disorder, posttraumatic stress disorder, generalized anxiety disorder, social anxiety disorder) are permitted if it is in addition the participant’s primary diagnosis of depression and at the discretion of the Investigator.
11. History of alcohol abuse and/or regular use of more than 2 units of alcohol per day or > 21 units per week for males and > 14 units for females and/or positive alcohol breath test results (Note: one unit of alcohol equals 250 mL beer, 125 mL wine or 25 mL spirits).
12. Current use of opioid medications. Use of hallucinogens during the 30 days prior to Day 1.
13. Likely to have difficulty tolerating venipuncture, or an infusion of 24 hours duration.
14. Clinically significant history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, immunologic or neurologic disorder that, in the opinion of the Investigator and medical monitor or designee, would pose a risk to participants safety or interfere with the study evaluation, procedures, or completion.
15. Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinoma of the skin that has been resected and no further treatment is required.
16. History of any known severe drug or excipient allergy (e.g., anaphylaxis), including known sensitivity to any of the study intervention components, plain lignocaine or other hypersensitivity that, in the opinion of the Investigator, contraindicates participation in the study.
17. Alanine transaminase (ALT) or aspartate transaminase (AST) >2.0 x upper limit of normal (ULN); or INR > 1.5 or APTT > 40 seconds or Platelets < 50 x 109/L.
18. Total bilirubin >1.5 x ULN.
19. A 12-lead ECG with a clinically significant abnormality at Screening, Day -1 (Admission) or Day 1, as judged by the Investigator, including, but not limited to, a QTc >450 msec for male participants or >470 msec for female participants using Fridericia’s formula (QTcF).
20. Testing positive for hepatitis B, hepatitis C, or HIV, or history of any of these illnesses (with the exception of treated hepatitis C with negative viral PCR).
21. Having initiated any prescription or nonprescription (over-the-counter) medication within 7 days, or five half-lives, prior to start of dosing (whichever is longer). Permitted concomitant medications include analgesics (paracetamol), hormonal contraceptives, hormonal replacement therapy, non-sedating antihistamines or any chronic medications taken for treatment of stable, controlled illnesses that are not anticipated to deteriorate during the course of the study. Topical medications may be allowed at the discretion of the Investigator.
22. Use of any herbal/dietary supplement containing 5-HTP or St. John’s Wort within 7 days, or five half-lives (i.e., 1-2 days or 5-7 days, respectively), prior to start of dosing (whichever is longer).
23. Current enrollment or recent participation in any other clinical study involving an investigational study intervention or any other type of medical research (including device or non-interventional studies) within the last 30 days or five half-lives of the investigational drug, device, or biologic before dosing, whichever is longer.
24. Positive urine drug screen (excludes cannabinoids and Benzodiazepines) or alcohol breath test present at Screening and Day -1 (Admission).
25. Donation or loss of greater than 0.5 L of blood within 90 days before Screening or study start. Donation of platelets within 40 days before Screening or study start. Donation of plasma within 14 days before Screening or study start. Receipt of blood products within 60 days before Screening or study start.
26. Known poor peripheral venous access, e.g., from previous or current procedures such as venipuncture, that could potentially limit ability to complete any protocol stipulated procedures

Additional Exclusion criteria relating to Lumbar puncture/serial CSF sampling:
27. Lower spinal malformations, local infection, signs of increased intracranial pressure, or other abnormalities that would exclude lumbar puncture.
28. History of head injury with loss of consciousness, or headaches or migraines, deemed to be clinically significant by the Investigator.
29. Evidence of history of clinically significant back pain or back injury that would interfere with study procedures. Participants with back pain that is treated and manageable can be allowed in the study, per PI discretion.
30. Evidence or history of significant active bleeding or coagulation disorder.

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)
central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Factorial
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
25/08/2025
Actual
Date of last participant enrolment
Anticipated
28/10/2025
Actual
Date of last data collection
Anticipated
25/11/2025
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 28031 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 44234 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 318991 0
Commercial sector/Industry
Name [1] 318991 0
Evecxia Therapeutics, Inc.
Country [1] 318991 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Evecxia Therapeutics, Inc.
Address
Country
United States of America
Secondary sponsor category [1] 321456 0
None
Name [1] 321456 0
Address [1] 321456 0
Country [1] 321456 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 317596 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 317596 0
Ethics committee country [1] 317596 0
Australia
Date submitted for ethics approval [1] 317596 0
04/08/2025
Approval date [1] 317596 0
Ethics approval number [1] 317596 0

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

Contacts
Principal investigator
Name 141530 0
Prof Guy Ludbrook
Address 141530 0
PARC Clinical Research Level 4G.1, East Wing, Royal Adelaide Hospital Port Road, Adelaide South Australia, Australia 5000
Country 141530 0
Australia
Phone 141530 0
+61 413 817 901
Fax 141530 0
Email 141530 0
[email protected]
Contact person for public queries
Name 141531 0
Guy Ludbrook
Address 141531 0
PARC Clinical Research Level 4G.1, East Wing, Royal Adelaide Hospital Port Road, Adelaide South Australia, Australia 5000
Country 141531 0
Australia
Phone 141531 0
+61 08 8206 8888
Fax 141531 0
Email 141531 0
[email protected]
Contact person for scientific queries
Name 141532 0
Guy Ludbrook
Address 141532 0
PARC Clinical Research Level 4G.1, East Wing, Royal Adelaide Hospital Port Road, Adelaide South Australia, Australia 5000
Country 141532 0
Australia
Phone 141532 0
+61 08 8206 8888
Fax 141532 0
Email 141532 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
• Requires a data sharing agreement between data requester and trial custodian or sponsor
What individual participant data might be shared?
• All de-identified individual participant data
What types of analyses could be done with individual participant data?
• Systematic reviews and meta-analyses
• Studies exploring new research questions
• Health economic analyses
• Studies testing whether findings can be repeated or confirmed
• Teaching research methods or developing new statistical techniques
When can requests for individual participant data be made (start and end dates)?
From:
After publication of main results
To:
Not yet decided
Where can requests to access individual participant data be made, or data be obtained directly?
• Email of trial custodian, sponsor or committee: [email protected]


Are there extra considerations when requesting access to individual participant data?
No


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.