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Trial registered on ANZCTR


Registration number
Help: Registration number
ACTRN12626001348347
Ethics application status
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Approved
Date submitted
Help: Date submitted
13/10/2026
Date registered
Help: Date registered
10/11/2026
Date last updated
Help: Date last updated
10/11/2026
Date data sharing statement initially provided
Help: Data sharing statement date
10/11/2026
Type of registration
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Prospectively registered

Titles & IDs
Public title
A Phase 1, Randomized, Double-blind, Placebo-controlled, First-in-human Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of AKV9 in Healthy Adults
Scientific title
A Phase 1, Randomized, Double-blind, Placebo-controlled, First-in-human Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of AKV9 in Healthy Adults
Additional trial identifiers [1] 318514 0
AKV9-3001AU
Universal Trial Number (UTN)
Trial acronym
Related trial records

Health condition
Health condition(s) studied:
Amyotrophic lateral sclerosis 343696 0
Condition category
Condition code
Neurological 339813 339813 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of the intervention or exposure
The proposed study is a 2-part, single-center, randomized, double-blind, placebo-controlled, first-in-human study to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending doses of AKV9 in approximately 72 healthy adult participants.

Part A will consist of a total of approximately 56 male and female healthy adult participants will be enrolled in a total of 7 sequential treatment cohorts to receive a single, oral dose of AKV9 or placebo under fasted conditions. AKV9 or placebo will be given as an oral suspension.
Part A will include six cohorts of healthy adults aged 18-55 years and one cohort of healthy older adults aged 56-75 years. For each dose level, 8 participants will be randomized 3:1 to AKV9 or placebo (6 participants AKV9: 2 participants placebo).
• Cohort 1: 75 mg AKV9 (6 participants) or placebo (2 participants)
• Cohort 2: 150 mg AKV9 (6 participants) or placebo (2 participants)
• Cohort 3: 300 mg AKV9 (6 participants) or placebo (2 participants)
• Cohort 4: 600 mg AKV9 (6 participants) or placebo (2 participants)
• Cohort 5: 1200 mg AKV9 (6 participants) or placebo (2 participants)
• Cohort 6: 2000 mg AKV9 (6 participants) or placebo (2 participants)
• Cohort 7: dose to be determined based on Safety Review Committee (SRC) review of available safety and PK data from previous cohorts. The possible dose range will be between 75-2000 mg.

In Part B a total of approximately 16 healthy adult participants aged 18 to 55 years will be enrolled in a sequential fashion to 1 of 2 treatment cohorts to evaluate the effect of multiple-dose administration of AKV9 on safety and PK parameters. Each cohort will randomize 8 participants in a 3:1 ratio (6 AKV9: 2 placebo) to receive AKV9 or placebo orally under fasting conditions once daily (QD) for 10 days. The SRC will review all available safety and PK data from Part A (SAD) of the study to determine the dose levels for Part B (MAD) of the study. The possible dose range will be between 75-2000 mg. The dose increment may be 2-3 x.

The highest dose level tested in Part B will not exceed the highest dose level administered in Part A.
Participants will be dosed as in-patients and adherence will be monitored by site staff.
Intervention code [1] 335414 0
Treatment: Drugs
Description of the comparator or control
This study will involve the use of an oral Placebo. The placebo formulation will be orally administered in the same manner as the active formulation of AKV9 suspension. The placebo will consist of the suspending agent, Ora-Plus.

Part A will enroll approximately 56 participants to 1 of 7 cohorts in a sequential fashion with 8 participants enrolled per cohort. Cohorts 1 through 7 will be randomized 3:1 to receive a single dose of AKV9 or placebo. Cohort 7: dose to be determined by SRC (not to exceed the highest dose administered in Cohorts 1 – 6) of AKV9 (6 participants) or placebo (2 participants).

Part B will enroll approximately 16 participants aged 18 to 55 years to 1 of 2 cohorts in a sequential fashion with 8 participants enrolled per cohort. Cohorts 8 and 9 will be randomized 3:1 to receive AKV9 (6 participants) or placebo (2 participants) QD for 10 days.
Control group
Placebo

Outcomes
Primary outcome [1] 346988 0
To assess the safety and tolerability of single and multiple doses of AKV9 in healthy adult participants. Safety and tolerability will be assessed as a composite outcome.
Timepoint [1] 346988 0
AEs will be assessed at each visit and the severity of each AE and SAE will be assessed continuously as they are reported or observed and reviewed daily up until end of treatment (EOT) visit. Physical examinations will be assessed for Part A at screening, day -1. day 1, 2 and 7; Part B at screening, day -1, daily from day 2 to 10, day 12. Clinical laboratory testing will occur for Part A at screening, day 1, 2 and 7; Part B at screening, day 1, 2, 4, 7, 10, 11 and 12. Vital signs will be assessed for Part A at screening, day -1. day 1, 2 and 7; Part B at screening, day -1, daily from day 1 to day 12. ECG will be performed for Part A at screening, day -1. day 1, 2 and 7; Part B at screening, day -1, daily from day 1 to day 12.
Secondary outcome [1] 468492 0
To assess the pharmacokinetics of AKV9 in plasma. This outcome is assessed for both Part A and Part B.
Timepoint [1] 468492 0
Blood samples for Part A will be collected on day 1 (pre-dose, postdose at 0.25hr, 0.5hr, 0.75hr, 1hr, 1.5hr, 2hr, 3hr, 4hr, 5hr, 6hr, 8hr, 12hr, 18hr and 24hr). Blood samples for Part B will be collected on day 1 and day 10 (pre-dose, postdose at 0.25hr, 0.5hr, 0.75hr, 1hr, 1.5hr, 2hr, 3hr, 4hr, 5hr, 6hr, 8hr, 12hr, 18hr and 24hr), predose on Day 4 and day 7 and 48hrs postdose on Day 12.
Secondary outcome [2] 468493 0
To assess the pharmacokinetics of AKV9 in urine. This outcome is assessed for both Part A and Part B.
Timepoint [2] 468493 0
Urine samples for Part A will be collected during the time intervals -2 to 0 hrs predose on Day 1, postdose on Day 1: 0-4hrs, 4-8hrs and 8-24 hrs. Urine samples for Part B will be collected during the time intervals -2 to 0 hrs predose on Day 1 and Day 10, postdose on Day 1 and Day 10: 0-4hrs, 4-8hrs and 8-24 hrs.
Secondary outcome [3] 469086 0
To assess the distribution of AKV9 to cerebrospinal fluid following multiple oral doses of AKV9. This outcome is assessed for Part B.
Timepoint [3] 469086 0
Cerebrospinal fluid will be collected 2.5hrs postdose on Day 10.
Secondary outcome [4] 469087 0
To assess potential exploratory pharmacodynamic biomarkers following multiple oral doses of AKV9. This outcome is assessed for Part B.
Timepoint [4] 469087 0
Blood sample will be collected 2hrs predose on Day 1 and 2.5hrs postdose on Day 10.
Secondary outcome [5] 469088 0
To assess the palatability of oral suspension AKV9 formulation. This outcome is assessed for both Part A and Part B.
Timepoint [5] 469088 0
The questionnaire will be completed for Part A 15 minutes after dosing on Day 1. The questionnaire will be completed for Part B 15 minutes after dosing on Day 1 and Day 10.

Eligibility
Key inclusion criteria
1. Voluntarily consents to participate in this study and provides written informed consent prior to the start of any study-specific procedures.
2. Male or female between 18 and 55 years of age (inclusive) at Screening. Note: Cohort 7 of Part A (SAD) must be between 56 and 75 years of age (inclusive).
3. Has a body mass index (BMI) between 18 and 30 kg/m2 (inclusive) and weighs a minimum of 50 kg at Screening.
4. Female participants must agree to use a highly effective, medically accepted, contraceptive method with a failure rate <1% (e.g., established combined [estrogen and progestogen containing] or established progestogen only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, vasectomized partner, sexual abstinence) from Screening until 30 days after last dose of study medication if of childbearing potential OR must be of nonchildbearing potential (defined as surgically sterile [i.e., had a bilateral tubal ligation or salpingectomy, hysterectomy, or bilateral oophorectomy at least 6 months prior to the first dose of study medication] or postmenopausal for at least 1 year prior to the first dose of study medication with an FSH level of greater than or equal to 40 IU/L [if not using hormonal contraception or HRT]; in the absence of 12 months or more of amenorrhea, confirmation with 2 FSH measurements in the postmenopausal range is required). They must also agree not to donate eggs from Screening until 30 days after the last dose of study medication.
5. Male participants with sexual partners of childbearing potential must be surgically sterile OR must remain abstinent (if this is their preferred and usual lifestyle) OR must have a partner who uses a highly effective form of birth control (e.g., combined [estrogen and progestogen containing] or progestogen only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, sexual abstinence) and must agree to use contraception comprising a condom with intravaginal spermicide from Screening to 90 days following the last study medication administration. All male participants must agree not to donate sperm during the same period.
6. Is willing and able to comply with all the study requirements.
7. Has vital signs (measured supine after a minimum 3-minute rest) at Screening and on Day -1 within the following ranges: heart rate: 40 to 100 beats per minute; systolic blood pressure (BP): 90 to 145 mmHg; diastolic BP: 50 to 95 mmHg. Out-of-range vital signs may be repeated once per timepoint.
8. In the opinion of the PI/delegate, the participant is able to understand and comply with all protocol requirements.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Healthy volunteers
Yes
Key exclusion criteria
1. History or presence of clinically significant (as judged by the PI/delegate) cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the PI/delegate, would jeopardize the safety of the participant or the validity of the study results.
2. A clinically significant abnormal finding (as judged by the PI/delegate) on the physical exam, medical history, ECG, or clinical laboratory results. Laboratory parameters falling outside the specified eligibility ranges may be repeated within the screening window to rule out laboratory error or transient fluctuations. If the repeat value falls within the acceptable range, the participant may be enrolled, at PI/delegate discretion. Any laboratory abnormality at Screening or Day -1 that, in the opinion of the PI/delegate, is not clinically significant and does not pose a safety risk to the participant may be permitted upon mutual agreement with the Medical Monitor.
3. A documented history or clinical suspicion of Gilbert’s Syndrome. Mildly elevated bilirubin with completely normal conjugated bilirubin suggests Gilbert’s Syndrome.
4. For Part B (MAD) participants: Any suicidal ideation in the past 6 months, as indicated by a “yes” answer to questions 4 or 5 in the C-SSRS Baseline/Screening Version, (i.e. active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent) or any lifetime history of suicidal behavior, as indicated by any “yes” answer in the Suicidal Behavior section of the C-SSRS Baseline/Screening Version.
5. History or presence of allergic or adverse response to AKV9, or allergy to any of the components of the study medication.
6. Significant changes (as assessed by the PI/delegate) in diet/eating habits (quantity or type of foods) during the 4 weeks preceding the first dose of study medication.
7. Has participated in another clinical trial within 30 days prior to the first dose of study medication in this trial, or current participation in another clinical trial at the time of Screening.
8. Use of any over-the-counter medication (including nutritional or dietary supplements, herbal preparations, or vitamins) within 7 days prior to the first dose of study medication until the end-of-study visit without evaluation and approval by the PI/delegate.
9. Use of any prescription medication, except hormonal contraceptive or hormonal replacement therapy, from 14 days prior to the first dose of study medication until the end-of-study visit without evaluation and approval by the PI/delegate.
10. Has been treated with any known drugs that are moderate or strong inhibitors/inducers of cytochrome P450 enzymes (e.g., barbiturates, phenothiazines, cimetidine, carbamazepine) within 30 days prior to the first dose of study medication, and that, in the PI/delegate’s judgment, may impact participant safety or the validity of the study results.
11. Blood, plasma or platelet donation within 30 days prior to the first dose of study medication until the end-of-study visit. It is recommended that blood/plasma/platelet donations not be made for at least 30 days after the end-of-study visit.
12. Participant smokes more than 5 cigarettes or equivalent nicotine-containing products per week, and/or the participant is unwilling to abstain from smoking or the use of nicotine-containing products for 72 hours prior to check-in on Day -1 and throughout the confinement period at the study site. (Note: 1 average cigar = approximately 5 average cigarettes; 1 average pipe session = approximately 5 average cigarettes; 1 average nicotine liquid vape session = 1 average e-cigarette = 1 average cigarette).
13. Engagement in strenuous exercise from 48 hours prior to the first dose of study medication until after the Day 7 visit (Part A) or the Day 15 visit (Part B).
14. Consumption of beverages or foods that contain alcohol, grapefruit, poppy seeds, kale, broccoli, Brussels sprouts, pomegranate, star fruit, char-grilled meat, or caffeine/xanthine from 48 hours prior to the first dose of study medication until after the Day 7 visit (Part A) or the Day 15 visit (Part B). Participants will be instructed not to consume any of the above products; however, allowance for an isolated single incidental consumption may be evaluated and approved by the PI/delegate based on the potential for interaction with the study medication.
15. Has any prior history of substance abuse or treatment (including alcohol) as judged by the PI/delegate.
16. Is a female with a positive pregnancy test result, is pregnant, or is lactating.
17. Has a positive urine screen for drugs of abuse (amphetamine, barbiturates, benzodiazepines, cocaine, THC/cannabinoids, methadone, methamphetamine, opiates, phencyclidine, tricyclic antidepressants), a positive alcohol breath test, or a positive cotinine test on Day -1.
18. Has a positive hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) at Screening, or has been previously treated for hepatitis B, hepatitis C, or HIV infection.
19. Any other medical condition or social circumstance, which in the opinion of the PI/delegate would impede compliance with or hinder completion of the study.

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)
Participants will be assigned a unique randomization identification number prior to the first dosing, and will receive AKV9 or placebo, according to a randomization schedule. An authorised, trained staff member from the site pharmacy will dispense the study drug according to pre-defined drug dispensing requirements. AKV9 or placebo will be dispensed according to the assigned randomisation number.
Code break envelopes will be produced by the statistician and stored securely by authorised, trained site pharmacy staff.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation. That will enable exact allocations for each cohort including sentinel cohorts.
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
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
10/11/2026
Actual
Date of last participant enrolment
Anticipated
11/06/2027
Actual
Date of last data collection
Anticipated
10/07/2027
Actual
Sample size
Target
72
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 323093 0
Commercial sector/Industry
Name [1] 323093 0
Akava Therapeutics Australia Pty Ltd
Country [1] 323093 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Akava Therapeutics Australia Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 326046 0
Commercial sector/Industry
Name [1] 326046 0
Avance Clinical Pty Ltd
Address [1] 326046 0
Country [1] 326046 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 321494 0
Bellberry Human Research Ethics Committee H
Ethics committee address [1] 321494 0
Ethics committee country [1] 321494 0
Australia
Date submitted for ethics approval [1] 321494 0
23/09/2026
Approval date [1] 321494 0
03/11/2026
Ethics approval number [1] 321494 0

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

Contacts
Principal investigator
Name 153894 0
Dr Michele De Sciscio
Address 153894 0
Ground Floor, 21-24 North Terrace, Adelaide, South Australia, 5000
Country 153894 0
Australia
Phone 153894 0
+61 422 447 902
Fax 153894 0
Email 153894 0
[email protected]
Contact person for public queries
Name 153895 0
Kenneth Kashkin
Address 153895 0
Level 2, 169 Pirie Street, Adelaide, South Australia, 5000
Country 153895 0
Australia
Phone 153895 0
+61872230122
Fax 153895 0
Email 153895 0
[email protected]
Contact person for scientific queries
Name 153896 0
Kenneth Kashkin
Address 153896 0
Level 2, 169 Pirie Street, Adelaide, South Australia, 5000
Country 153896 0
Australia
Phone 153896 0
+61872230122
Fax 153896 0
Email 153896 0
[email protected]

Data sharing statement
Will the study consider sharing 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.