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Trial registered on ANZCTR


Registration number
ACTRN12625000334404
Ethics application status
Approved
Date submitted
21/02/2025
Date registered
17/04/2025
Date last updated
17/04/2025
Date data sharing statement initially provided
17/04/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomized, Double Blind, Single-Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetic Profile of EIK1005 in Healthy Participants.
Scientific title
Healthy Participant Study to Assess Safety, Tolerability and Pharmacokinetic Profile of EIK1005, a Werner helicase inhibitor.
Secondary ID [1] 310843 0
EIK 1005-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
MSI-H Solid Tumors 336744 0
Condition category
Condition code
Cancer 332800 332800 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
EIK1005 is a potent and selective inhibitor of the Werner helicase (WRN), which has been identified as a synthetic lethal target in microsatellite instability high (MSI-H) cells. MSI-H is a marker of cancer cells with defective mismatch repair .WRN inhibition (WRNi) acts on MSI-H cells, and thus WRNi is not expected to have an effect on healthy tissue.
EIK1005 is noncytotoxic and is being considered as a potential targeted therapy in patients with MSI-H or dMMR solid tumors. EIK1005 or placebo will be administered orally. For participants who are enrolled in Period 1 (fasted conditions) or Period 2 (fed conditions), they will receive one dose of EIK1005 or placebo; for participants who are enrolled in both Period 1 and Period 2, they will receive two doses of EIK1005 or placebo.
EIK1005 will be administered via oral tablet. Six dose levels will be assessed in Period 1 of the study: 50 mg, 100 mg, 200 mg, 400 mg, 800 mg and 1000 mg. Dose for Period 2 will be determine after evaluation of Period 1 data.
The study drug administration will be performed in-house under the supervision of the study team to ensure 100% adherence to the intervention.
For the fasted condition, participants will fast at least 10 hours prior to receiving a single dose of EIK1005. For the fed condition, participants will receive a meal in which greater than or equal to 50% of calories are from fat with total calories ranging from 800 to 1000. The meal will accommodate dietary needs including but not limited to vegan, vegetarian, Halal, or Kosher. Participants will then remain in the clinic for 3 days and will return on Day 8 for a follow-up visit. Medical assessments including blood draws will be performed during this time.
If a Period 1 participant from the selected dose cohort is not eligible or is unwilling to participant Period 2 (the food effect cohort), a new participant will be enrolled as a replacement and receive the same treatment assignment as the replacing participant. Therefore, there might be a participant or some participants who will be enrolled only into Period 2.
Intervention code [1] 330278 0
Treatment: Drugs
Comparator / control treatment
Placebo to match EIK1005
The placebo which is a tablet contains microcrystalline cellulose, colloidal silica dioxide, croscarmellose sodium, magnesium stearate and Opadry (R) 85F18422 white
Control group
Placebo

Outcomes
Primary outcome [1] 340323 0
To evaluate the safety and tolerability of single ascending doses of EIK1005 in healthy participants. There is no composite primary outcome as Adverse Events are the sole primary outcome.
Timepoint [1] 340323 0
All AEs will be collected from the signing of the ICF at screening until the follow-up phone call on Day 30 post-dose. Adverse Events will be assessed from the time of Screening, daily from Day -1 pre-dose to Day 4 post-dose while in-house, on Day 8 post-dose at the safety follow-up visit, and on Day 30 post-dose at the safety follow-up phone call and AEs will be reported by the participants as they occur and be assessed as an ongoing basis in between the visits. Vital signs (blood pressure assessed using digital sphygmomanometer, heart rate and respiratory rate assessed using pulse oximeter, and temperature assessed using digital thermometer) will be assessed from Screening, Day -1 pre-dose Day 1, 1, 2, 3, 4, 6, 8, 10, 12, 22 hours (hrs) post-dose, Day -2, 24 hrs post-dose, Day-3, 48 hrs post-dose, Day-4, 72 hrs post-dose and Day-8 (Safety follow-up visit). ECG's will be conducted in triplicate at Screening, Day -1, pre-dose Day 1, 2, 4, 6, 8, and 10 hrs post-dose, Day-2, 24 hrs post-dose, Day 3 post-dose, and Day 4 post-dose. Clinical laboratory blood and urine samples will be collected at Screening, Day -1, Day-2, 3 (clinical laboratory blood only), Day 4 and Day 8 (safety follow-up visit).
Secondary outcome [1] 444181 0
To characterize the PK of EIK1005 in healthy participants.
Timepoint [1] 444181 0
PK assessment will be performed starting at pre-dose on Day 1 and continue until Day 8 For assessment of plasma PK, blood samples will be collected pre-dose, at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 20, 22, 24, 48, 72 hours post-dose and on the Day 8 visit.
Secondary outcome [2] 444182 0
To determine the effect of food on the PK of EIK1005 in healthy participants.
Timepoint [2] 444182 0
PK assessments will be performed starting from pre-dose on Day 1 to Day 8. For assessment of plasma PK, blood samples will be collected pre-dose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 20, 22, 24, 48, 72 hours post-dose and on the Day 8 visit.

Eligibility
Key inclusion criteria
1. Woman of non-childbearing potential (WONCBP) or a man who is at least 18 years at the time of signing the ICF.
2. Healthy as determined by the Principal Investigator with no clinically significant abnormalities and no active clinically significant condition or disease.
3. Total body mass index (BMI) between 18 kg/m2 and 32 kg/m2 (inclusive).
4. Adequate organ and marrow function.
5. Male participants who are sexually active with women of childbearing potential (WOCBP) must agree to use an approved and highly effective contraceptive method throughout the study Visit 1 to 90 days after the last dose of study drug. Male participants cannot donate sperm for 90 days after the last dose of study drug.
6. Willing and able to provide written, informed consent for the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Participant has a history or presence of clinically relevant medical condition(s) or disease(s).
2. Participant has a history or presence of any malignancy in the last 5 years except surgically cured skin cancers.
3. Participant is known to have Lynch syndrome, Werner Syndrome (progeria), or has a first degree relative with Werner Syndrome (progeria).
4. Participant has a history of relevant drug hypersensitivity, to the active drug substance and/or formulation ingredients.
5. Participant uses any prescribed medication or over-the-counter drug within 7 Days or 5 times the half-life of the respective drug, whichever is longer prior to the first administration of EIK1005. The Principal Investigator may determine exceptions in consultation with the Sponsor.
6. There is a mean resting QTcF > 450 ms in men and QTcF > 460 ms in women obtained from triplicate ECGs.
7. Participant who has been diagnosed with hepatitis B virus (HBV) infection or has an active hepatitis C virus (HCV) infection.
8. Participant with positive human immunodeficiency virus (HIV) serology or known HIV diagnosis.
9. Participant has received a live-virus vaccination within 90 days of the start of study drug.
10. Participant had major surgery (< 3 months prior to receiving EIK1005 or placebo).
11. Participant has donated or lost >= to 450 mL of blood within 90 days prior to Screening.
12. Participant is unable or unwilling to swallow pills.

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)
Allocation involved contacting the holder of the allocation schedule who was "off-site" or at central administration site.
All participants who pass the screening will be assigned to a study treatment using a predefined allocation schedule. Treatment allocation is carried out by an unblinded pharmacist, who holds the allocation schedule and is based at a different location from the Investigator.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomization uses a randomization schedule created by computer software.
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
Other
Other design features
At each dose level, 6 participants will receive EIK1005 and 2 participants will receive placebo. under fasted conditions (Period 1). Period 1 will have 6 dose levels with more dose levels to be added as applicable. The participants from one dose level in Period 1 will receive EIK1005 or placebo under fed conditions (Period 2), according to their original randomized treatment group.
For participants who are enrolled in Part 1 or Part 2, one dose of EIK1005 or placebo is planned
For participants who are enrolled in both Parts 1 and 2, two doses of EIK1005 or placebo are planned with a washout period of approximately 4 to 6 weeks.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Safety and tolerability will be assessed by clinical review of all relevant parameters, including AEs and laboratory values.
Plasma concentrations of EIK1005 will be analyzed by noncompartmental methods to determine AUCinf, AUClast, Cmax, Tmax, and T1/2.
A mixed effects model will be used to evaluate the effect of a high-fat, high caloric meal on the PK of EIK1005.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
22/04/2025
Actual
Date of last participant enrolment
Anticipated
21/08/2025
Actual
Date of last data collection
Anticipated
20/09/2025
Actual
Sample size
Target
48
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 27485 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 43594 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 315091 0
Commercial sector/Industry
Name [1] 315091 0
EIKON Therapeutics, Inc.
Country [1] 315091 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
EIKON Therapeutics, Inc.
Address
Country
United States of America
Secondary sponsor category [1] 320849 0
None
Name [1] 320849 0
Address [1] 320849 0
Country [1] 320849 0
Other collaborator category [1] 283435 0
Commercial sector/Industry
Name [1] 283435 0
KlinEra Global Services Pty Ltd
Address [1] 283435 0
Country [1] 283435 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314036 0
Bellberry Human Research Ethics Committee G
Ethics committee address [1] 314036 0
Ethics committee country [1] 314036 0
Australia
Date submitted for ethics approval [1] 314036 0
05/02/2025
Approval date [1] 314036 0
18/03/2025
Ethics approval number [1] 314036 0

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

Contacts
Principal investigator
Name 130198 0
Dr Philip Ryan
Address 130198 0
Nucleus Network, 549 St Kilda Road, Level 3, Melbourne, Victoria 3004, Australia
Country 130198 0
Australia
Phone 130198 0
+61 438 009 787
Fax 130198 0
Email 130198 0
[email protected]
Contact person for public queries
Name 130199 0
Aishwarya Movva
Address 130199 0
Associate Director, Clinical Study Management, Eikon Therapeutics Inc, 230 Harriet Tubman Road, Millbrae, CA 94030
Country 130199 0
United States of America
Phone 130199 0
+13417770566
Fax 130199 0
Email 130199 0
[email protected]
Contact person for scientific queries
Name 130200 0
Wen Hong Lin, MD, MSc
Address 130200 0
Eikon Therapeutics Inc, Executive Director, Clinical Research, Oncology, 3 2nd Street, 4th Floor, Jersey City, NJ 07302
Country 130200 0
United States of America
Phone 130200 0
+12155272383
Fax 130200 0
Email 130200 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.