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Trial registered on ANZCTR


Registration number
ACTRN12622001571763
Ethics application status
Approved
Date submitted
9/12/2022
Date registered
20/12/2022
Date last updated
24/04/2023
Date data sharing statement initially provided
20/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 Single Dose Study in Healthy Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of EARLI-001
Scientific title
A Phase 1 Single Dose Study in Healthy Subjects to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of EARLI-001
Secondary ID [1] 308583 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record
ACTRN12620001178932
In this trial, cancer patients in Australia were dosed with the same doses (0.003mg/kg and 0.013mg/kg) of EARLI-001 that healthy volunteers will be receiving in this study.

Health condition
Health condition(s) or problem(s) studied:
Cancer Diagnosis 328443 0
Condition category
Condition code
Cancer 325474 325474 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
EARLI-001 is a recombinant DNA nanoplasmid that uses the human survivin promoter to drive cancer-activated expression of secreted embryonic alkaline phosphatase (SEAP) to act as a biomarker for the detection of cancer. EARLI-001 is given as a single intravenous dose.
This is a phase 1 open-label study to assess the safety, tolerability, pharmacodynamics and pharmacokinetics of two single ascending doses of EARLI-001 in healthy participants at a single site in Australia. Up to 10 participants will receive the study drug at one of two dose levels (0.003mg/kg or 0.013mg/kg) via an intravenous infusion at a rate of ~1ml/minute. The following is how the participants will be dosed:
Cohort 1 (first 5 participants): 0.003mg/kg
Cohort 2 (last 5 participants): 0.013mg/kg
Participants will stay confined in the clinical unit to complete safety assessments for 24 hours post-dosing and will then return to the clinical site on Days 3,5,7, 14 and 28 days post-dose for follow-up assessments. The study drug will be administered to participants by trained nurses in adherence to the strict study protocol.
Intervention code [1] 325026 0
Early detection / Screening
Intervention code [2] 325027 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 333326 0
To evaluate the safety and tolerability of EARLI-001 in healthy volunteers.
Safety assessments include the monitoring of the incidence and severity of adverse events. The participant will report these to site staff. Open-ended and non-leading verbal questioning of the participant will be used to enquire about AE occurrences.. The same doses of EARLI-001 used in this study (0.003mg/kg and 0.013mg/kg) have been trialled in cancer patients. Some of the cancer patients who were dosed with EARLI-001 experienced a mild to moderate post-infusion reaction (fever and or chills) after dosing. These symptoms resolved after the patients were treated with ibuprofen.
Clinically significant changes from baseline will also be monitored in:
- laboratory evaluations (haematology, chemistry, coagulation and urinalysis)
- electrocardiograms (ECG): using a 12 lead ECG machine
- vital signs including; oral temperature, pulse rate, respiratory rate and blood pressure. Temperature, blood pressure and pulse rate are assessed using a vitals machine. Respiratory rate is assessed using a 30-second manual count.
- physical examinations include examinations of the following; general appearance, head, ears, eyes, nose, throat, neck, skin, cardiovascular system, respiratory system, gastrointestinal system, musculoskeletal system, lymph nodes and nervous system. This will be performed by a study-delegated registered physician.
Timepoint [1] 333326 0
Dosing will occur on Day 1.
Adverse events will be monitored throughout the study. This will be during confinement on Days 1 and 2 and during the follow-up visits on Days 3,5,7,14 and 28.
Laboratory evaluations will occur at participant check in (Day -1) and on Days 2,3,5,7,14 and 28 post-dose.
ECGs will be performed at check-in and on days 1,2,5,7,14 and 28.
Vital Signs will be monitored at check-in and on days 1,2,3,5,7,14 and 28.
Physical exams will be performed at check-in and on Days 2,5,7,14 and 28.
Primary outcome [2] 333328 0
To determine the pharmacokinetic profile of EARLI-001 following single-dose administration.
Pharmacokinetic parameters of EARLI-001 include maximal concentration, time for maximal concentration, area under the concentration-time curve, half life, elimination rate constant and total body clearance.

Timepoint [2] 333328 0
PK blood samples will be collected from the participants prior to dosing and at 0.5,1,2,4,6,8,10,24 and 48 post-dose.
Primary outcome [3] 333329 0
To measure the pharmacodynamic effect of EARLI-001 through comparison of change from baseline in the measured secreted embryonic alkaline phosphatase (SEAP), a biomarker produced from EARLI-001. SEAP levels will be assayed at the EARLI laboratory.
Timepoint [3] 333329 0
PD blood samples will be collected from the participants prior to dosing and at 1,2,4,6,8,10,24 and 48 hours post-dose.
Secondary outcome [1] 416661 0
To measure the effect of EARLI-001 on cytokine levels .The following cytokines are likely to be measured using a validated commercially available multiplex assay at the Earli laboratories: Th1/Th2: GM-CSF, IFN gamma, IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-12p70, IL-13, IL-18, TNF alpha, Th9/Th17/Th22/Treg: IL-9, IL-10, IL-17A (CTLA-8), IL-21, IL-22, IL-23, IL-27
Inflammatory cytokines: IFN alpha, IL-1 alpha, IL-1RA, IL-7, IL-15, IL-31, TNF beta
Chemokines: Eotaxin (CCL11), GRO alpha (CXCL1), IP-10 (CXCL10), MCP-1 (CCL2), MIP-1 alpha (CCL3), MIP-1 beta (CCL4), RANTES (CCL5), SDF-1 alpha
Timepoint [1] 416661 0
Samples will be drawn to measure cytokine levels prior to dosing and at 0.5,1,2,4,6,8,10,24 and 48 hours post-dose.

Eligibility
Key inclusion criteria
1. Be willing and able to sign the informed consent and comply with study procedures.
2. Be between the ages of 18 and 55, inclusive
3. Be male or female and meet the following conditions:
- Female participants must not have childbearing potential, defined as surgically sterile (hysterectomy, bilateral salpingectomy, tubal ligation or bilateral oophorectomy - verbal confirmation through medical history review acceptable) or postmenopausal (no menses for 12 months and confirmed by FSH level greater than or equal to 40 mlU/mL), or, if of childbearing potential be non-pregnant or lactating and agree to use highly effective contraception from screening through Day 30.
- Male participants, if not surgically sterilized, and if engaging in sexual intercourse with a female partner of childbearing potential, must be willing to use highly effective contraception from screening through 90 days post-dose and agree not to donate semen during this same period.
- Participants who abstain from intercourse as their usual and preferred lifestyle or participants with a same-sex partner are not required to use contraception as described above. They are required to maintain abstinence from screening through Day 30.
4. Be considered healthy by the Investigator, based on a detailed medical history, full physical examination, clinical laboratory tests, 12-lead ECG and vital signs
5. Have a BMI between 18-32 Kg/m2
6. Weigh more than 50 kg.
7. Be a nonsmoker, defined as not having smoked, vaped or used any form of tobacco for more than 6 months before screening. Subjects who smoke occasionally (no more than 2 cigarettes per week) are allowed to participate provided their cotinine test is negative at screening and baseline and they abstain from smoking during the study.
8. Be willing to stop all prescription or over-the-counter medications they are currently taking from 7 days prior to admission to Day 7 of the study..
9. Be willing to abide by the study-specific restrictions on diet and exercise as described in the informed consent.
10. Not have participated in a clinical trial within the last 30 days prior to screening, or 5 half-lives, whichever is longer
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. A prior history of cancer.
2. A positive blood screen for human immunodeficiency virus antibodies (HIV), hepatitis B surface or core antigen (HBsAg/HBcAg), or hepatitis C antigen
3. A history of clinically significant symptomatic hypotension.
4. Abnormal systolic or diastolic BP or heart rate outside of the Linear acceptable limits at Screening or Day -1.
5. Congenital long QT syndrome or QTcF > 450 ms (males) or >470 ms (females) by history or at Screening ECG.
6. WBC, neutrophils, hemoglobin and platelet counts out of the local laboratory range of normal.
7. AST, ALT or bilirubin value > upper limit of normal (ULN) at screening. Repeat testing one time is acceptable.
8. Serum creatinine > ULN at screening.
9. A hospital admission or major surgery within 30 days prior to screening
10. A pre-planned hospital admission or surgery scheduled within 30 days after dosing.
11.. A history of prescription drug abuse or illicit drug use within 6 months prior to screening
12. A history of alcohol abuse within 6 months prior to screening as determined by the PI
13.A positive screen for alcohol or drugs of abuse including cotinine
14. Donated more than one unit of blood or blood products during the 3 months prior to screening or receipt of a blood transfusion within one year prior to screening.
15. Any other co-morbidity or habit that the Investigator believes will interfere with their ability to comply with and complete the study.

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



Intervention assignment
Other
Other design features
All participants in this study will receive the study drug at one of two dose levels. Participants will be allocated to cohorts in the following sequential order:
Cohort 1 (first 5 participants): 0.003mg/kg of EARLI-001
Cohort 2 (last 5 participants): 0.013mg/kg of EARLI-001
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
This is an open-label, early development study, and therefore no statistical considerations were involved in the sample size determination. It is expected that the sample size of 10 subjects in 2 cohorts should be adequate for the evaluation of safety, tolerability and pharmacokinetics in this single-dose study.

Statistical Analysis Plan:
Adverse events: will be summarized by the Medical Dictionary for Regulatory Activities (MedDRA) system organ class and preferred term. All subjects in the safety analysis set will be included in the summaries. Events will be summarized on the basis of the date of onset for the event. No statistical testing will be performed. All AEs collected during the study will be presented in a listing.
Clinical Laboratory data Summaries of clinical laboratory results and change from baseline will be performed using descriptive statistics by scheduled visit. All subjects in the safety population will be included in these summaries. No statistical testing will be performed.
Other safety evaluations: Individual data for physical examination findings, prior and concomitant medications and medical history will be provided. Twelve-lead ECGs and vital signs measurements will be listed by subject and summarized by the incidence of events/abnormalities or descriptive statistics as appropriate. No statistical testing will be performed.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
New data did not support continuing this trial.
Date of first participant enrolment
Anticipated
3/03/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 23695 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 39130 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 312833 0
Commercial sector/Industry
Name [1] 312833 0
Earli Pty. Ltd.
Country [1] 312833 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Earli Pty. Ltd.
Address
c/o William Buck
Level 20
181 William Street
Melbourne, VIC 3000
Country
Australia
Secondary sponsor category [1] 314474 0
None
Name [1] 314474 0
Address [1] 314474 0
Country [1] 314474 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312111 0
Bellberry Ltd..
Ethics committee address [1] 312111 0
23 Glen Osmond Rd, Eastwood, 5063, SA
Ethics committee country [1] 312111 0
Australia
Date submitted for ethics approval [1] 312111 0
07/12/2022
Approval date [1] 312111 0
02/02/2022
Ethics approval number [1] 312111 0
Bellberry Application Number: 2022-12-1347

Summary
Brief summary
The purpose of this study is to determine the assess the safety, tolerability, pharmacodynamics and pharmacokinetics of EARLI-001, a product developed to asses with the detection of cancer.

Who is it for?
You may be eligible for this study if you are a healthy adult under the age of 55.

Study details

Participants will receive the study drug via an infusion in the vein and be required to stay at the testing clinic for 24 hours for observation. They will then be required to attend follow-up assessments on days 3,5,7, 14 and 28.

As part of this study, we will be collecting blood samples for both safety and research purposes. During the study, the estimated total blood volume to be collected will be approximately 140 mL (approximately 0.6 cups or 7 tablespoons). As a reference, a standard blood donation is 470 mL in any 12-week period. At follow-up visits, participants will also undergo physical examinations, vital sign assessments (blood pressure, pulse rate, breathing rate and temperature) and electrocardiograms for the assessment of safety.

It is hoped that this research will help determine if this product is safe for use, to then be used further in future studies to determine whether this product can be used to assist cancer detection.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 123514 0
Dr Andrew Redfern
Address 123514 0
Linear Clinical Research
1 Hospital Avenue, B-Block, 1st Floor,
Nedlands WA 6009
Country 123514 0
Australia
Phone 123514 0
+61 0433078719
Fax 123514 0
Email 123514 0
[email protected]
Contact person for public queries
Name 123515 0
Nicola Norton
Address 123515 0
Linear Clinical Research
1 Hospital Avenue, B-Block, 1st Floor,
Nedlands WA 6009
Country 123515 0
Australia
Phone 123515 0
+61 8 6382 5100
Fax 123515 0
Email 123515 0
[email protected]
Contact person for scientific queries
Name 123516 0
Andrew Redfern
Address 123516 0
Linear Clinical Research
1 Hospital Avenue, B-Block, 1st Floor,
Nedlands WA 6009
Country 123516 0
Australia
Phone 123516 0
+61 0433078719
Fax 123516 0
Email 123516 0
[email protected]

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.