ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12623000440628

Ethics application status

Approved

Date submitted

20/03/2023

Date registered

1/05/2023

Date last updated

28/04/2024

Date data sharing statement initially provided

1/05/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

A Study of ELVN-002 in Healthy Adult Volunteers: Part A

Scientific title

A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ELVN-002 in Healthy Adult Volunteers: Part A: Randomised, Double-blind, Placebo-controlled, Single Ascending Dose Study

Secondary ID [1]

ELVN-002-002

Universal Trial Number (UTN)

Trial acronym

Linked study record

The study consist of three parts. Part A, Part B and Part C.
- Part B of the study is registered ACTRN12623000431628

Health condition

Health condition(s) or problem(s) studied:

Non-small Cell lung cancer

Condition category

Condition code

Cancer

Lung - Non small cell

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Investigational Product (IP): ELVN-002
Dosage Form: Capsule
Mode of Administration: Oral
Part A (SAD):
In Part A (SAD), eligible participants will be administered a single dose of ELVN-002 or placebo at a ratio of 3:1 in each cohort, with 6 participants receiving ELVN-002 and 2 receiving placebo. Six cohorts will be included in Part A.
Cohort A1: 22.5 mg of ELVN-002 or placebo single oral administration on Day 1
Cohort A2: 45 mg of ELVN-002 or placebo single oral administration on Day 1
Cohort A3: 90 mg of ELVN-002 or placebo single oral administration on Day 1
Cohort A4: 180 mg of ELVN-002 or placebo single oral administration on Day 1
Cohort A5: 360 mg of ELVN-002 or placebo single oral administration on Day 1
Cohort A6: 540 mg of ELVN-002 or placebo single oral administration on Day 1
One of the SAD cohorts (Cohort 1 to Cohort 5) will be considered as Food Effect Cohort where participants will receive second dose of assigned ELVN-002 on Day 10 (+/-1)
On Day -1 in the Part A (SAD) cohorts, participants will fast for at least 10 hours before receiving ELVN-002 or placebo. Participants will continue fasting for at least 4 hours after dosing (water intake will be permitted 1 hour after dosing) for all cohorts.
On Day 9, participants in the FE Cohort will fast for at least 10 hours before dosing. On dosing day (Day 10 ± 1), participants will consume a standardised (high-fat, high-calorie) breakfast, as recommended by the U.S. Food and Drug Administration (FDA 2022), within 30 minutes and then take ELVN-002 or placebo orally for all cohorts.
A high-fat (approximately 50 percent of total caloric content of the meal) and high-calorie (approximately 800 to 1000 calories) meal is recommended as a test meal for food-effect studies.
This test meal should derive approximately 150, 250, and 500-600 calories from protein, carbohydrate, and fat, respectively.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

ELVN-002 Placebo made up of Microcrystalline cellulose. The drug formulation for Placebo is Capsule.

Control group

Placebo

Outcomes

Primary outcome [1]

Part A: Plasma PK profile of ELVN-002 in fasted healthy volunteers
Blood sample will be collected for Pharmacokinetic assessment.
Pharmacokinetic (PK) Parameters:
- Maximum concentration (Cmax)
- Time to maximum concentration (Tmax)
- Area under the curve (AUC) from time 0 to the last measurable concentration (AUC0-last)
- AUC from time 0 to infinity (AUC8)
- Half-life (t½)
- Apparent oral body clearance (CL/F)
- Apparent volume of distribution (Vz/F)

Timepoint [1]

Part A: PK blood samples will be collected pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 144 hours post-dose.

Primary outcome [2]

Part A: The safety and tolerability profile of ELVN-002 in fasted healthy volunteers.

- The incidence of adverse events (AEs) and serious adverse events (SAEs) will be coded using the most recent version of Medical Dictionary for Regulatory Activities (MedDRA)
- Vital signs (systolic and diastolic blood pressure assessed using a digital sphygmomanometer, heart rate assessed using a pulse oximeter, respiratory rate, and body temperature)
- Laboratory test results (including haematology, biochemistry, coagulation, urinalysis, and serology)
- Physical examination

Timepoint [2]

Adverse events (AEs) and serious adverse events (SAEs):
Part A (Excluding FE Cohort): Daily from Screening to Day 7 post-dose administration

Vital signs:
Part A (Excluding FE Cohort): Daily from Screening to Day 7 post-dose administration

Laboratory test:
Part A (Excluding FE Cohort): Daily from Screening, Day -1, Day 2, Day 4 and Day 7

Physical examination:
Part A (Excluding FE Cohort): Screening, Day -1, Day 2, 6, 7

Primary outcome [3]

Part A (Food Effect Cohort): Plasma PK profile of ELVN-002 in healthy volunteers
Blood sample will be collected for Pharmacokinetic assessment.
Pharmacokinetic (PK) Parameters:
- Maximum concentration (Cmax)
- Time to maximum concentration (Tmax)
- Area under the curve (AUC) from time 0 to the last measurable concentration (AUC0-last)
- AUC from time 0 to infinity (AUC8)
- Half-life (t½)
- Apparent oral body clearance (CL/F)
- Apparent volume of distribution (Vz/F)

Timepoint [3]

Part A (Food Effect Cohort): For fasting period, PK blood samples will be collected pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 144 hours post-dose (Day 1 to Day 6), and for fed period, PK blood samples will be collected pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours post-dose (Day 10 [± 1] to Day 12).

Secondary outcome [1]

Part A: Urine PK profile of ELVN-002 in healthy volunteers.
Urine sample will be collected for Pharmacokinetic assessment.
Pharmacokinetic Parameters:
- Cumulative amount of drug excreted in urine (Ae)
- Fraction of drug recovered in urine (Fe)
- Renal clearance (CLr).

Timepoint [1]

Part A: PK urine samples will be collected pre-dose and at 0 to 4 hours post-dose, 4 to 8 hours post-dose, 8 to 12 hours post-dose, 12 to 24 hours post-dose, and 24 to 48 hours post-dose

Secondary outcome [2]

Part A: Plasma PK profile of ELV-2228, a major metabolite of ELVN-002, in fasted healthy volunteers

Pharmacokinetic Parameters:
- Maximum concentration (Cmax)
- Time to maximum concentration (Tmax)
- Area under the curve (AUC) from time 0 to the last measurable concentration (AUC0-last)
- AUC from time 0 to infinity
- Half-time (t½)
- Metabolite-to-parent AUC and Cmax ratios

Timepoint [2]

Part A: PK blood samples will be collected pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, and 144 hours post-dose.

Secondary outcome [3]

Part A (Food Effect Cohort): The safety and tolerability profile of ELVN-002 in healthy volunteers.

- The incidence of adverse events (AEs) and serious adverse events (SAEs) will be coded using the most recent version of Medical Dictionary for Regulatory Activities (MedDRA)
- Vital signs (systolic and diastolic blood pressure assessed using a digital sphygmomanometer, heart rate assessed using a pulse oximeter, respiratory rate, and body temperature)
- Laboratory test results (including haematology, biochemistry, coagulation, urinalysis, and serology)
- Physical examination

Timepoint [3]

Adverse events (AEs) and serious adverse events (SAEs):
Part A (FE Cohort): Daily from Screening to Day 13 ± 1 post-dose administration

Vital signs:
Part A (FE Cohort): Daily from Screening to Day 13 ± 1 post-dose administration

Laboratory test:
Part A (FE Cohort): Daily from Screening, Day -1, Day 2, Day 4 to Day 9, Day 11 , Day 13 (+/-1)

Physical examination:
Part A (FE Cohort): Screening, Day -1, 2, 4, 7, 9, and 11; a symptom directed physical examination will be performed on Day 13 (±1).

Secondary outcome [4]

Part A (Food Effect Cohort): Plasma PK profile of ELV-2228, a major metabolite of ELVN-002, in healthy volunteers

Pharmacokinetic Parameters:
- Maximum concentration (Cmax)
- Time to maximum concentration (Tmax)
- Area under the curve (AUC) from time 0 to the last measurable concentration (AUC0-last)
- AUC from time 0 to infinity
- Half-time (t½)
- Metabolite-to-parent AUC and Cmax ratios

Timepoint [4]

Eligibility

Key inclusion criteria

1. Male or female, aged more than 18 to less than 60 years old (both inclusive at the time of informed consent).
2. In good general health, with no significant medical history, and no clinically significant abnormalities on physical examination at Screening and/or before the first administration of IP at the discretion of the PI or designee.
3. Body mass index (BMI) greater than 18 and less than 32.0 kg/m2 at Screening and weight more than 50 kg.
4. Non-smoker (has not used any tobacco products). A participant who smokes less than 2 cigarettes or equivalent (eg, cigars, vaping, nicotine patches) per week within 3 months prior to Screening can be included in the study if willing and able to stop smoking for the duration of the study, at the discretion of the PI or designee.
5. Clinical laboratory values at Screening (including haematology, biochemistry, coagulation, and urinalysis) within normal range as specified by the testing laboratory, unless deemed not clinically significant by the PI or designee.
6. Acceptable estimated glomerular filtration rate (eGFR) for the study using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation: greater than 89 mL/min/1.73 for participants 18 to 59 years old, or greater than 84 mL/min/1.73 for participants 60 years old).
7. Women of childbearing potential (WOCBP) must have a negative pregnancy test at Screening and Day -1 and be willing to have additional pregnancy tests as required throughout the study.
8. Female participants who meet 1 of the following criteria will be included.
a. Female participants must not be pregnant or lactating, and must use acceptable, highly effective double contraception from Screening until 90 days after the last study procedure is completed. Females with same-sex partners (abstinence from penile-vaginal intercourse) or who are abstinent from heterosexual intercourse are not required to use contraception when this is their preferred and usual lifestyle. Effective forms of contraception include:
• Simultaneous use of intrauterine device (IUD) (non-hormonal) and condom for the male partner.
• Simultaneous use of diaphragm or cervical cap and male condom for the male partner.
• Sterile male partner (vasectomized since at least 6 months prior to first IP administration).
• True abstinence, defined as no sexual intercourse (heterosexual couples). Periodic abstinence and withdrawal are not acceptable methods.
b. Women of non-childbearing potential (WONCBP), defined as postmenopausal for at least more than 12 months, confirmed by follicle stimulating hormone (FSH) levels greater than 40 IU/L, or judged by the Investigator.
9. Male participants must be surgically sterile (more than 90 days since vasectomy with no sperm on sperm analysis; verbal report allowed), or if engaged in sexual relations with a WOCBP, either his partner must be surgically sterile (eg, tubal occlusion, tubal ligation, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or an acceptable, highly effective contraceptive method must be used from Screening until 90 days after the last study procedure is completed. Effective forms of contraception are shown in Inclusion criterion 7.
Males with same-sex partners (abstinence from penile-vaginal intercourse) or are abstinent from heterosexual intercourse are not required to use contraception when this is their preferred and usual lifestyle. Males must not donate sperm from the first dose of IP until at least 90 days after the last dose of IP.
10. Able and willing to comply with the study procedure and the restriction specified in the protocol.
11. Able and willing to provide written informed consent after the nature of the study and the potential risk related to participating in the study have been explained and prior to the commencement of any study procedures.
12. Systolic blood pressure of 90 to 140 mmHg and diastolic blood pressure of 40 to 90 mmHg.
13. Resting heart rate of 40 to 100 beats per minute (bpm).

Minimum age

18 Years

Maximum age

60 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

1. Has participated in previous studies of ELVN-002.
2. Underlying physical or psychological medical condition that, in the opinion of the PI, could impact on the participant’s safety, participant involvement in the study, or data integrity.
3. History or surgical records of any clinically significant renal, cardiovascular, hepatic, hematopoietic, neurological, pulmonary, or gastrointestinal pathology, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of the IP, as determined by the PI or designee.
4. History of severe allergic or anaphylactic reactions, or sensitivity to ELVN-002, itraconazole, and phenytoin, or their constituents.
5. History of malignancy, except for non-melanoma skin cancer, excised more than 2 years ago and cervical intraepithelial neoplasia that has been successfully cured more than 5 years prior to Screening (a general practitioner [GP] letter or biopsy report for confirmation required).
6. History of symptomatic bacterial or viral infection within 2 weeks prior to Screening.
7. Abnormal ECG findings at Screening or Day -1 (eg, repeated demonstration of a QTc interval greater than 450 ms (male) or greater than 470 ms (female) corrected by Fridericia's formula [QTcF] or Bazett's formula [QTcB]) that are considered by the PI or designee to be clinically significant.
8. History of clinically significant arrhythmia, cardiac conditions, or risk factors for Torsades de Pointes (eg, heart failure, current hypokalaemia, and family history of long QT syndrome).
9. Clinically significant findings in transthoracic echocardiogram at Screening, including less than normal left ventricular ejection fraction (LVEF).
10. Blood donation or significant blood loss (greater than 500 mL) within 60 days prior to the first administration of IP.
11. Plasma donation within 30 days prior to the first administration of IP.
12. Poor pill swallowing ability.
13. Vaccination with a live vaccine within 1 month prior to the first administration of ELVN-002.
14. Participants who do not have suitable veins for multiple venepunctures/cannulations, as assessed by the Investigator at Screening.
15. Positive test for hepatitis C antibody (HCV), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or human immunodeficiency virus (HIV) antibody at Screening.
16. Known or suspected history of drug, alcohol, or other substrate abuse within 6 months prior to Screening (verbal confirmation is acceptable).
Regular alcohol consumption defined as greater than 21 units per week for males or greater than 14 units per week for females (where 1 unit equal to 285 mL of beer, 30 mL of spirit, or a 150 mL glass of wine).
17. Positive drugs of abuse screening panel (urine test including but not limited to amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, ecstasy (methylenedioxymethamphetamine [MDMA]), methadone, methamphetamines, phencyclidine, opiates, and tetrahydrocannabinol [THC]), or alcohol breath test.
18. Participant is unwilling to abstain from alcohol beginning 48 hours prior to the first administration of ELVN-002.
19. Use of IP or investigational medical device other than the ELVN-002, itraconazole, and phenytoin in this study within 30 days prior to Screening, or 5 half-lives of the product (whichever is the longest).
20. Use of (or anticipated use of) any prescription drugs or the medication leading to prolong the QT/QTc interval for 2 weeks prior to dosing, over-the-counter (OTC) medication, herbal remedies, supplements, or vitamins for 7 days prior to dosing, and during the study without prior approval of the PI and designee. Simple analgesia (paracetamol up to 4 g daily, ibuprofen or nonsteroidal anti-inflammatory drug [NSAID] up to 1200 mg daily) may be permitted at the discretion of the PI.
21. Intake of caffeine- or xanthine-containing products 48 hours before the first administration of IP.
22. Any intake of grapefruit, Seville oranges, pomelos, or other products containing the above-mentioned fruits within 7 days of the first administration of ELVN-002, itraconazole, and phenytoin.
23. Anything that the PI considers would jeopardise the safety of the participant, prevent complete participation in the study, or compromise interpretation of study data.
Additional exclusion criterion in Part A (SAD):
1. A participant who needs dietary requirements or special requests will be excluded.

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)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment

Other design features

Phase

Phase 1

Type of endpoint/s

Safety

Statistical methods / analysis

Recruitment

Recruitment status

Stopped early

Data analysis

Data analysis is complete

Reason for early stopping/withdrawal

Other reasons/comments

Other reasons

Sponsor stopped the trial based on SRC recommendation.

Date of first participant enrolment

Anticipated

2/05/2023

Actual

2/05/2023

Date of last participant enrolment

Anticipated

2/08/2023

Actual

22/06/2023

Date of last data collection

Anticipated

21/08/2023

Actual

16/07/2023

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment hospital [1]

Linear Clinical Research - Nedlands

Recruitment hospital [2]

Linear Clinical Research - Joondalup - Joondalup

Recruitment postcode(s) [1]

6009 - Nedlands

Recruitment postcode(s) [2]

6027 - Joondalup

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Enliven Therapeutics, Inc.

Address [1]

6200 Lookout Road, Boulder, CO 80301, US

Country [1]

United States of America

Primary sponsor type

Commercial sector/Industry

Name

Enliven Therapeutics, Inc.

Address

6200 Lookout Road, Boulder, CO 80301, US

Country

United States of America

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

Commercial sector/Industry

Name [1]

Novotech (Australia) Pty Limited

Address [1]

Level 3, 235 Pyrmont Street, Pyrmont NSW 2009

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Bellberry HREC B

Ethics committee address [1]

123 Glen Osmond Rd, Eastwood SA 5063

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

01/03/2023

Approval date [1]

03/04/2023

Ethics approval number [1]

Summary

Brief summary

This study is investigating a new cancer treatment drug, ELVN-002, that may be used for patients with lung cancer.

Who is it for?
You may be eligible for this study if you are a healthy adult aged 18 to 60 years old. Please note that this study will not be enrolling patients with lung cancer.

Study details
This registration is for Part A of a 3-part study investigating ELVN-002.

Participants in this study will be randomly allocated (3:1) to receive a single dose of ELVN-002 or a placebo. ELVN-002 will be given to you in capsule form. There will be 6 different dose levels tested. One cohort will also be asked to take a second single dose of ELVN-002 on Day 10 after consuming a high fat breakfast (food effect, FE cohort).

Total participation will last up to 7 days and 13 ± 1 for FE cohort to the clinic for physical examination and vitals assessments and to collect blood and urine samples.

It is hoped that this research will help determine the dose that ELVN-002 can be safely given to patients with lung cancer.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Ana Sun

Address

Linear Clinical Research, Level 1, B Block Hospital Avenue Nedlands, WA 6009 Australia

Country

Australia

Phone

+61 414 801 448

Fax

asun@linear.org.au

Contact person for public queries

Name

Qi Wang

Address

Enliven Therapeutics, Inc.
6200 Lookout Road, Boulder, CO 80301, US

Country

United States of America

Phone

+1 609 651 2686

Fax

qi.wang@enliventherapeutics.com

Contact person for scientific queries

Name

Helen Collins

Address

Enliven Therapeutics, Inc.
6200 Lookout Road, Boulder, CO 80301, US

Country

United States of America

Phone

+1 707 799 3272

Fax

helen.collins@enliventherapeutics.com

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically