Trial Review

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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] 309147 0
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 329254 0
Condition category
Condition code
Cancer 326207 326207 0 0
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] 325595 0
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] 334085 0
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] 334085 0
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] 334087 0
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] 334087 0
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] 334530 0
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] 334530 0
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] 419311 0
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] 419311 0
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] 419312 0
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] 419312 0
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] 421009 0
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] 421009 0
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] 421010 0
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] 421010 0
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).

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
48
Accrual to date
Final
34
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 24214 0
Linear Clinical Research - Nedlands
Recruitment hospital [2] 24215 0
Linear Clinical Research - Joondalup - Joondalup
Recruitment postcode(s) [1] 39747 0
6009 - Nedlands
Recruitment postcode(s) [2] 39748 0
6027 - Joondalup

Funding & Sponsors
Funding source category [1] 313349 0
Commercial sector/Industry
Name [1] 313349 0
Enliven Therapeutics, Inc.
Country [1] 313349 0
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] 315096 0
None
Name [1] 315096 0
Address [1] 315096 0
Country [1] 315096 0
Other collaborator category [1] 282580 0
Commercial sector/Industry
Name [1] 282580 0
Novotech (Australia) Pty Limited
Address [1] 282580 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 282580 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312570 0
Bellberry HREC B
Ethics committee address [1] 312570 0
Ethics committee country [1] 312570 0
Australia
Date submitted for ethics approval [1] 312570 0
01/03/2023
Approval date [1] 312570 0
03/04/2023
Ethics approval number [1] 312570 0

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

Contacts
Principal investigator
Name 125130 0
Dr Ana Sun
Address 125130 0
Linear Clinical Research, Level 1, B Block Hospital Avenue Nedlands, WA 6009 Australia
Country 125130 0
Australia
Phone 125130 0
+61 414 801 448
Fax 125130 0
Email 125130 0
[email protected]
Contact person for public queries
Name 125131 0
Qi Wang
Address 125131 0
Enliven Therapeutics, Inc.
6200 Lookout Road, Boulder, CO 80301, US
Country 125131 0
United States of America
Phone 125131 0
+1 609 651 2686
Fax 125131 0
Email 125131 0
[email protected]
Contact person for scientific queries
Name 125132 0
Helen Collins
Address 125132 0
Enliven Therapeutics, Inc.
6200 Lookout Road, Boulder, CO 80301, US
Country 125132 0
United States of America
Phone 125132 0
+1 707 799 3272
Fax 125132 0
Email 125132 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.