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Trial registered on ANZCTR


Registration number
ACTRN12624000115538
Ethics application status
Approved
Date submitted
12/12/2023
Date registered
8/02/2024
Date last updated
4/06/2024
Date data sharing statement initially provided
8/02/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to evaluate safety, tolerability and pharmacokinetics of ELVN-001 in Normal Healthy Participants- Part A
Scientific title
A study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ELVN-001 Following Single Doses of Capsule and Tablet Administration in the Presence or Absence of High-Fat Food and/or Proton Pump Inhibitors (PPI) in Normal Healthy Participants- Part A
Secondary ID [1] 311082 0
ELVN-001-104
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myeloid Leukaemia (CML) 332232 0
Parkinson's Disease (PD) 332233 0
Condition category
Condition code
Cancer 328949 328949 0 0
Leukaemia - Chronic leukaemia
Neurological 328950 328950 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study is composed of 2 parts: This registration captures the information of PART A
• Part A (relative bioavailability [rBA] + food effect [FE]) will be conducted to assess the relative bioavailability, safety, and tolerability of ELVN-001 in healthy participants following a single dose of ELVN001 in capsule or tablet form. In addition, Part A will assess the food effect on a single dose of ELVN001 in tablet form in healthy participants.

Treatment Duration:
Part A: 15 Participants will be randomly assigned to receive a single dose of 80 mg ELVN-001 according to 1 of the 3 sequences at a ratio of 1:1:1 on Days 1, 8, and 15. either in fasting or fed conditions. Randomisation will be to 1 sequence only. An example of a high-fat, high-calorie meal would be two eggs fried in butter, two strips of bacon, two slices of toast with butter, four ounces of hash brown potatoes and eight ounces of whole milk.
- Sequence 1 will receive ELVN-001 in capsule and tablet form orally with 240 mL of water on Day 1 (capsule-fasted) and Day 8 (tablet-fasted), respectively. On Day 15 (tablet-fed), participants will consume a standardised (high-fat, high-calorie) breakfast within 30 minutes, and will then immediately (within 5 minutes of completion of the breakfast) receive ELVN-001 in tablet form orally with 240 mL of water. Participants will remain fasted for at least 4 hours after each dosing of ELVN-001 (water will be permitted 1 hour after dosing).
- Sequence 2 for Day 1, Day 8, and Day 15 will be tablet-fasted, tablet-fed and capsule-fasted.
- Sequence 3 will be tablet-fed, capsule-fasted, and tablet-fasted, respectively.

Participants who provide written informed consent will undergo Screening evaluations to determine eligibility within 28 days prior to Day -1. Eligible participants will be admitted to the clinical research unit (CRU) from Day -1 until the End of Confinement Visit/End of Study (EOS) or withdrawal from the study, whichever comes first. All the IP administrations will be done in the clinic under PI/delegate supervision who will monitor adherance to protocol.
Intervention code [1] 327534 0
Treatment: Drugs
Comparator / control treatment
Comparison is between tablet formulations and fed conditions.
Control group
Active

Outcomes
Primary outcome [1] 336746 0
To determine the relative bioavailability of ELVN-001 in capsule and tablet form following a single dose in healthy participants in Part A
Timepoint [1] 336746 0
Blood sampling for PK will be collected at a total of 42 timepoints- Pre dose and at 9 timepoints post dose on day1, day8 and day15; 24 hrs post dose on day 2, day 9 and day 16; 48 hrs post dose on day 3, day 10 and day 17; 72 hrs post dose on day 4, day 11 and day 18; 120 hrs post dose on day 6, day 13 and day 20.
Primary outcome [2] 336747 0
To evaluate the food effect on ELVN-001 PK in tablet form following a single dose in healthy participants in Part A.
Timepoint [2] 336747 0
Blood sampling for PK will be collected at a total of 42 timepoints- Pre dose and at 9 timepoints post dose on day1, day8 and day15; 24 hrs post dose on day 2, day 9 and day 16; 48 hrs post dose on day 3, day 10 and day 17; 72 hrs post dose on day 4, day 11 and day 18; 120 hrs post dose on day 6, day 13 and day 20.
Secondary outcome [1] 429536 0
To determine the safety and tolerability profile of ELVN-001 following a single dose in capsule/tablet forms in healthy participants in the presence or absence of food and/or PPI for Part A
Timepoint [1] 429536 0
Serious Adverse events (SAEs) and Adverse events (AEs): Daily from screening to day 20 (end of study)
Secondary outcome [2] 430432 0
To determine the safety and tolerability profile of ELVN-001 following a single dose in capsule/tablet forms in healthy participants in the presence or absence of food and/or PPI for Part A
Timepoint [2] 430432 0
Laboratory values will be assessed on screening, day -1, day 4, day 11 and day 20 post-first dose.
Secondary outcome [3] 430433 0
To determine the safety and tolerability profile of ELVN-001 following a single dose in capsule/tablet forms in healthy participants in the presence or absence of food and/or PPI for Part A
Timepoint [3] 430433 0
- Vital signs: Daily from screening to day 20 post first-dose (end of study)
- Triplicate 12-lead electrocardiogram (ECGs): Will be checked on screening, day -1, day 1, day 8, day 15 and day 20 post-first dose.

Eligibility
Key inclusion criteria
1. Participants more than equal to 18 and less than equal to 60 years of age at time of informed consent.
2. Normal healthy male and female participants with no clinically 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. Able to provide written informed consent to participate in this study.
4. Healthy and free from clinically significant illness or disease with clinical laboratory values at Screening and Day -1 (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.
5. Has a body mass index (BMI) more than equal to 18.5 and less than equal to 32 kg/metre square, inclusive, and weigh between more than equal to 50 kg and less than equal to 100 kg, inclusive, at Screening.
6. Able to understand the nature of the study and any risks associated with participation and willing to cooperate and comply with protocol restrictions and requirements.
7. Agrees to the meals, dietary and lifestyle requirements as outlined in the protocol.
8. Estimated glomerular filtration rate (eGFR): more than equal to 80 mL/min/1.73 metre square for all participants using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation.
9. Systolic blood pressure more than equal to 90 and less than equal to 140 mmHg and diastolic blood pressure more than equal to 40 and less than equal to 90 mmHg.
10. Resting heart rate more than equal to 45 and less than equal to 100 beats per minute (bpm).
11. A male participant must agree to use contraception, as detailed in protocol during the treatment period and for at least 90 days after the last dose of IP and refrain from donating sperm during this period or has vasectomised since at least 6 months prior to first IP administration. Male participants whose partners are woman of childbearing potential (WOCBP) can be eligible if they use condoms during intercourse and their WOCBP partners use 1 of the following contraceptive measures for at least 90 days following the last dose of IP:
• Hormonal contraception (oral, implant, or injectable),
• Intrauterine device (IUD) or intrauterine system (IUS),
• Tubal ligation, hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or
• Diaphragm or cervical cap.
12. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
• Not a woman of childbearing potential, OR
• Must agree to use contraception, as detailed in protocol, during the treatment period and for at least 90 days after the last dose of IP
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Previous participating in a trial with ELVN-001 or participating in another clinical trial within 30 days prior to first dose of the IP.
2. Received any prescribed systemic or topical medications, or live vaccination within 30 days (or less than 5 half-lives, whichever is longer) or any inactivated vaccination within 72 hours prior to first dose of the IP.
3. Potential participant has used any other IP or investigational medical device within 30 days prior to Screening.
4. Family history (biological relatives [ie, parents, siblings]) of long or short QT syndrome or Torsades de Pointes.
5. Abnormal ECG findings at Screening or Day -1 (eg, repeated demonstration of a QTc interval > 450 msec [male] or > 470 msec [female] corrected by Fridericia’s formula [QTcF] or Bazett’s formula [QTcB]) that are considered by the PI or designee to be clinically significant.
6. Presence or history of drug and or alcohol abuse including a positive result on the urine drug screen or alcohol breath test at Screening or Day -1.
7. Excessive intake of caffeine-containing drinks or food as judged by the PI. Excessive intake is defined as more than 400 mg of caffeine per day (equivalent to 4 or 5 cups of brewed coffee).
8. Use of tobacco or nicotine-containing products (including e-cigarettes) within 3 months prior to first dose of IP and during the course of the study.
9. Test positive for hepatitis B surface antigen, hepatitis B core antibody, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) 1 and HIV 2 antibodies. If a participant tests positive for HCV antibodies, they may still be allowed into the trial if HCV ribonucleic acid (RNA) is undetectable in a Follow-up assessment.
10. Plasma donation within 30 days of Screening or any blood/loss or donation more than 500 mL during the 90 days prior to Screening.
11. History or presence of gastrointestinal (including a previous episode of pancreatitis), hepatic, or renal disease, or any other conditions known to interfere with absorption, distribution, metabolism, or excretion of drugs.
12. Unwillingness to refrain from strenuous exercise 48 hours prior to CRU confinement and for the duration of the study.
13. Positive cotinine test at Screening and Day -1.
14. Is at suicidal risk in the opinion of the PI as per the following criteria:
• Any suicidal attempts within 12 months prior to Screening.
• Any suicidal intent including a plan or Columbia-Suicide Severity Rating Scale (C-SSRS) answer of “YES” on suicidal ideation currently or within 3 months.
15. Is unable to consume a high-fat, high-calorie meal.
16. Unwillingness to abstain from concomitant therapy for the duration of the study (with the exception of medications used to treat adverse symptoms associated with ELVN-001 administration and permitted contraception [outlined in protocol. Over the counter (OTC) medications, topical medications, herbal remedies, supplements, or vitamins are not permitted for 7 days prior to dosing, and during the study without prior approval of the PI or designee.

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)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
17/10/2024
Actual
Date of last participant enrolment
Anticipated
17/10/2024
Actual
Date of last data collection
Anticipated
5/11/2024
Actual
Sample size
Target
15
Accrual to date
Final
Recruitment outside Australia
Country [1] 26007 0
New Zealand
State/province [1] 26007 0
Auckland

Funding & Sponsors
Funding source category [1] 315339 0
Commercial sector/Industry
Name [1] 315339 0
Enliven Therapeutics, Inc.
Country [1] 315339 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] 317403 0
None
Name [1] 317403 0
None
Address [1] 317403 0
Country [1] 317403 0
Other collaborator category [1] 282888 0
Commercial sector/Industry
Name [1] 282888 0
Novotech(Australia) Pty Limited
Address [1] 282888 0
Level 19/66 Goulburn Street, Sydney, NSW, 2000
Country [1] 282888 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314262 0
Northern B Health and Disability Ethics Committees
Ethics committee address [1] 314262 0
Ministry of Health, Health and Disability Ethics Committees, PO Box 5013, Wellington 6140
Ethics committee country [1] 314262 0
New Zealand
Date submitted for ethics approval [1] 314262 0
23/11/2023
Approval date [1] 314262 0
19/12/2023
Ethics approval number [1] 314262 0
2023 FULL 19150

Summary
Brief summary
The current study is being conducted in healthy participants to understand the appropriate drug dosage form and administration of ELVN-001. This study plans to assess the relative bioavailability of ELVN-001 in capsule and tablet forms, the safety profile of ELVN-001, and the effects of food and/or proton pump inhibitors (PPIs) on ELVN-001.

Who is it for?
Participants who provide written informed consent will undergo screening evaluations and only eligible participants will be admitted to the clinical research unit (CRU) from Day -1 until the End of Confinement Visit/End of Study (EOS) or withdrawal from the study, whichever comes first.

Study details
Participants are healthy participants between age of 18-60yrs with the BMI of more than equal to 18.5 and less than equal to 32 kg/m2 inclusive, and weigh between more than equal to 50 kg and less than equal to 100 kg, inclusive, at Screening.
The study will be conducted in with healthy participants (15 in Part A). All doses of ELVN-001 for Part A will be administered at the CRU in the presence of the PI or their designee.

Study duration
It is estimated that overall study duration to be approximately 9 months. Estimated study duration for each participant (including the screening period) is approximately 48 days.

It is hoped that this research will help determine the appropriate drug dosage form and administration of ELVN-001 and inform further clinical use of ELVN-001 in patients with CML and other therapeutic areas, such as PD.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 130974 0
Dr Laura Elliott
Address 130974 0
New Zealand Clinical Research, 3 Ferncroft Street, Grafton, Auckland 1010
Country 130974 0
New Zealand
Phone 130974 0
+64 9 373 3474
Fax 130974 0
Email 130974 0
laura.elliott@nzcr.co.nz
Contact person for public queries
Name 130975 0
Dr Laura Elliott
Address 130975 0
New Zealand Clinical Research, 3 Ferncroft Street, Grafton, Auckland 1010
Country 130975 0
New Zealand
Phone 130975 0
+64 0800 788 3437
Fax 130975 0
Email 130975 0
Pinnacle.auckland@nzcr.co.nz
Contact person for scientific queries
Name 130976 0
Ms Helen Collins
Address 130976 0
Enliven Therapeutics, Inc. 6200 Lookout Road, Boulder, CO 80301, US
Country 130976 0
United States of America
Phone 130976 0
+1 707 321 8168
Fax 130976 0
Email 130976 0
helen.collins@enliventherapeutics.com

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.