None listed
Conditions
Brief summary
This study aims to assess the safety, and tolerability of ELVN-001 in healthy participants following a single and multiple ascending doses of ELVN-001 or matching placebo in three parts Part A (SAD), Part B (MAD) and Part C (FE) Who is it for? You may be eligible for this study if you are a healthy adult aged between 18 and 60 years old. Please note that Normal healthy male and female participants with no clinically significant medical history, and no clinically significant abnormalities on physical examination at Screening will be enrolled for this study. Study details This is a Double-Blinded, Randomized, Placebo-Controlled, Single- and Multiple- Ascending Dose Study To Assess The Safety, Tolerability, and Pharmacokinetics of ELVN-001 in Normal Healthy Participants. Part A (Single Ascending Dose): Participants will be randomly assigned to receive ELVN-001 or matching placebo at a ratio of 6:2. Participants in the Part A (SAD) will receive a single dose of ELVN-001 or matching placebo on Day 1 after a minimum 10 hour fast. Participants in Part A will remain fasted for at least 4 hours after dosing. Part B (Multiple Ascending Dose): Participants will be randomly assigned to receiving ELVN-001 or matching placebo at a ratio of 6:2. Participants in the Part B (MAD) will receive a daily dose of ELVN-001 or matching placebo after a minimum 2 hour fast from Day 1 to Day 10. Participants in Part B will also remain fasted for at least 1 hour post-dose. Blood samples will be drawn from participants on every day of the study. It is hoped that this research will determine the safe maximum dose of ELVN-001 that can be trialled as a therapy for patients with chronic myeloid leukamia. Part C (Food Effect) After SAD Cohort 5(120mg), 12 Participants will be randomly assigned to sequence 1(S1) or sequence 2(S2) with a ratio of 1:1. Participants in S1 will receive a single oral dose of 120mg ELVN-001 on Day 1 in fasted conditions and Day 6 in fed conditions and in S2 will receive a single oral dose of 120mg ELVN -001 (with water 240mL) on Day 1 in fed conditions and Day 6 in fasting conditions.
Interventions
ELVN-001 is a potent, adenosine triphosphate (ATP)-competitive small molecule inhibitor of the cytoplasmic Abelson Tyrosine Kinase (ABL, also known as Abl1 or c-Abl). Constitutional activation of ABL has been implicated in leukemia and neurodegenerative diseases.
Investigational Product: ELVN-001
Dosage Formulation: ELVN-001 will be supplied in two formats: one containing 10 mg ELVN-001 capsules, the other containing 40 mg ELVN-001 capsules
Route of Administration: Oral
The study is composed of
ELVN-001 is a potent, adenosine triphosphate (ATP)-competitive small molecule inhibitor of the cytoplasmic Abelson Tyrosine Kinase (ABL, also known as Abl1 or c-Abl). Constitutional activation of ABL has been implicated in leukemia and neurodegenerative diseases. Investigational Product: ELVN-001 Dosage Formulation: ELVN-001 will be supplied in two formats: one containing 10 mg ELVN-001 capsules, the other containing 40 mg ELVN-001 capsules Route of Administration: Oral The study is composed of 3 parts: Part A (Single Ascending Dose [SAD]) will be conducted to assess the PK, safety, and tolerability of ELVN-001 in healthy participants following a single dose of ELVN-001 or matching placebo at a ratio of 6:2 in each cohort. Seven cohorts will be included in Part A where a single dose of ELVN-001 will be administered per cohort. Part B (Multiple Ascending Dose [MAD]) will be conducted to assess the PK, safety, and tolerability of ELVN-001 in healthy participants following a daily dose of ELVN-001 administered over 10 days of the study or matching placebo at a ratio of 6:2 in each cohort Part c (Food Effect[FE]) will be conducted to assess the food effect on the PK, safety and tolerability of ELVN-001 following a single dose in healthy participants In Part A, Single Ascending Dose (SAD), Participants will receive a single dose of ELVN-001 or matching placebo on Day 1 after a minimum 10 hour fast. Cohort 1: Participant will receive 10 mg of ELVN-001 once on Day 1 Cohort 2: Participant will receive 20 mg of ELVN-001 once on Day 1 Cohort 3: Participant will receive 40 mg of ELVN-001 once on Day 1 Cohort 4: Participant will receive 80 mg of ELVN-001 once on Day 1 Cohort 5: Participant will receive 120 mg of ELVN-001 once on Day 1 Cohort 6: Participant will receive 160mg of ELVN-001 once on Day 1 Cohort 7 (optional) : Participant will receive 200mg of ELVN-001 once on Day 1 Treated participants in Part A (SAD) will be confined to the Clinical Research Unit from Day -1 through to Day 6 (inclusive), until all required assessments have been performed and there is no medical reason for a longer stay in the Clinical Research Unit (CRU). After eligibility determination at both Screening and Day -1, the participants will be admitted to the Clinical Research Unit (CRU) on Day -1 and will start fasting for at least 10 hours before the dosing on Day 1. Participants in the Part B (MAD) will receive a daily dose of ELVN-001 or matching placebo after a minimum 2 hour fast from Day 1 to Day 10. Participants in Part B will also remain fasted for at least 1 hour post dose. Participants will be confined to the Clinical Research Unit (CRU), from Day -1 to Day 11, until all required assessments have been performed and there is no medical reason for a longer stay in the Clinical Research Unit (CRU), based on the Investigator’s discretion. A study monitor will be identified and will be responsible. Enrolment into the Part B (MAD [ie, MAD Cohort 1]) may be initiated concomitantly with Part A (SAD) Cohort 2, after the dose regimens in Part A (SAD) Cohort 1 to Cohort 4 have been recommended by the Safety Review Committee (SRC) to be safe and well tolerated. SRC decisions on dose escalation during Part B (MAD) will be based on safety and tolerability data from each cohort. Participants in Part c (Food Effect)- Target sample size- 88 After SAD Cohort 5(120mg), Participants will be randomly assigned to sequence 1(S1) or sequence 2(S2) with a ratio of 1:1. Participants in S1 will receive a single oral dose of 120mg ELVN-001(with water 240 mL) on Day 1 in fasted conditions and Day 6 in fed conditions and in S2 will receive a single oral dose of 120mg ELVN -001 (with water 240mL) on Day 1 in fed conditions and Day 6 in fasting conditions. Participants in Part C (FE) will be confined to the CRU from Day -1 through to Day 9 (inclusive), until all required assessments have been performed and there is no medical reason for a longer stay in the CRU, based on the Investigator’s discretion. For the fed period, Participants will consume a high-fat, high-calorie breakfast, as recommended by the U.S. Food and Drug Administration (FDA 2022), following an overnight fast of at least 10 hours. The high-fat, high calorie meal will follow that if the US FDA guidance (FDA 2022). Approximately 50% of total caloric content of the meal should be from fat and the meal approximately 800 to 1000 calories in total. A typical meal is 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. This meal derives approximately 150, 250, and 500-600 calories from protein, carbohydrates and fat, respectively. ELVN-001 will be administered orally within 30 minutes after the participants begin consuming the meal. Participants will continue fasting for at least 4 hours after dosing (water intake will be permitted from 1 hour after dosing). For the fasted period, ELVN-001 will be administered orally following an overnight fast of at least 10 hours. Participants will continue fasting for at least 4 hours after dosing (water intake will be permitted from 1 hour after dosing)
Sponsors
Enliven Therapeutics, Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
To be eligible for this study, a participant must meet all of the following inclusion criteria: Age 1. Participants greater than and equal to 18 to lesser than 60 years of age at time of informed consent. Type of Patient and Disease Characteristics 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 General Inclusion Criteria 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. Have a body mass index (BMI) between 18.5 and 30 kg/m2 , inclusive, and weigh at least 50 kg and no more than 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 protocol restrictions and requirements. 7. Agrees to the meals, dietary and lifestyle restrictions outlined in the protocol during the course of the study. 8. Estimated glomerular filtration rate (eGFR): more than 89 mL per min per 1.73 meter square for participants 18 to 59 years old, or more than 84 mL per min per 1.73 meter square for participants 60 years old) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation. 9. Systolic blood pressure of 90 to 140 mmHg and diastolic blood pressure of 40 to 90 mmHg. 10. Resting heart rate of 45 to 100 beats per minute (bpm). Reproductive Status Male participants: 11. A male participant must agree to use contraception, during the treatment period and for at least 90 days after the last dose of IP and refrain from donating sperm during this period. Male participant whose partners are Women of Child bearing potential (WOCBP) can be eligible if they use condoms during intercourse and their WOCBP partners use one of the following contraceptive measures for at least 90 days following the last dose of IP. • Hormonal contraception (oral, implant, injectable) Intrauterine device (IUD) or intrauterine system (IUS) • Tubal ligation • Simultaneous use of diaphragm or cervical cap and male condom for the male partner Female participants: 12. A female participant is eligible to participate if she is not pregnant, not breastfeeding and at least one of the following conditions applies: • Not a woman of childbearing potential, OR • Must agree to use contraception, as detailed in the protocol, during the treatment period and for at least 90 days after the last dose of IP.
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply. No waivers will be granted. 1. Previous participating a trial with ELVN-001. 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 more than 450 ms (male) or more 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. 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 Investigator. Excessive intake is defined as more than 400 mg of caffein per day (equivalent to 4 or 5 cups of brewed coffee). 8. Use of tobacco or nicotine-containing products 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 & 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. A female participant is pregnant or breastfeeding. 13. Unwillingness to refrain from strenuous exercise 48 hours prior to CRU confinement and for the duration of the study. 14. History of lactose intolerance. 15. Positive cotinine test at Screening or Day -1. 16. 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. For Part C (FE) Only: 17. A participant who is unable to consume a high-fat, high calorie breakfast (containing eggs, butter, bacon, white bread, hash browns, and whole milk). Prior/Concomitant Therapy 18. 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). Over the counter (OTC) medication, herbal remedies, supplements, or vitamins are not permitted for 7 days prior to dosing, and during the study without prior approval of the PI and designee.
Outcome results
None listed