ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12624000535572p

Ethics application status

Submitted, not yet approved

Date submitted

28/03/2024

Date registered

30/04/2024

Date last updated

30/04/2024

Date data sharing statement initially provided

30/04/2024

Type of registration

Prospectively registered

Titles & IDs

Public title

A Phase I, Randomized, Placebo-Controlled, First in Human Study of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of LTSE-2578 in Healthy Participants

Scientific title

A Phase I, Randomized, Placebo-Controlled, First in Human Study of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of LTSE-2578 in Healthy Participants

Secondary ID [1]

LTSE-2578-01

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

Idiopathic pulmonary fibrosis

Condition category

Condition code

Respiratory

Other respiratory disorders / diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The study will be conducted in 2 parts:
Part 1: Single ascending dose (SAD)
Part 2: Multiple ascending dose (MAD)
Decisions about how and when to move between cohorts will be based on reviews of the available safety data (blinded) and pharmacokinetic data.

Part 1: Each cohort will enrol 8 participants with 6 participants randomized to receive LTSE-2578 and 2 participants randomized to receive placebo on Day 1. There will be 5 cohorts and LTSE-2578 oral tablet will be administered at dose levels in the range of 6mg - 250mg.

SAD Cohort 4 – food effect cohort: Single oral dose of LTSE-2578 or placebo administered on Day 1 under fasted conditions and another dose administered on Day 5 under fed conditions (total of 2 doses).

Part 2: LTSE-2578 oral tablet administered twice daily for 14 days at up to 3 dose levels (3 cohorts) in the range from 20 mg to up to 200 mg (total daily dose; actual dosage to be determined based on data from Part 1 and the preceding cohorts in Part 2). Each cohort will enrol 8 participants with 6 participants randomized to receive LTSE-2578 and 2 participants randomized to receive placebo.

Study drug will be administered at the study site by trained study site personnel to ensure compliance.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Tablets of matching appearance and formulation to the investigational product, however without the LTSE-2578 active ingredient, will be administered as placebo in this study.

Control group

Placebo

Outcomes

Primary outcome [1]

Composite outcome: To assess the safety and tolerability of a single dose of LTSE 2578 in healthy adult participants

Timepoint [1]

Adverse events - will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (Version 5) and assessed continuously as they are reported or observed and reviewed daily from Day - 1 until Day 15 (End of Study/Early Termination visit [EOS/ETV]).

Vital signs - Blood pressure and heart rate is measured using sphygmomanometer, respiratory rate by manual breath count and temperature by thermometer. Assessed at Screening, Day -1, pre-dose Day 1 0.5, 2, 6 & 12 hrs post-dose, Day 2 24 hrs post-dose, Day 3 48 hrs post-dose, Day 4 72 hrs post-dose and Day 15 (End of Study/Early Termination visit [EOS/ETV]).

Electrocardiogram (ECG) - 12-lead ECG recordings will be obtained in triplicate at Screening, Day -1, Day 3 48 hrs post-dose, Day 4 72 hrs post-dose and Day 15 (End of Study/Early Termination visit [EOS/ETV]).

Clinical laboratory evaluations - blood and urine samples will be collected from Screening, Day -1, Day 1 6 hrs post-dose, Day 2 24 hrs post-dose, Day 3 48 hrs post-dose and Day 15 (End of Study/Early Termination visit [EOS/ETV]).

Primary outcome [2]

Composite Outcome: To assess the safety and tolerability of repeat doses of LTSE 2578 in healthy adult participants

Timepoint [2]

Adverse events - will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (Version 5) and assessed continuously as they are reported or observed and reviewed daily from Day - 1 until Day 28 (End of Study/Early Termination visit [EOS/ETV]).

Vital signs - Blood pressure and heart rate is measured using sphygmomanometer, respiratory rate by manual breath count and temperature by thermometer. Assessed at Screening, Day -1, pre-dose Day 1 0.5, 2, 6 & 12 hrs post-dose, pre-dose on Day 2 through to Day 14 0.5, 2, 6, 12 hrs post dose, Day 15 24 hrs post dose, Day 16 48 hrs post dose, Day 17 72 hrs post-dose and Day 28 (End of Study/Early Termination visit [EOS/ETV]).

Electrocardiogram (ECG) - 12-lead ECG recordings will be obtained in triplicate at Screening, pre-dose Day 2, pre-dose Day 5, pre-dose Day 8, pre-dose Day 11, Day 16 48 hrs post-last dose, Day 17 72 hrs post-last dose and Day 28 (End of Study/Early Termination visit [EOS/ETV]).

Clinical laboratory evaluations - blood and urine samples will be collected from Screening, Day -1, Day 1 6 hrs post-dose, pre-dose on Days 2, 5, 8 and Day 11, Day 15 24 hrs post-last dose and Day 28 (End of Study/Early Termination visit [EOS/ETV]).

Secondary outcome [1]

To describe the PK profile in plasma following a single dose of LTSE 2578 in healthy adult participants

Timepoint [1]

Blood samples will be collected as follows: pre-dose Day 1, 0.25hrs, 0.5 hrs, 1 hr, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs and 12 hrs post-dose, Day 2 24 hrs post-dose, Day 3 48 hrs post-dose, Day 4 72 hrs post-dose.

Secondary outcome [2]

To describe the PK profile in plasma following repeat doses of LTSE 2578 in healthy adult participants

Timepoint [2]

Blood samples will be collected as follows: pre-dose Day 1, 0.25 hrs, 0.5 hrs, 1 hr, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs and 12 hrs post-dose, Day 2 24 hrs post-dose, pre-dose on Days 3, 5, 7, 12 and 13, pre-dose Day 14, 0.25 hrs, 0.5 hrs, 1 hr, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs and 12 hrs post-dose, Day 15 24 hrs post-dose, Day 16 48 hrs post-dose, Day 17 72 hrs post-dose.

Secondary outcome [3]

To examine dose proportionality following a single dose of LTSE 2578

Timepoint [3]

Blood plasma samples will be collected as follows: pre-dose Day 1, 0.25hrs, 0.5 hrs, 1 hr, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs and 12 hrs post-dose, Day 2 24 hrs post-dose, Day 3 48 hrs post-dose, Day 4 72 hrs post-dose.

Secondary outcome [4]

To examine dose proportionality following repeated doses of LTSE 2578

Timepoint [4]

Blood plasma samples will be collected as follows: pre-dose Day 1, 0.25 hrs, 0.5 hrs, 1 hr, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs and 12 hrs post-dose, Day 2 24 hrs post-dose, pre-dose on Days 3, 5, 7, 12 and 13, pre-dose Day 14, 0.25 hrs, 0.5 hrs, 1 hr, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs and 12 hrs post-dose, Day 15 24 hrs post-dose, Day 16 48 hrs post-dose, Day 17 72 hrs post-dose.

Secondary outcome [5]

To assess accumulation of LTSE 2578 (Part 1)

Timepoint [5]

Secondary outcome [6]

To assess accumulation of LTSE 2578 (Part 2)

Timepoint [6]

Secondary outcome [7]

To assess time to steady-state of LTSE 2578 (Part 2)

Timepoint [7]

Blood plasma samples will be collected as follows: pre-dose Days 2 3, 5, 7, 12, 13 and 14.

Secondary outcome [8]

To assess the PK of LTSE-2578 in urine following administration of a single oral dose in healthy adult participants (Part 1 SAD only, Cohort 4 – fasted period 1 only).

Timepoint [8]

Urine samples will be collected as follows for Part 1 Cohort 4 (fasted period 1 only): Day 1 pre-dose, Day 1 post dose: 0-6 hrs, 6-12 hrs, 12-24 hrs, Day 2 post dose 24-48 hrs, Day 3 post dose 48-72 hrs.

Secondary outcome [9]

To assess the effect of food on the PK of LTSE-2578 under fasted and fed conditions (Part 1 SAD Cohort 4 only)

Timepoint [9]

Blood samples will be collected as follows for Part 1 Cohort 4: pre-dose Day 1, 0.25 hrs, 0.5 hrs, 1 hr, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs and 12 hrs post-dose, Day 2 24 hrs post-dose, Day 3 48 hrs post-dose, Day 4 72 hrs post-dose, pre-dose Day 5, 0.25 hrs, 0.5 hrs, 1 hr, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs and 12 hrs post-dose, Day 6 24 hrs post-dose, Day 7 48 hrs post-dose, Day 8 72 hrs post-dose,

Eligibility

Key inclusion criteria

1. Adult males and females, 18 to 65 years of age (inclusive) at screening.
2. Body mass index (BMI) greater than or equal to 18.0 and less than or equal to 30.0 kg/m2, with a body weight (to 1 decimal place) greater than or equal to 40 kg at screening.
3. Medically healthy (in the opinion of the Investigator) at screening, as determined by pre-study medical history, and without clinically significant abnormalities including:
a. Physical examination without any clinically relevant findings;
b. Systolic blood pressure in the range of 90 to 140 mmHg and diastolic blood pressure in the range of 50 to 90 mmHg after 5 minutes in supine or semi-supine position.
c. Pulse rate in the range of 40 to 100 bpm after 5 minutes rest in supine or semi-supine position.
d. Body temperature (tympanic), between 35.5°C and 37.5°C.
e. Electrocardiogram (ECG) without clinically significant abnormalities including QRS interval >120 msec on the screening ECG (measurements are the mean of 3 ECGs), QT interval corrected for Fredericia (QTcF) <450 msec for male subjects and <470 msec for female subjects.
f. No clinically significant findings in serum chemistry, haematology, coagulation and urinalysis tests including the following specific findings:
i. Alanine aminotransferase (ALT) <1.5 x ULN, aspartate aminotransferase (AST) <1.5 x ULN, gamma-glutamyl transferase (GGT) <1.5 x ULN, or alkaline phosphatase <1.5 x ULN .
4. Female volunteers (Childbearing or non-childbearing potential):
a. Non-childbearing potential is defined as surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks before the screening visit or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or
b. If of child-bearing potential, must:
i. Have a negative pregnancy test at the screening visit and on admission to the clinic on Day-1.
ii. Agree not to attempt to become pregnant or donate ova from signing the consent form until at least 90 days after the last dose of study drug.
iii. If not exclusively in a same-sex relationship or abstinent as a committed lifestyle, agree to use adequate contraception (defined as use of a condom by the male partner combined with use of a highly effective method of contraception from one month prior to screening until at least 90 days after the last dose of study drug.
5. Male volunteers, must:
a. Agree not to donate sperm from signing the consent form until at least 90 days after the last dose of study drug.
b. If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception (defined as use of a condom combined with use of a highly effective method of contraception from signing the consent form until at least 90 days after the last dose of study drug.
c. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, agree to use a condom from signing the consent form until at least 90 days after the last dose of study drug.

Minimum age

18 Years

Maximum age

65 Years

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

1. Known hypersensitivity to any of the study drug ingredients.
2. Demonstrated clinically significant (required intervention, e.g., emergency room visit, epinephrine administration) allergic reactions (e.g., food, drug, or atopic reactions, asthmatic episodes) which, in the opinion of the Investigator, would interfere with the volunteer’s ability to participate in the trial.
3. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic, psychiatric or neurological disease/disorder, including any acute illness, within the past 3 months determined by the Investigator to be clinically relevant.
4. History of surgery or hospitalization within 2 months prior to screening, or surgery planned during the study.
5. Any history of malignant disease in the last 5 years (excludes surgically resected skin squamous cell, basal cell carcinoma and cervical cancer in situ).
6. History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrythmia.
7. Presence or having sequelae of gastrointestinal, liver (including Gilbert’s syndrome), kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
8. Estimated creatinine clearance (CrCl) < 60 mL/min using the Cockcroft-Gault formula or serum creatinine more than 1.5-fold above the ULN at screening.
9. Positive test results for active human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit.
10. Positive drugs of abuse test, cotinine test or alcohol breath test results at the screening visit or on admission to the clinic on Day -1.
11. Regular consumption of more than 10 standard alcoholic drinks/week, where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer [4.9% Alc/Vol], 100 mL wine [12% Alc/Vol], or 30 mL spirit [40% Alc/Vol]).
12. Any history of smoking or nicotine use (e.g., cigarettes, e-cigarettes/vaping, marijuana, cigars, chewing, or nicotine replacement therapy) within 3 months prior to screening .
13. Consumption of grapefruit, tangelo, or Seville orange (or products containing grapefruit or Seville orange) within 10 days prior to dosing (Day 1).
14. Females who are breastfeeding or planning to breastfeed.
15. Use of any prescription or over-the-counter medication (including herbal products, diet aids, vitamins, and hormone supplements) within 10 days or 5 half-lives of the medication (whichever is longer) prior to the first dose of study drug, except use of contraceptives and the occasional use of paracetamol (up to 2 g per day).
16. Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medication within 10 days prior to first dose of study drug.
17. Use of any vaccinations within 30 days prior to screening.
18. Donation of blood or plasma within 30 days prior to first dose of study drug, or loss of whole blood of more than 500 mL within 30 days prior to first dose of study drug, or receipt of a blood transfusion within 1 year of the first dose of study drug.

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)

Participants will be randomized to receive LTSE-2578 or Placebo according to the randomisation schedule and plan prepared prior to study start. Code-break tamper-evident envelopes containing treatment allocation per participant will be provided to the study site for emergency unblinding if required.

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

Participants who meet the study eligibility criteria will be assigned a randomisation number pre-dose on Day 1, which corresponds to a study treatment (LTSE-2578 or placebo). The allocation to LTSE-2578 or placebo will be performed using a block randomisation algorithm and will be documented in the study randomisation schedule.

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

11/06/2024

Actual

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Scientia Clinical Research - Randwick

Recruitment postcode(s) [1]

2031 - Randwick

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Lhotse Bio, Inc.

Address [1]

Country [1]

United States of America

Primary sponsor type

Commercial sector/Industry

Name

Lhotse Bio, Inc.

Address

Country

United States of America

Secondary sponsor category [1]

Commercial sector/Industry

Name [1]

Avance Clinical Pty Ltd

Address [1]

Country [1]

Australia

Ethics approval

Ethics application status

Submitted, not yet approved

Ethics committee name [1]

Bellberry Human Research Ethics Committee D

Ethics committee address [1]

https://bellberry.com.au/

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

10/04/2024

Approval date [1]

Ethics approval number [1]

Summary

Brief summary

This is a double-blind, randomized, placebo-controlled study which is subdivided in 2 parts, Part 1 (SAD) and Part 2 (MAD). Decisions about how and when to move between cohorts will be based on reviews of the available blinded safety data and available pharmacokinetic (PK) data; this data will be reviewed by a prespecified Safety Review Committee (SRC). In Part 1, healthy volunteers will be enrolled to receive single ascending doses of LTSE-2578 or placebo. In Part 2, healthy volunteers will be enrolled to receive once or twice daily doses of LTSE-2578 or placebo for fourteen consecutive days.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Christopher Argent

Address

Scientia Clinical Research, 5th Floor Bright Building, Corner High and Avoca Street, Randwick NSW 2031

Country

Australia

Phone

+61 02 9382 5844

Fax

[email protected]

Contact person for public queries

Name

Christopher Argent

Address

Scientia Clinical Research, 5th Floor Bright Building, Corner High and Avoca Street, Randwick NSW 2031

Country

Australia

Phone

+61 02 9382 5844

Fax

[email protected]

Contact person for scientific queries

Name

Christopher Argent

Address

Scientia Clinical Research, 5th Floor Bright Building, Corner High and Avoca Street, Randwick NSW 2031

Country

Australia

Phone

+61 02 9382 5844

Fax

[email protected]

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

Documents added manually

Documents added automatically