A study to determine the safety and tolerability of graded doses of the drug LHF-535 (LHF-535-SDD) in healthy volunteers. — Recruiting Now

Conditions

Summary

A First-In-Human, Randomised, Double-Blind, Controlled, Dose-Ranging, Phase 1 Study in Healthy Volunteers aged 18-45 years. A total of up to 56 healthy male and female participants will receive one oral dose of LHF-535-SDD or placebo which consists of the inert polymer HPMCAS. The primary objective of this study is to determine the safety and tolerability of LFH-535 (LHF-535-SDD) compared to placebo controls when administered to healthy adults. LFH-535-SDD the study drug being researched in this project is an experimental drug being developed by Kineta. This means that it is not an approved treatment in Australia, and is not yet approved anywhere else in the world. LFH-535-SDD is a small molecule designed to stop the virus that causes Lassa Hemorrhagic Fever from entering the hosts cells and replicating. A maximum of 7 Cohorts will be recruited, as follow: Cohort 1: 6 participants will receive 0.3 milligrams per kilogram of body weight of LHF-535 and 2 participants will receive placebo Cohort 2: 6 participants will receive 1 milligram per kilogram of body weight of LHF-535 and 2 participants will receive placebo Cohort 3: 6 participants will receive 3 milligrams per kilogram of body weight of LHF-535 and 2 participants will receive placebo Cohort 4: 6 participants will receive 10 milligrams per kilogram of body weight of LHF-535 and 2 participants will receive placebo Cohort 5: 6 participants will receive 30 milligrams per kilogram of body weight of LHF-535 and 2 participants will receive placebo Cohort 6: optional cohort, dose to be determined by the safety committee Cohort 7: optional cohort, dose to be determined by the safety committee

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 45 Yearss

Inclusion Criteria8

Male or female 18 to 45 years of age, inclusive, at the time of screening.
Able to understand the requirements of the study, to provide written informed consent (as evidenced by signature on an informed consent document that is approved by a Human Research Ethics Committee [HREC]), and agreeable to abide by the study restrictions.
Body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive, at the time of screening and check-in (Day -1).
Minimum weight of 50 kg at the time of screening and check-in (Day -1).
Good general health (e.g., no chronic health conditions such as hypertension, diabetes, chronic obstructive pulmonary disease, or cardiovascular disease) as determined by the Investigator. Subjects with mild allergies or benign conditions such as Gilbert’s disease may be enrolled at the discretion of the Investigator.
Female subjects of child-bearing potential, with a fertile male sexual partner, must use a highly effective method of contraception (oral contraceptive, intrauterine device, or hormonal patch, injectable, or implantable device) in conjunction with a male condom during the screening period and for the entire duration of study participation including the 28-day follow-up. True abstinence from sexual intercourse, in accordance with the preferred and usual lifestyle of the subject, is acceptable. Periodic abstinence or avoiding sexual intercourse on days while the subject is fertile (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), are not acceptable methods of contraception. Non-childbearing potential is defined as postmenopausal as documented by an elevated follicle stimulating hormone (FSH) level or surgical sterility (e.g., tubal ligation, hysterectomy, and/or bilateral salpingo-oophorectomy).
Male subjects must either be surgically sterile (vasectomy) or agree to use a male condom as a method of contraception for the entire duration of the study and for 90 days after dosing; the female sexual partner must also use a medically acceptable form of birth control (e.g., oral contraceptive).
Male subjects must agree to not donate sperm for the entire duration of the study and for at least 90 days after dosing.

Exclusion Criteria18

Pregnancy or breastfeeding.
A positive screen for drugs of abuse, including alcohol. The screen may be repeated once at the Investigator’s discretion if a false-positive result is suspected.
Use of any tobacco- or nicotine-containing products (including but not limited to, cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to check-in (Day -1) or exposure to tobacco or nicotine within 30 days of check-in (Day -1).
A positive cotinine test indicating recent nicotine use. The test may be repeated once at the Investigator’s discretion if a false-positive result is suspected.
Donated blood within 90 days or plasma within 30 days of dosing on Day 1.
Active substance abuse or any medical or psychiatric condition that could jeopardize the subject’s safety.
Use of any medications apart from vitamins, acetaminophen, or hormonal contraception within 14 days of dosing on Day 1. Subjects with mild allergies may use antihistamines at the discretion of the Investigator after approval by the Sponsor Medical Monitor.
Receipt of an investigational product within 12 weeks prior to dosing on Day 1 (or 5 half-lives, whichever is longer).
Any history of cancer; non-melanoma skin cancer or cervical cancer in situ, resected surgically with no evidence of disease, may be enrolled at the discretion of the Investigator.
Receipt of an organ transplant (solid or hematopoietic), including corneal transplant.
Prolonged QTcF interval >450 ms on electrocardiograms (ECGs) collected during screening, on Day -1, or just prior to dosing on Day 1.
Other clinically significant ECG abnormality, as determined by the Investigator.
Any clinically significant abnormal hematology, chemistry, or urinalysis value, as determined by the Investigator.
Positive test for human immunodeficiency virus (HIV serology) or known HIV infection.
Positive result for hepatitis B surface antigen (HBsAg) or for hepatitis C virus (HCV) antibody.
Use of alcohol-containing foods or beverages within 72 hours prior to check-in on Day -1 or 72 hours prior to any study visit.
Use of caffeine-containing foods or beverages within 24 hours prior to check-in on Day -1 until discharge from the study unit.
Febrile illness or significant infection within 48 hours before administration of the first dose of study drug on Day 1.

Interventions

A First-In-Human, Randomised, Double-Blind, Controlled, Dose-Ranging, Phase 1 Study in Healthy Volunteers aged 18-45 years. A total of up to 56 healthy male and female participants will receive one o

A First-In-Human, Randomised, Double-Blind, Controlled, Dose-Ranging, Phase 1 Study in Healthy Volunteers aged 18-45 years. A total of up to 56 healthy male and female participants will receive one oral dose of LHF-535-SDD or placebo which consists of the inert polymer HPMCAS. Cohort 1: 6 participants will receive 0.3 milligrams per kilogram of body weight of LHF-535 and 2 participants will receive placebo Cohort 2: 6 participants will receive 1 milligram per kilogram of body weight of LHF-535 and 2 participants will receive placebo Cohort 3: 6 participants will receive 3 milligrams per kilogram of body weight of LHF-535 and 2 participants will receive placebo Cohort 4: 6 participants will receive 10 milligrams per kilogram of body weight of LHF-535 and 2 participants will receive placebo Cohort 5: 6 participants will receive 30 milligrams per kilogram of body weight of LHF-535 and 2 participants will receive placebo Cohort 6: optional cohort, dose to be determined by the safety committee Cohort 7: optional cohort, dose to be determined by the safety committee The investigational study drug, LFH-535-SDD consists of LHF-535 formulated as a spray dried dispersion (SDD) with inert polymer HPMCAS (hydroxypropylmethylcellulose acetate succinate) at a 30:70 ratio of LHF-535 to HPMCAS. The LFH-535-SDD will be suspended in the commercially available suspension vehicle Ora-Blend and will be given orally after fasting for at least 8 hours. The placebo supplied as powdered HPMCAS will be suspended in the commercially available suspension vehicle Ora-Blend and given orally after fasting for at least 8 hours. The blinded study drug suspension (LHF-535-SDD suspension or LHF-535-placebo suspension) will be administered by the blinded study personnel using a syringe (cohorts 1-3) or dosing bottle (cohorts 3-6). This will be followed by the administration of 240 mL water orally, using a portion of the water to rinse the used syringe or dosing bottle. The date and time of study drug administration will be recorded. As this is a first-in-human study, 2 sentinel participants (1 placebo and 1 LHF-535-SDD) in each cohort will receive the first dose and be monitored for 48 hours. If dosing of the sentinels proceeds with no clinically significant adverse events, the remaining participants in the cohort will be dosed. Following study drug administration, all participants will be monitored at the clinic for at least 24 hours, after which they will return to the clinic on days 4, 8, 15 and 29 to be monitored. The Investigator is responsible for product accountability during the trial and final accountability will be performed after DBL when the study is unblinded by the blinded CRA.

Locations(1)

Nucleus Network - Melbourne

VIC, Australia