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Trial registered on ANZCTR


Registration number
ACTRN12618001823268
Ethics application status
Approved
Date submitted
3/11/2018
Date registered
9/11/2018
Date last updated
20/01/2020
Date data sharing statement initially provided
9/11/2018
Date results information initially provided
15/10/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and tolerability Phase I study of LBS-008 in healthy adult subjects after single and multiple doses
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LBS-008 in Healthy Adult Subjects
Secondary ID [1] 296467 0
LBS-008-CT01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dry age-related macular degeneration 310253 0
Condition category
Condition code
Eye 308977 308977 0 0
Normal eye development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The Single Ascending Dose (SAD) portion will have up to 5 cohorts and up to a total of 40 subjects (8 subjects per cohort). The starting dose of LBS-008 will be 50 mg and the planned doses for subsequent cohorts are 100, 200, 400 mg. An additional cohort at 25 mg dose level is determined to further evaluate the safety, PK and PD profile of LBS-008.

The Multiple Ascending Dose (MAD) portion will start after the completion of Cohort 4 of SAD and will have up to 4 cohorts and up to a total of 32 subjects (8 subjects per cohort). The starting dose of LBS-008 will be 10 mg and the planned doses for subsequent cohorts are 25, 5 and 12 mg. The final doses are determined based on the outcome of SAD portion.

Route of administration: Oral
Duration: SAD on Day 1 and MAD from day 1 to day 14

The strategies used to monitor adherence to the study drug will be: administration under direct medical supervision, mouth inspection for checking the ingestion, appropriate record of the dosing information, counts of the number of capsules.
Intervention code [1] 312791 0
Treatment: Drugs
Comparator / control treatment
Placebo (microcrystalline cellulose capsule) controlled treatment.
Control group
Placebo

Outcomes
Primary outcome [1] 307957 0
Evaluate the safety and tolerability to LBS-008, access by adverse events, clinical laboratory test result, vital sign measurement, physical examination and 12-lead ECG result.
Timepoint [1] 307957 0
Monitored daily through Day 8 for SAD; Monitored daily through Day 21 for MAD.
Primary outcome [2] 307994 0
To evaluate the ocular safety by access the slit lamp biomicroscopy, dilated ophthalmoscopy, and intraocular pressure, visual acuity and color vision result.
Timepoint [2] 307994 0
Monitored daily through day 2 and day 8 of SAD; Monitored on Day 2, 7, 16 and 21 of MAD.
Primary outcome [3] 308027 0
Pharmacokinetics (PK) parameters (AUC0-t, AUC0-inf, Cmax, Tmax, lambda z, t1/2, CL/F, and Vz/F) of administration of LBS-008 subjects.
Timepoint [3] 308027 0
Blood PK will be collected at Day 1, 2, 3, 4, 5, 6 and 8 after IP administration of SAD. Blood PK will be collected at Day 1, 2, 3, 4, 7, 11, 14, 15, 16, 17, 18, 19, 21 and 28 for MAD after IP administration.
Secondary outcome [1] 353471 0
1. To determine the effects of LBS-008 on plasma levels of RBP4, a PD marker.
Timepoint [1] 353471 0
Blood collection of RBP4 for SAD will be on Day 1, 2, 3, 4, 5, 6 and 8 after IP administration and on day 1, 2, 3, 4, 7, 11, 14, 15, 16, 17, 18, 19, 21 and 28 for MAD after IP administration.

Eligibility
Key inclusion criteria
1.The subject is male or female, 18 to 65 years of age, inclusive, at screening.
2. The subject voluntarily consents to participate in this study and provides written informed consent before the start of any study-specific procedures.
3. The subject is willing and able to remain in the study unit for the entire duration of the confinement period and return for outpatient visits.
4. Female subjects must be of nonchildbearing potential (defined as surgically sterile [i.e., had a bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 6 months before the dose of study drug] or postmenopausal for at least 1 year before study drug administration confirmed by FSH test at screening; FSH level >40 mIU/mL). Female subjects may also be considered of non-childbearing if they have a confirmed medical condition which would deem the subject as infertile. E.g. MRKH Syndrome (Mullerian Agenesis) or another applicable condition.
5. Male subjects must be surgically sterile (i.e., vasectomy) for at least 3 months before screening; or remain abstinent or agree to use a highly effective form of contraception when sexually active with a female partner for 90 days after study drug administration. Highly effective contraception requires use of a condom and appropriate contraceptive measures for your female partner (i.e. oral, injected or implanted hormonal methods, or placement of an intrauterine device or intrauterine system). This requirement does not apply to subjects in a same sex relationship and female partners of non-childbearing potential.
6. The subject has a body mass index (BMI) of 18 to 30 kg/m2, inclusive, and weighs 50 to 100 kg (110 to 220 pounds), inclusive, at screening and check-in.
7. The subject is considered to be in stable health by the investigator.
8. The subject agrees to comply with all protocol requirements.
Minimum age
18 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1.Any significant acute or chronic medical illness including history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease.
2. Vitamin A deficiency.
3. Any recent viral or bacterial infection.
4. Participated in any clinical study in last 6 weeks.
5. History of significant drug allergy
6. History of significant vision, ocular or retinal disorder.
7. Recent surgery, blood transfusion, drug or alcohol abuse and use of tobacco or nicotine containing products in past month.
8. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECGs, or clinical laboratory determinations Other protocol-defined inclusion/exclusion criteria could apply.

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
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/11/2018
Actual
15/11/2018
Date of last participant enrolment
Anticipated
Actual
20/08/2019
Date of last data collection
Anticipated
31/10/2019
Actual
16/09/2019
Sample size
Target
72
Accrual to date
Final
71
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 12318 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 24554 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 301061 0
Commercial sector/Industry
Name [1] 301061 0
RBP4 Pty Ltd
Address [1] 301061 0
58 Gipps Street, Collingwood Victoria 3066, Australia
Country [1] 301061 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
RBP4 Pty Ltd
Address
58 Gipps Street, Collingwood Victoria 3066, Australia
Country
Australia
Secondary sponsor category [1] 300669 0
None
Name [1] 300669 0
Address [1] 300669 0
Country [1] 300669 0
Other collaborator category [1] 280413 0
Commercial sector/Industry
Name [1] 280413 0
Belite Bio, Inc
Address [1] 280413 0
Ugland House
Grand Cayman, KY1-1104
Cayman Islands
Country [1] 280413 0
United Kingdom

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301815 0
Bellberry Human Research Ethics Committee H [EC00459]
Ethics committee address [1] 301815 0
129 Glen Osmond Rd Eastwood SA 5063
Ethics committee country [1] 301815 0
Australia
Date submitted for ethics approval [1] 301815 0
Approval date [1] 301815 0
24/09/2018
Ethics approval number [1] 301815 0

Summary
Brief summary
A double-blind, placebo-controlled, single ascending dose (SAD) study is planned to assess safety, pharmacokinetics (PK), and pharmacodynamics of LBS-008 in healthy adult volunteers. Healthy male or female adults with no significant ocular abnormalities will be enrolled. The plan is to enroll 40 subjects, in five cohorts of eight subjects each; additional cohorts (eight subjects per cohort) may be enrolled if it is deemed appropriate by the sponsor to repeat a dose level or to study another dose level. Within each cohort, six subjects will be randomized to receive active drug and two subjects will receive placebo. Each subject will participate in only one dose level. Subjects will receive single ascending doses of 50, 100, 200, 400, and 25 mg LBS-008 administered as 25 or 200 mg capsules, or an equivalent number of placebo capsules. Each dose cohort will be separated into two groups; a sentinel group of two subjects (one active and one placebo) will be dosed at least 24 hours before the remaining six subjects (five active and one placebo).

The MAD portion will start after the completion of Cohort 4 of SAD and will have up to 4 cohorts and up to a total of 32 subjects (8 subjects per cohort). The starting dose of LBS-008 will be 10 mg and the planned doses for subsequent cohorts are 25, 5 and 12 mg. The final doses are determined based on the outcome of SAD portion.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 88206 0
Dr Lara Hatchuel
Address 88206 0
QEII Medical Centre, First Floor, B Block Hospital Avenue, Nedlands, Western Australia, 6009, Australia
Country 88206 0
Australia
Phone 88206 0
+61 0424686547
Fax 88206 0
Email 88206 0
lhatchuel@linear.org.au
Contact person for public queries
Name 88207 0
Dr Lara Hatchuel
Address 88207 0
QEII Medical Centre, First Floor, B Block Hospital Avenue, Nedlands, Western Australia, 6009, Australia
Country 88207 0
Australia
Phone 88207 0
+61 0424686547
Fax 88207 0
Email 88207 0
lhatchuel@linear.org.au
Contact person for scientific queries
Name 88208 0
Miss Yvonne Chen
Address 88208 0
RBP4 Pty Ltd
58 Gipps Street, Collingwood Victoria 3066, Australia
Country 88208 0
Australia
Phone 88208 0
+61 3 94197607
Fax 88208 0
Email 88208 0
yvonnechen@linbioscience.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
IPD will not be available.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary