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Trial registered on ANZCTR


Registration number
ACTRN12618001461280
Ethics application status
Approved
Date submitted
27/07/2018
Date registered
30/08/2018
Date last updated
18/03/2020
Date data sharing statement initially provided
22/08/2019
Date results information initially provided
22/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Single Ascending Dose Study to Evaluate the Safety and Tolerability of LPT99 Administered to Healthy Adult Subjects
Scientific title
A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study
to Evaluate the Safety and Tolerability of LPT99 Administered to Healthy Adult Subjects
Secondary ID [1] 295608 0
SP01-C-18
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prevention of Hearing loss 308931 0
Condition category
Condition code
Ear 307832 307832 0 0
Other ear disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will be performed at a single investigational site in Australia.
There are Four (4) sequential doses: 25 µg (200 µM), 50 µg (400 µM), 75 µg (600 µM) and 100 µg (797 µM). Approximately 32 healthy male and female subjects with normal baseline
hearing will be enrolled for the study, and each dose cohort will be having 8 subjects.
Only 1 ear will be treated in an individual subject; the other ear will serve as the control ear for that subject. Each cohort will follow a sentinel dosing approach, in which 1 active and 1 placebo subject will be dosed at least 24 hours prior to the remaining subjects in the cohort.
Mode of administration is transtympanic and strategies used to monitor adherence to the intervention is syringe accountability, unblinded pharmacy CRA, direct observation.
Intervention code [1] 301907 0
Treatment: Drugs
Comparator / control treatment
Matching placebo (hydrogel vehicle) administered transtympanic(TT).
Control group
Placebo

Outcomes
Primary outcome [1] 306809 0
The primary objective of this study is to investigate the safety and tolerability of single ascending doses of LPT99 when administered transtympanically to healthy adult subjects.
Timepoint [1] 306809 0
The safety and tolerability will be evaluated by targeted physical examination,
including direct otoscopic examination; vital signs, audiogram and tympanogram; electrocardiogram (ECG); and evaluation of adverse events (AEs) and safety laboratory parameters compared with pretreatment evaluations.
timepoint/s of assessment of this outcome: these assessments will be performed at all study visits. Subjects will be followed up until Day 30 post dose.
Secondary outcome [1] 349708 0
The secondary objective of this study is to evaluate systemic exposure of ascending doses of LPT99 when administered transtympanically to healthy adult subjects.
This is a single measure – PK.

Since LPT99 will be administered TT locally to the middle ear, significant systemic detection of LPT99 is not anticipated. Limited PK sampling is incorporated to assess systemic exposure. So no PK parameters are planned now.
Timepoint [1] 349708 0
The planned doses will be 25 µg (200 µM), 50 µg (400 µM), 75 µg (600 µM) and 100 µg
(797 µM); all doses will be administered in a volume of 0.2 mL liquid hydrogel matrix. At each dose, 6 subjects will be randomized to receive LPT99, and 2 subjects will be randomized to receive matching placebo. All subjects will remain under observation overnight at the study site after receiving study drug or placebo, to allow for PK sample collection and AE assessment. Blood samples for plasma pharmacokinetic (PK) analysis will be obtained to determine the levels of LPT99 in systemic circulation.

PK samples will be collected at the Day -1 visit and at 2, 4, 12 and 24hrs post-treatment on Day 1. Single PK samples will be obtained at all subsequent scheduled visits (Visits 3 through 5).

Eligibility
Key inclusion criteria
1. Male or female subject, age 18 to 65 years (inclusive) at Screening
2. Provides written informed consent prior to participation in any study procedure
3. Normal hearing, defined as is greater than or equal to 20 dB from 250 Hz to 8 kHz bilaterally
4. Normal tympanogram
5. No known allergies to lidocaine or prilocaine local anesthesia, to EMLA® (lidocaine
2.5% and prilocaine 2.5%) cream, or to phenol
6. Female subjects of childbearing potential, must not be pregnant, lactating, or planning
a pregnancy, must have a negative pregnancy test at screening and at Day -1, and
must use a medically acceptable method of contraception [e.g., intrauterine device
(IUD), intrauterine system (IUS), or hormonal contraception (oral, implant, or
injectable) begun >30 days prior to screening]. Acceptable contraceptive options may
also include abstinence (if this is the preferred lifestyle for the participant), physical
relationship with a same-sex partner or a partner who has had a vasectomy at least 6
months prior to Screening. Subjects must agree to adhere to contraceptive measures
from screening through 30 days after study drug administration.
7. Male subjects must be surgically sterile (vasectomy at least 6 months prior to
screening) or practice acceptable methods of contraception, and must agree to abstain
from sperm donation, from study drug administration through 90 days after
administration of study drug. Male subjects must agree to use a condom to protect
male and female partners from exposure to study drug. Male subjects with female
partners of childbearing potential, must also agree to partner use of hormonal
contraception (oral, implant, or injection), an IUD, or an IUS. Complete abstinence
from sexual intercourse, if this is the preferred lifestyle for the participant, is an
acceptable contraceptive option.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Bleeding disorder that could affect the TT study drug administration
2. Use of anticoagulant medication within 30 days prior to screening.
3. History of surgery to the inner ear
4. History of chronic tinnitus or Meniere's disease
5. History of radiation therapy to the head or neck
6. History of chronic middle ear infection, endolymphatic sac surgery
7. History of known hypersensitivity to any components of the study drug or formulation
8. Positive alcohol or urine drug test at Screening or on Study Day -1
9. Positive pregnancy test at Screening or on study Day -1
10. Acute illness or history of illness, that, in the opinion of the Investigator, could pose a
threat to or harm the subject, or obscure interpretation of laboratory test results or
study data
11. Acute respiratory infection, acute nasopharyngitis, sinusitis, chronic cough, or
symptoms of allergic rhinitis
12. Any clinically significant abnormalities on Screening or Day -1 laboratories, as
determined by the Investigator
13. Abnormality of tympanic membrane (perforation, retraction, history of any ear
surgery, effusion or other middle ear pathology) that would preclude TT
administration
14. Received study drug or placebo in another clinical study within the 30 days prior to
study drug administration
15. Deemed unsuitable for study participation by the Investigator, based on the
Investigator's judgment

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

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

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/10/2018
Actual
25/09/2018
Date of last participant enrolment
Anticipated
29/01/2019
Actual
20/05/2019
Date of last data collection
Anticipated
20/09/2019
Actual
24/09/2019
Sample size
Target
32
Accrual to date
Final
33
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 300182 0
Commercial sector/Industry
Name [1] 300182 0
Spiral Therapeutics, Inc.
Country [1] 300182 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Spiral Therapeutics, Inc.
Address
1000 Marina Boulevard, Suite 105, Brisbane, California 94005
Country
United States of America
Secondary sponsor category [1] 299593 0
None
Name [1] 299593 0
Address [1] 299593 0
Country [1] 299593 0
Other collaborator category [1] 280255 0
Commercial sector/Industry
Name [1] 280255 0
Novotech (Australia) Pty Limited
Address [1] 280255 0
Level 3, 235 Pyrmont Street, Pyrmont NSW 2009
Country [1] 280255 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301014 0
Bellberry Human Research Ethics
Ethics committee address [1] 301014 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [1] 301014 0
Australia
Date submitted for ethics approval [1] 301014 0
04/07/2018
Approval date [1] 301014 0
28/08/2018
Ethics approval number [1] 301014 0

Summary
Brief summary
This is a randomized, double-blind, placebo-controlled, parallel-group, single ascending dose study in healthy subjects.
LPT99, the study drug is an Apaf1 inhibitor that can permeate the cochlea. LPT99 is being developed as a locally administered otoprotective agent that would specifically block apoptosis in the ear without interfering with anti-tumor activity of the platinum-based chemotherapeutic agent delivered systemically.
There are four sequential doses: 25 µg (200 µM), 50 µg (400 µM), 75 µg (600 µM) and
100 µg (797 µM). Approximately 32 healthy male and female subjects with normal baseline
hearing will be enrolled, with 8 subjects planned for each dose cohort. Each Subject will receive a dose of LPT99 or matching placebo by transtympanic (TT) administration. In all subjects, study drug will be unilaterally delivered (ie, 1 ear will remain untreated, serving as the control ear for that subject). The study will include sentinel subjects in the initial cohort and all subsequent dose escalation cohorts.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 85606 0
Dr Ana Liza Sun
Address 85606 0
Linear Clinical Research, 1 Hospital Avenue, B-Block, 1st Floor, Nedlands, Australia, Western Australia (WA)- 6009
Country 85606 0
Australia
Phone 85606 0
+61 8 6382 5100
Fax 85606 0
Email 85606 0
[email protected]
Contact person for public queries
Name 85607 0
Mr Hugo Peris
Address 85607 0
Spiral Therapeutics Inc, 1000 Marina Boulevard, Suite 105, Brisbane, California 94005
Country 85607 0
United States of America
Phone 85607 0
+16504530893
Fax 85607 0
Email 85607 0
[email protected]
Contact person for scientific queries
Name 85608 0
Mr Hugo Peris
Address 85608 0
Spiral Therapeutics Inc, 1000 Marina Boulevard, Suite 105, Brisbane, California 94005
Country 85608 0
United States of America
Phone 85608 0
+16504530893
Fax 85608 0
Email 85608 0
[email protected]

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
SourceTitleYear of PublicationDOI
EmbaseHearing loss drug discovery and medicinal chemistry: Current status, challenges, and opportunities.2022https://dx.doi.org/10.1016/bs.pmch.2022.05.001
N.B. These documents automatically identified may not have been verified by the study sponsor.