Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001122741
Ethics application status
Approved
Date submitted
10/08/2022
Date registered
16/08/2022
Date last updated
23/03/2023
Date data sharing statement initially provided
16/08/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1 study to look at the safety of an intranasal formulation of an MRI contrast agent in healthy adults
Scientific title
A Phase 1 Open-Label, Randomised Study of the Safety, Tolerability and Brain Delivery of Intranasal INB-01 in Healthy Adult Participants
Secondary ID [1] 307702 0
INB-01-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
MRI imaging for diagnostic purposes 327258 0
Condition category
Condition code
Public Health 324394 324394 0 0
Other public health

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Approximately 12 healthy men or women will be enrolled into this study. They will be randomised in a 1:5 fashion between the two stages of the study.


In Stage 1, 2 healthy men and women will receive a single intranasal dose of placebo. The dose is divided into 2 sprays per nostril. Each spray is 140 µL for a total volume per nostril of 280 µL and a total overall volume per dose of 560 µL. The dose will be administered by a doctor. The participants will be observed in the clinic for 4 hours.

If there are no tolerability concerns in Stage 1, then 10 healthy men and women in Stage 2 will receive a single intranasal 37 mg dose of INB-01 which is an intranasal form of gadolinium, an active contrast agent. The dose is divided into 2 sprays per nostril. Each spray is 140 µL for a total volume per nostril of 280 µL and a total overall volume per dose of 560 µL. The dose will be administered by a doctor. The participants will be observed in the clinic for 6 hours during which time they will have 5 MRI scans of the brain conducted by a radiologist.
Intervention code [1] 324180 0
Diagnosis / Prognosis
Comparator / control treatment
Placebo control group. Placebo is an intranasal polyoxamer formulation that does not contain the active INB-01
Control group
Placebo

Outcomes
Primary outcome [1] 332203 0
To evaluate the safety and tolerability of an intranasal dose of INB-01 Intranasal Solution in healthy adult participants through the composite assessment of: treatment-emergent adverse events assessed through regular solicitation of participants and review of physical examination data, nasal examination data collected using a nasal speculum, vital sign data including blood pressure measured using a digital blood pressure monitor, heart rate measured as beats per minute, temperature assessed using a digital thermometer and respiratory rate measured using a manual counting of breaths per minute, ECG data, clinical laboratory assessments of blood and urine: hematology (standard panel), chemistry (standard panel) and urinalysis (standard panel), nasal symptoms assessed through a questionnaire, changes in a participants ability to smell assessed through a smell identification test, and tolerability of the intranasal dose assessed from a visual analogue scale of tolerability and a questionnaire on nasal symptoms that was designed for use in the study.
Timepoint [1] 332203 0
Treatment emergent adverse events and serious adverse events will be collected from the start of dosing through the end of study visit on Day 8.
Physical and nasal examination will be conducted at screening and prior to discharge from the clinic on Day 1. (4 hours post dose in Stage 1 and 6 hours post dose in Stage 2)
Vital signs will be measured at screening and on Day 1 prior to dosing and then post dose and prior to discharge from the clinic (30 minutes, 2 hours and 4 hours post dose in Stage 1 and 2 hours, 4 hours and 6 hours post dose in Stage 2).
ECG data will be collected and on Day 1 prior to dosing and then prior to discharge from the clinic (4 hours post dose in Stage 1 and 6 hours post dose in Stage 2).
Clinical laboratory assessment of blood and urine will be collected at screening and prior to discharge from the clinic on Day 1 (4 hours post dose in Stage 1 and 6 hours post dose in Stage 2)
The nasal symptom questionnaire will be completed at screening, on Day 1 prior to dosing and then post dose and prior to discharge from the clinic (2 hours and 4 hours post dose in Stage 1 and 2 hours and 6 hours post dose in Stage 2).
The smell identification test will be conducted at screening and prior to discharge from the clinic on Day 1.(4 hours post dose in Stage 1 and 6 hours post dose in Stage 2)
The tolerability questionnaire will be completed after dosing and prior to discharge from the clinic on Day 1. (30 minutes, 2 hours and 4 hours post dose in Stage 1 and 15 minutes, 2 hours, 4 hours and 6 hours post dose in Stage 2).
Secondary outcome [1] 412525 0
To quantify the delivery of gadolinium in different areas of the brain following a single intranasal dose of INB-01 by measuring the contrast levels from MRI scans
Timepoint [1] 412525 0
MRI scans will be conducted prior to dosing and at 30 minutes, 1 hour, 3 hours and 5 hours after dosing on Day 1
Secondary outcome [2] 412526 0
To assess the amount of gadolinium in blood after a single intranasal dose of INB-01
Timepoint [2] 412526 0
Blood samples will be collected at screening (Stage 1 and Stage 2) and then prior to discharge from the clinic on Day 1 (Stage 2 at 6 hours post dose)
Secondary outcome [3] 412792 0
To assess the amount of gadolinium in urine after a single intranasal dose of INB-01
Timepoint [3] 412792 0
Urine will be collected at screening (Stage 1 and Stage 2) and prior to discharge from the clinic on Day 1 (Stage 2 at 6 hours post dose)

Eligibility
Key inclusion criteria
1. Participants must be:
a. Of non-childbearing potential, or
b. If of childbearing potential, be non-pregnant and not lactating and agree to use highly effective contraception, not become pregnant and not donate eggs from screening through 30 days post dose, or
c. If male, if engaging in sexual intercourse with a partner of childbearing potential, must be willing to use highly effective contraception from screening through 30 days post-last dose and agree not to donate sperm during this period.
2. Judged to be in good health based on medical history, physical examination, vital sign measurements, and laboratory safety tests performed at the screening visit and/or before first dose.
3. Has a body mass index (BMI) between 18.0 and 32.0 kg/m2 with a weight greater than or equal to 50 kg at time of screening.
4. Agrees to be available for all study visits and cooperate fully with the requirements of the study protocol, including the schedule of assessments.
5. Willing and able to provide written informed consent.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Has a deformity of the nasal cavity, a known deviation of the nasal septum; current symptoms of hay fever, acute or chronic sinusitis or recent history of surgery of the nasal cavity and/or nasopharynx, atrophic rhinitis or a history or presence of any anatomical or medical condition that might impede delivery or absorption of the intranasal investigational product.
2. Use of intranasal medication in the 4 weeks prior to Day 1,
3. Has received a previous dose of gadolinium-based contrast agent in their lifetime
4. Has an active malignancy, or history of malignancy, excluding basal or squamous cell carcinoma of the skin, within 2 years prior to screening.
5. Has a history of cardiovascular, cerebrovascular, or peripheral vascular disease, including, but not limited to, unstable angina, myocardial infarction, congestive heart failure, cardiac arrhythmia, hypertension, hypotension, bradycardia, or tachycardia.
6. Has a clinically significant history or presence of electrocardiogram findings at screening.
7. Has clinically significant laboratory abnormalities,
8. Current symptomatic seasonal allergic rhinitis (hayfever).
9. History of severe allergy or anaphylaxis to any drug, food, toxin or other exposure.
10. History of moderate or severe substance abuse within 5 years prior to screening.
11. History of alcohol abuse within 5 years prior to screening.
12. Positive test results for hepatitis B surface antigen, hepatitis B core antibodies, hepatitis C virus antibody, and human immunodeficiency virus (HIV) p24 antigen and HIV type 1 and type 2 antibodies at screening
13. Smoked any tobacco or related products within 3 months prior to dosing,
14. With the exception of oral contraceptives or hormone replacement therapy, is taking over-the-counter or prescription medications or herbal, nutritional or dietary supplements.
15. Received treatment with another investigational drug, investigational device, or approved therapy for investigational use within 30 days or 5 half-lives (whichever is longer) prior to dosing
16. Has donated blood or plasma within 30 days prior to screening or has had a loss of whole blood of more than 500 mL within the 30 days prior to screening, or receipt of a blood transfusion within one year prior to screening.
17. Has experienced acute upper respiratory illness including a common cold, within 14 days prior to screening or baseline visits.
18. Unable to undergo MRI scanning due to the presence of non-removable metal implants, claustrophobia or any other contraindication
19. Other unspecified reasons that, in the opinion of the PI or Sponsor, make the participant unsuitable for enrollment.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computer generated simple randomisation sequence
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety
Statistical methods / analysis
This is an exploratory study and therefore it is not powered for inferential statistical analyses. This study will enrol approximately 2 participants in Stage 1 and 10 participants in Stage 2.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Data needed was collected
Date of first participant enrolment
Anticipated
1/12/2022
Actual
28/11/2022
Date of last participant enrolment
Anticipated
17/01/2023
Actual
9/12/2022
Date of last data collection
Anticipated
31/01/2023
Actual
15/12/2022
Sample size
Target
12
Accrual to date
Final
7
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 22903 0
University of Queensland - St Lucia
Recruitment postcode(s) [1] 38211 0
4072 - St Lucia

Funding & Sponsors
Funding source category [1] 311971 0
Commercial sector/Industry
Name [1] 311971 0
InnarisBio Australia Pty Ltd
Country [1] 311971 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
InnarisBio Australia Pty Ltd
Address
58 Gipps Street
Collingwood, VIC 3066
Country
Australia
Secondary sponsor category [1] 313459 0
None
Name [1] 313459 0
Address [1] 313459 0
Country [1] 313459 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311400 0
Bellberry Limited Human Research Ethics Committee
Ethics committee address [1] 311400 0
Ethics committee country [1] 311400 0
Australia
Date submitted for ethics approval [1] 311400 0
24/08/2022
Approval date [1] 311400 0
04/10/2022
Ethics approval number [1] 311400 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120962 0
A/Prof Ben Wallwork
Address 120962 0
School of Pharmacy
The University of Queensland
Pharmacy Australia Centre of Excellence
20 Cornwall St,
Woolloongabba QLD 4102
Country 120962 0
Australia
Phone 120962 0
+61 7 3847 9988
Fax 120962 0
Email 120962 0
[email protected]
Contact person for public queries
Name 120963 0
Harendra Parekh
Address 120963 0
School of Pharmacy
The University of Queensland
Pharmacy Australia Centre of Excellence
20 Cornwall St,
Woolloongabba QLD 4102
Country 120963 0
Australia
Phone 120963 0
+61 7 3346 1887
Fax 120963 0
Email 120963 0
[email protected]
Contact person for scientific queries
Name 120964 0
Harendra Parekh
Address 120964 0
School of Pharmacy
The University of Queensland
Pharmacy Australia Centre of Excellence
20 Cornwall St,
Woolloongabba QLD 4102
Country 120964 0
Australia
Phone 120964 0
+61 7 3346 1887
Fax 120964 0
Email 120964 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
Only aggregate participant data will be available from this study.


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.