Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000816954
Ethics application status
Approved
Date submitted
4/08/2020
Date registered
14/08/2020
Date last updated
28/06/2021
Date data sharing statement initially provided
14/08/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A Double-blinded, Randomised, and Placebo-controlled Safety Study of AT-301 Nasal Spray in Healthy Adults
Scientific title
A Double-blinded, Randomised, and Placebo-controlled Safety Study of AT-301 Nasal Spray in Healthy Adults
Secondary ID [1] 301936 0
NIL
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 318316 0
Condition category
Condition code
Respiratory 316325 316325 0 0
Other respiratory disorders / diseases
Infection 316627 316627 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomised to one of the four cohorts only.

AT-301 Nasal Spray
Part 1 maximum exposure - 0.4 mL total (single dose)
Each spray is metered to 0.1 mL, and a single dose is to be administered in Part 1.

Part 1 has Cohort 1 and Cohort 2. Participants in Cohort 1 will receive 1 spray per nostril and Participants in Cohort 2 will receive 2 sprays per nostril.

Participants will receive one or two sprays into each nostril once only.

Part 2 maximum exposure - 16.8 mL total (over 14 days)

Each spray is metered to 0.1 mL, and is to be taken 3 times a day.

Part 2 consists of Cohort 3 and Cohort 4. Participants in Cohort 3 will receive 1 spray per nostril and participants in Cohort 4 will receive 2 sprays per nostril

Participants will receive one or two sprays per nostril three times a day for 14 days.
Adherence will be monitored via diary / report.
Intervention code [1] 318127 0
Treatment: Drugs
Comparator / control treatment
Placebo (Composition):
Sodium Chloride
Benzalkonium Chloride (preservative)
NaOH/HCl
Purified Water
Control group
Placebo

Outcomes
Primary outcome [1] 324493 0
To evaluate the safety and tolerability of single and multiple doses of AT-301 administered via nasal instillation to healthy volunteers. These will be assessed through:
1. Change from baseline in clinical laboratory parameters (serum chemistry, haematology,
coagulation, urinalysis by blood and urine laboratory tests
2. Change from baseline in vital signs parameters through blood pressure, heart rate, temperature measurements.
3. Change from baseline in 12-Lead ECGs by ECG machine
4. Change from baseline in physical examination by examination by doctor
5. Change from baseline in oxygen saturation by oximeter
6. Adverse event reporting including relatedness to study drug and intensity of the event. These will be assessed by study staff in person visits and by telephone as well as recorded in patient diaries.
7. Macroscopic nasal examinations by clinical examination
Timepoint [1] 324493 0
- Pre-treatment at Baseline visit
- After treatment at End of Study Visit on Day 4 for Part 1, and Day 17 for Part 2
Secondary outcome [1] 384808 0
To assess the immediate attributes of AT-301 nasal spray by participant using a Nasal Attributes Questionnaire designed for this study
Timepoint [1] 384808 0
After treatment at End of Study Visit on Day 4 for Part 1, and Day 17 for Part 2
Secondary outcome [2] 384809 0
To assess the incidence and severity of bronchospasm following administration of AT-301 via nasal instillation through direct observation
Timepoint [2] 384809 0
Immediately after dosing with a single dose (Part 1: Cohorts 1 and 2)

Immediately after dosing on Days 1,2,7, and 14 (Part 2: Cohorts 3 and 4)

Eligibility
Key inclusion criteria
Healthy volunteers will be included in the study if they meet all of the following criteria:
1. Must have given written informed consent before any study-related activities are carried
out and must be able to understand the full nature and purpose of the trial, including
possible risks and adverse effects
2. Adult males and females, 18 to 64 years of age (inclusive) at the screening visit
3. Are non-smokers (including tobacco, e-cigarettes and marijuana) for a minimum of 1
month prior to the screening visit. Non-smokers with a significant history of smoking (> 5
pack years) are not eligible
4. Have a physically normal nasal structure (minor septum deviation allowable)
5. Body mass index (BMI) (calculated) within the range of 18 to 30 kg/m2 inclusive at the
screening visit, and prior to dosing
6. Medically healthy without clinically significant abnormalities in the opinion of the
investigator at the screening visit and prior to dosing on Day 1, including:
a. Physical examination without any clinically significant findings
b. Systolic blood pressure (BP) in the range of 90 to 140 mm Hg (inclusive) and diastolic BP
in the range of 50 to 90 mm Hg (inclusive) after at least 5 minutes in a seated position
c. Heart rate (HR) in the range of 45 to 100 beats/min (inclusive) after at least 5 minutes rest
in a semi-recumbent position
d. Normal body (tympanic) temperature (35.5.to 37.7°C, inclusive)
e. The 12-lead electrocardiogram (ECG), taken after the volunteer has been supine for at
least 5 minutes, must be within normal range (corrected QT interval [QTc] males less than
or equal to 450 msec; females less than or equal to 470 msec) or with abnormalities that
are not hazardous to the volunteer according to the opinion of the Investigator
f. No clinically significant findings in serum chemistry, haematology, coagulation and
urinalysis examinations as judged by the Investigator at screening
7. Negative cotinine, drug and alcohol tests at screening and prior to dosing on Day 1
8. Female volunteers must:
a. Be of non-child-bearing potential i.e., have follicle-stimulating hormone levels >40 IU/L
at screening and be 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), or
b. If of childbearing potential, must have a negative pregnancy test at Screening (blood
test) and before the first study drug administration (pre-dose Day 1 urine test). They must
agree not to attempt to become pregnant, must not donate ova, and must agree to use 2
forms of highly effective contraceptive method for penile-vaginal intercourse from
signing consent until at least 30 days after the last dose of study therapy
9. Male volunteers, if not surgically sterilised, must agree not to donate sperm and if
engaging in sexual intercourse with a female partner who could become pregnant, must
agree to use a condom in addition to having the female partner use a highly effective
contraceptive method from signing the consent form until at least 64 days after the last
dose of study therapy
10. Have suitable venous access for blood sampling
11. Willing and able to comply with the requirements of the study protocol
Minimum age
18 Years
Maximum age
64 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Healthy volunteers will be excluded from the study if there is evidence of any of the following at screening or prior to dosing on Day 1:
1. History or presence of the following based on self-report: of tuberculosis, asthma
(including childhood asthma), severe bronchial asthma, chronic obstructive pulmonary
disease, peptic ulcer or major pulmonary airway disease
2. Previous diagnoses of nasal polyps or any ear, nose and throat pathology deemed by the
Investigator to affect assessment of the investigational product
3. Active hay fever, rhinitis or cold
4. History or presence of significant cardiovascular, hepatic, renal, haematological,
gastrointestinal, endocrine, immunologic, dermatologic, neurological or psychiatric
disease, including any acute illness or surgery within the past three months determined
by the PI to be clinically relevant
5. Known allergy to any of the formula components
6. Current obstructive pneumonia, severe pulmonary interstitial fibrosis, alveolar proteinosis
and allergic alveolitis caused by lung tumour
7. Positive serum pregnancy test for women of childbearing potential at the Screening visit
or positive urine pregnancy test with confirmatory serum pregnancy test prior to dosing
on Day 1
8. Females who are breastfeeding
9. Liver function test results (i.e., aspartate aminotransferase [AST], alanine
aminotransferase [ALT], and gamma-glutamyl transferase [GGT]) and total bilirubin < 1.5 x
fold above the upper limit of normal at the screening visit. Elevated total bilirubin
allowable if an isolated finding
10. Positive testing for active human immunodeficiency virus (HIV), hepatitis B surface
antigen (HBsAg), hepatitis C virus (HCV) antibodies, at the screening visit
11. Use of any prescription or over-the-counter medication (including herbal products, diet
aids, and hormone supplements) within 10 days or 5 half-lives of the medication
(whichever is longer) prior to the first study drug administration, except for
contraceptives for female participants of childbearing potential and occasional use of
paracetamol
12. Donation of blood or plasma within 30 days prior to randomization, or loss of whole
blood of more than 500 mL within 30 days prior to randomization, or receipt of a blood
transfusion within 1 year of study enrolment
13. Participation in another investigational clinical trial within 60 days or 5 half-lives
(whichever is longer) in the case of an investigational drug prior to the first drug
administration
14. Any other condition or prior therapy, which, in the opinion of the Investigator, would
make the volunteer unsuitable for this study, including unable to cooperate fully with the
requirements of the study protocol or likely to be non-compliant with any study
requirements

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
17/08/2020
Actual
17/08/2020
Date of last participant enrolment
Anticipated
Actual
16/10/2020
Date of last data collection
Anticipated
Actual
1/11/2020
Sample size
Target
32
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 306236 0
Commercial sector/Industry
Name [1] 306236 0
Atossa Therapeutics Inc
Country [1] 306236 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Atossa Therapeutics Inc
Address
107 Spring Street
Seattle, WA, 98104
Country
United States of America
Secondary sponsor category [1] 306718 0
Commercial sector/Industry
Name [1] 306718 0
Avance Clinical Pty Ltd
Address [1] 306718 0
Level 1, 2 Ann Nelson drive
Thebarton 5031, South Australia
Country [1] 306718 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306446 0
Bellberry HREC
Ethics committee address [1] 306446 0
Ethics committee country [1] 306446 0
Australia
Date submitted for ethics approval [1] 306446 0
Approval date [1] 306446 0
31/07/2020
Ethics approval number [1] 306446 0

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

Contacts
Principal investigator
Name 103906 0
Dr Emir Redzepagic
Address 103906 0
CMAX Clinical Research
Level 5/18a North Terrace, Adelaide SA 5000
Country 103906 0
Australia
Phone 103906 0
+61 08 7088 7900
Fax 103906 0
Email 103906 0
[email protected]
Contact person for public queries
Name 103907 0
Heather Fraser
Address 103907 0
Atossa Therapeutics
107 Spring St
Seattle, WA 98104
Country 103907 0
United States of America
Phone 103907 0
+1 650 996 2622
Fax 103907 0
Email 103907 0
[email protected]
Contact person for scientific queries
Name 103908 0
Heather Fraser
Address 103908 0
Atossa Therapeutics
107 Spring St
Seattle, WA 98104
Country 103908 0
United States of America
Phone 103908 0
+1 650 996 2622
Fax 103908 0
Email 103908 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
No additional documents have been identified.